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1

Kulmala, Juha-Pekka, Marko T. Korhonen, Sami Kuitunen, Harri Suominen, Ari Heinonen, Aki Mikkola, and Janne Avela. "Which muscles compromise human locomotor performance with age?" Journal of The Royal Society Interface 11, no. 100 (November 6, 2014): 20140858. http://dx.doi.org/10.1098/rsif.2014.0858.

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Анотація:
Ageing leads to a progressive decline in human locomotor performance. However, it is not known whether this decline results from reduced joint moment and power generation of all lower limb muscle groups or just some of them. To further our understanding of age-related locomotor decline, we compare the amounts of joint moments and powers generated by lower limb muscles during walking (self-selected), running (4 m s −1 ) and sprinting (maximal speed) among young, middle-aged and old adults. We find that age-related deficit in ankle plantarflexor moment and power generation becomes more severe as locomotion change from walking to running to sprinting. As a result, old adults generate more power at the knee and hip extensors than their younger counterparts when walking and running at the same speed. During maximal sprinting, young adults with faster top speeds demonstrate greater moments and powers from the ankle and hip joints, but interestingly, not from the knee joint when compared with the middle-aged and old adults. These findings indicate that propulsive deficit of ankle contributes most to the age-related locomotor decline. In addition, reduced muscular output from the hip rather than from knee limits the sprinting performance in older age.
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2

Studholme, Keith M., Heinrich S. Gompf, and Lawrence P. Morin. "Brief light stimulation during the mouse nocturnal activity phase simultaneously induces a decline in core temperature and locomotor activity followed by EEG-determined sleep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 304, no. 6 (March 15, 2013): R459—R471. http://dx.doi.org/10.1152/ajpregu.00460.2012.

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Light exerts a variety of effects on mammals. Unexpectedly, one of these effects is the cessation of nocturnal locomotion and the induction of behavioral sleep (photosomnolence). Here, we extend the initial observations in several ways, including the fundamental demonstration that core body temperature (Tc) drops substantially (about 1.5°C) in response to the light stimulation at CT15 or CT18 in a manner suggesting that the change is a direct response to light rather than simply a result of the locomotor suppression. The results show that 1) the decline of locomotion and Tc begin soon after nocturnal light stimulation; 2) the variability in the magnitude and onset of light-induced locomotor suppression is very large, whereas the variability in Tc is very small; 3) Tc recovers from the light-induced decline in advance of the recovery of locomotion; 4) under entrained and freerunning conditions, the daily late afternoon Tc increase occurs in advance of the corresponding increase in wheel running; and 5) toward the end of the subjective night, the nocturnally elevated Tc persists longer than does locomotor activity. Finally, EEG measurements confirm light-induced sleep and, when Tc or locomotion was measured, show their temporal association with sleep onset. Both EEG- and immobility-based sleep detection methods confirm rapid induction of light-induced sleep. The similarities between light-induced loss of locomotion and drop in Tc suggest a common cause for parallel responses. The photosomnolence response may be contingent upon both the absence of locomotion and a simultaneous low Tc.
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3

Hewitt, Victoria L., Leonor Miller-Fleming, Madeleine J. Twyning, Simonetta Andreazza, Francesca Mattedi, Julien Prudent, Franck Polleux, Alessio Vagnoni та Alexander J. Whitworth. "Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity". Life Science Alliance 5, № 11 (13 липня 2022): e202201531. http://dx.doi.org/10.26508/lsa.202201531.

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Mitochondria-ER contact sites (MERCs) orchestrate many important cellular functions including regulating mitochondrial quality control through mitophagy and mediating mitochondrial calcium uptake. Here, we identify and functionally characterize the Drosophila ortholog of the recently identified mammalian MERC protein, Pdzd8. We find that reducing pdzd8-mediated MERCs in neurons slows age-associated decline in locomotor activity and increases lifespan in Drosophila. The protective effects of pdzd8 knockdown in neurons correlate with an increase in mitophagy, suggesting that increased mitochondrial turnover may support healthy aging of neurons. In contrast, increasing MERCs by expressing a constitutive, synthetic ER–mitochondria tether disrupts mitochondrial transport and synapse formation, accelerates age-related decline in locomotion, and reduces lifespan. Although depletion of pdzd8 prolongs the survival of flies fed with mitochondrial toxins, it is also sufficient to rescue locomotor defects of a fly model of Alzheimer’s disease expressing Amyloid β42 (Aβ42). Together, our results provide the first in vivo evidence that MERCs mediated by the tethering protein pdzd8 play a critical role in the regulation of mitochondrial quality control and neuronal homeostasis.
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4

GHIDERSA, Mădălina, Diana MOCANU, Mădălina ROBEA, Gabriel PLAVAN, Iuliana LUCA, Alin CIOBICĂ, and Ioannis MAVROUDIS. "Behavioural and Metabolical Changes Associated with the Pathophysiology of Alzheimer’s Disease in Zebrafish." Annals of the Academy of Romanian Scientists Series on Biological Sciences 10, no. 2 (2021): 66–78. http://dx.doi.org/10.56082/annalsarscibio.2021.2.66.

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Affecting 60% of the people diagnosed with dementia, Alzheimer’s disease is a neurodegenerative pathology that negatively impacts the cognitive function. It is characterised by symptoms as memory loss, locomotor difficulties, behavioural changes, and even rationalization issues. This disease has been studied on both rodents and fishes. Rodents helped science people establish the basic neurobiology of dementia, while fishes (Danio rerio – the zebra fish, especially) were more appropriate as transgenic models. Recent studies proved that transgenically induced Alzheimer’s disease at zebra fishes is not defined only by cognitive decline but also by motor function disorders. Objectives. This study aims to analyse how iron chloride and sucrose impact zebra fishes’ locomotion and memory by using the T maze. Methods. 50 zebra fishes were purchased from a local pisciculturist and randomly divided in 4 experimental groups. They were accommodated in the Ecotoxicology laboratory at “Alexandru Ioan Cuza” University for 3 weeks according to the European Union Commission and European Union Council recommendations regarding experimental purposes animals' protection and accommodation. Fishes’ possible behavioural changes were analysed after they were given sucrose and iron chloride separately and in their combination. Results. We observed that sucrose administration negatively impacted the locomotory activity while iron chloride surprisingly increased it. The possible explanation is the fact that iron chloride generated anxiety - an early-stage Alzheimer's disease symptom, and therefore improved fishes' swimming performance. Successive sucrose and iron chloride administration also led to increased locomotor activity.
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5

Richert, Laura, Mathilde Brault, Patrick Mercié, Frédéric-Antoine Dauchy, Mathias Bruyand, Carine Greib, François Dabis, Fabrice Bonnet, Geneviève Chêne, and Patrick Dehail. "Decline in locomotor functions over time in HIV-infected patients." AIDS 28, no. 10 (June 2014): 1441–49. http://dx.doi.org/10.1097/qad.0000000000000246.

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6

Dorfman, David, and Michael S. Saag. "Decline in locomotor functions over time in HIV-infected patients." AIDS 28, no. 10 (June 2014): 1531–32. http://dx.doi.org/10.1097/qad.0000000000000302.

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7

Kawakami, Katsuhiro, Satoshi Tanaka, Yuki Sugiyama, Noriaki Mochizuki та Mikito Kawamata. "Intrathecal morphine exacerbates paresis with increasing muscle tone of hindlimbs in rats with mild thoracic spinal cord injury but without damage of lumbar α-motoneurons". PLOS ONE 17, № 8 (15 серпня 2022): e0273095. http://dx.doi.org/10.1371/journal.pone.0273095.

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Adverse effects of morphine on locomotor function after moderate to severe spinal cord injury (SCI) have been reported; however, the effects after mild SCI without damage of lumbar α-motoneurons have not been investigated. We investigated the effects of lumbar intrathecal morphine on locomotor function after mild thoracic SCI and the involvement of classic opioid receptor activation. A mild thoracic contusive SCI was induced in adult rats at the T9-T10 spine level under sevoflurane anesthesia. We evaluated the effects of single doses of intrathecal morphine and selective μ-, δ-, and κ-opioid receptor agonists, continuous infusion of intrathecal morphine for 72 hours, and administration of physiological saline on locomotor function and muscle tone in the hindlimbs. The numbers of damaged and total α-motoneurons in the lumbar spinal cord were also investigated. Single doses of morphine aggravated residual locomotor function after SCI but did not affect functional recovery. Single doses of morphine and μ- and δ-opioid receptor agonists significantly aggravated residual locomotor function with increases in muscle tone after SCI, and the effects of the drugs were reversed by naloxone. In contrast, continuous infusion of morphine led to persistent decline in locomotor function with increased muscle tone, which was not reversed by naloxone, but did not increase the number of damaged lumbar α-motoneurons. These results indicate that a single dose of morphine at an analgesic dose transiently increases muscle tone of the hindlimbs via activation of spinal μ- and δ- opioid receptors, resulting in further deterioration of locomotor function in the acute phase of mild SCI. Our results also suggest that an increased dose of morphine with prolonged administration leads to persistent decline in locomotor function with increased muscle tone via mechanisms other than direct activation of classical opioid receptors. Morphine should be used cautiously even after mild SCI.
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8

Roda, Elisa, Erica Cecilia Priori, Daniela Ratto, Fabrizio De Luca, Carmine Di Iorio, Paola Angelone, Carlo Alessandro Locatelli, et al. "Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging." International Journal of Molecular Sciences 22, no. 12 (June 15, 2021): 6379. http://dx.doi.org/10.3390/ijms22126379.

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Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.
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9

Steffen, Teresa M., Bradley F. Boeve, Louise A. Mollinger-Riemann, and Cheryl M. Petersen. "Long-Term Locomotor Training for Gait and Balance in a Patient With Mixed Progressive Supranuclear Palsy and Corticobasal Degeneration." Physical Therapy 87, no. 8 (August 1, 2007): 1078–87. http://dx.doi.org/10.2522/ptj.20060166.

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Background and Purpose: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are slowly progressive tauopathies characterized by impaired balance, disturbances in gait, and frequent falls, among other features. Wheelchair dependence is an inevitable outcome in people with these disorders. Insufficient evidence exists regarding the effectiveness of exercise in the management of people with these disorders. This case report describes a program of exercise and long-term locomotor training, using a treadmill (both with and without body-weight support), to reduce falls and improve the balance and walking ability of a patient with mixed PSP and CBD features. Case Description: Six years after diagnosis with mixed PSP and CBD features, the client, a 72-year-old dentist, was seen for physical therapy for asymmetric limb apraxia, markedly impaired balance, and frequent falls during transitional movements. Intervention: Over a 2.5-year period, intervention included routine participation in an exercise group for people with Parkinson disease (mat exercise and treadmill training) and intermittent participation in individual locomotor training on a treadmill. The exercise group met for 1 hour, twice weekly. The individual treadmill sessions lasted 1 hour, once weekly, for two 14-week periods during the follow-up period. Outcomes: Over the 2.5-year period, fall frequency decreased, and tests of functional balance showed improved limits of stability (functional reach tests) and maintained balance function (Berg Balance Scale). Tests of walking performance showed only slight declines. A 4-wheeled walker was introduced and accepted by the client early in the intervention period. The client, with supervision, remained ambulatory with this wheeled walker in the community. Discussion: In this case report of a person with mixed PSP and CBD features, a physical therapy intervention, which included locomotor training using a treadmill and a long-term exercise program of stretching and strengthening, appears to have improved some dimensions of balance, slowed the rate of gait decline, prevented progression to wheelchair dependence, and decreased falls. Contrary to the expected decline in function, this client maintained independent mobility over a 2.5-year period. An ongoing, intensive program of exercise and locomotor training may help people with PSP and CBD maintain upright balance, decrease falls, and decrease the rate of decline of ambulation.
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10

Askew, Graham N., Federico Formenti, and Alberto E. Minetti. "Limitations imposed by wearing armour on Medieval soldiers' locomotor performance." Proceedings of the Royal Society B: Biological Sciences 279, no. 1729 (July 20, 2011): 640–44. http://dx.doi.org/10.1098/rspb.2011.0816.

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In Medieval Europe, soldiers wore steel plate armour for protection during warfare. Armour design reflected a trade-off between protection and mobility it offered the wearer. By the fifteenth century, a typical suit of field armour weighed between 30 and 50 kg and was distributed over the entire body. How much wearing armour affected Medieval soldiers' locomotor energetics and biomechanics is unknown. We investigated the mechanics and the energetic cost of locomotion in armour, and determined the effects on physical performance. We found that the net cost of locomotion ( C met ) during armoured walking and running is much more energetically expensive than unloaded locomotion. C met for locomotion in armour was 2.1–2.3 times higher for walking, and 1.9 times higher for running when compared with C met for unloaded locomotion at the same speed. An important component of the increased energy use results from the extra force that must be generated to support the additional mass. However, the energetic cost of locomotion in armour was also much higher than equivalent trunk loading. This additional cost is mostly explained by the increased energy required to swing the limbs and impaired breathing. Our findings can predict age-associated decline in Medieval soldiers' physical performance, and have potential implications in understanding the outcomes of past European military battles.
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11

Siwak, Christina T., Heather L. Murphey, Bruce A. Muggenburg, and Norton W. Milgram. "Age-dependent decline in locomotor activity in dogs is environment specific." Physiology & Behavior 75, no. 1-2 (February 2002): 65–70. http://dx.doi.org/10.1016/s0031-9384(01)00632-1.

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12

Apor, Péter, and László Babai. "Physical activity diminishes aging-related decline of physical and cognitive performance." Orvosi Hetilap 155, no. 21 (May 2014): 817–21. http://dx.doi.org/10.1556/oh.2014.29838.

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Aging-related decline of muscle force, walking speed, locomotor coordination, aerobic capacity and endurance exert prognostic impact on life expectancy. Proper use of training may diminish the aging process and it may improve the quality of life of elderly persons. This paper provides a brief summary on the impact of training on aging-related decline of physical and cognitive functions. Orv. Hetil., 2014, 155(21), 817–821.
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13

Kraimi, N., G. De Palma, J. Lu, D. Bowdish, E. Verdu, E. Sibille, T. Prevot, S. M. Collins, and P. Bercik. "A238 ABSENCE OF AGE-RELATED MEMORY DECLINE IN GERM-FREE MICE." Journal of the Canadian Association of Gastroenterology 4, Supplement_1 (March 1, 2021): 288–89. http://dx.doi.org/10.1093/jcag/gwab002.236.

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Abstract Background Age-associated deterioration of cognitive function and memory capacity occur in a variety of mammals, from humans to rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., Mol Neuropsychiatry 2019). Microbiota to brain signaling is now well established in mice, but the extent to which this influences age-related memory decline is unknown. Aims Our project aims to determine whether the intestinal microbiota contributes to age-related changes in brain function. We address the hypothesis that age-related cognitive decline is attenuated in the absence of the intestinal microbiota. Methods We studied locomotor behavior and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice. We used the Y-maze test based on a spontaneous alternations task to assess cognition, with alternation rate as a proxy of spatial working memory performance. The locomotor activity was measured using the open-field test. Results GF old mice traveled less distance (458.9 cm) than GF young mice (875.7 cm, p < 0.001) but these differences in locomotor activity did not influence spatial memory performance. Indeed, both GF old and GF young mice had an identical alternation rate of 73.3% (p > 0.05). This contrasted with the memory impairment found in old SPF mice that displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.2%, p = 0.13). Conclusions We conclude that the absence of age-related memory decline in germ-free mice is consistent with a role for the microbiota in the cognitive decline associated with aging, likely through action on the immune system, well documented in SPF mice (Thevaranjan et al., Cell Host & Microbe 2017). We propose that novel microbiota-targeted therapeutic strategies may delay or prevent the cognitive decline of aging. Funding Agencies CIHRBalsam Family Foundation
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14

Takeuchi, S., Y. Nishida, and T. Mizushima. "Decline of cardiac pump function during exercise could synchronize cardiac-locomotor rhythms." Physiotherapy 101 (May 2015): e1480-e1481. http://dx.doi.org/10.1016/j.physio.2015.03.1453.

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15

Ratto, Daniela, Federica Corana, Barbara Mannucci, Erica Cecilia Priori, Filippo Cobelli, Elisa Roda, Beatrice Ferrari, et al. "Hericium erinaceus Improves Recognition Memory and Induces Hippocampal and Cerebellar Neurogenesis in Frail Mice during Aging." Nutrients 11, no. 4 (March 27, 2019): 715. http://dx.doi.org/10.3390/nu11040715.

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Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, implicated in both poor quality of life and negative health outcomes. One central question surrounding frailty is whether phenotypic frailty is associated with the cognitive impairment during aging. Using spontaneous behavioral tests and by studying the dynamic change during aging, we demonstrated that the two form of vulnerability, locomotor and recognition memory decline, develop in parallel and therefore, integration of the motoric and cognitive evaluations are imperative. We developed an integrated frailty index based on both phenotypic and recognition memory performances. Hericium erinaceus (H. erinaceus) is a medicinal mushroom that improves recognition memory in mice. By using HPLC-UV-ESI/MS analyses we obtained standardized amounts of erinacine A and hericenones C and D in H. erinaceus extracts, that were tested in our animal model of physiological aging. Two-month oral supplementation with H. erinaceus reversed the age-decline of recognition memory. Proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunohistochemistry in the hippocampus and cerebellum in treated mice supported a positive effect of an H. erinaceus on neurogenesis in frail mice.
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16

Hu, S., L. Yang, C. Wu, and TC-Y. Liu. "Regulation of Wnt signaling by physical exercise in the cell biological processes of the locomotor system." Physiology International 106, no. 1 (March 2019): 1–20. http://dx.doi.org/10.1556/2060.106.2019.07.

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In the past decade, researches on Wnt signaling in cell biology have made remarkable progress regarding our understanding of embryonic development, bone formation, muscle injury and repair, neurogenesis, and tumorigenesis. The study also showed that physical activity can reverse age-dependent decline in skeletal muscle, preventing osteoporosis, regenerative neurogenesis, hippocampal function, cognitive ability, and neuromuscular junction formation, and the age-dependent recession is highly correlated with Wnt signaling pathways. However, how the biological processes in cell and physical activity during/following exercise affect the Wnt signaling path of the locomotor system is largely unknown. In this study, we first briefly introduce the important features of the cellular biological processes of exercise in the locomotor system. Then, we discuss Wnt signaling and review the very few studies that have examined Wnt signaling pathways in cellular biological processes of the locomotor system during physical exercise.
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17

Lin, Wei-Qi, Zhen-Kai Ngian, Tong-Wey Koh, and Chin-Tong Ong. "Altered stability of nuclear lamin-B marks the onset of aging in male Drosophila." PLOS ONE 17, no. 3 (March 24, 2022): e0265223. http://dx.doi.org/10.1371/journal.pone.0265223.

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Epigenetic alterations occur during aging, but it remains unclear what epigenetic features are associated with the onset of physiological decline in animals. Nuclear lamin-B forms the filamentous meshwork underneath the nuclear envelope, providing the structural scaffold necessary for genome organization and gene regulation. We found that reduced level of nuclear lamin-B protein coincides with the decline in locomotor activity and stress resistance in young adult male Drosophila. Ubiquitous lamin-B expression improves locomotor activity of the male flies at the expense of lower stress resistance and shorten lifespan. This observation suggests that tissue-specific expression of lamin-B may regulate different aspects of animal physiology during aging. To test this hypothesis, specific GAL-4 lines were used to drive the expression of lamin-B in specific neuronal populations and muscle tissues in male flies. Ectopic expression of lamin-B in the dopaminergic neurons within the protocerebral anterior medial region of the brain improves the locomotor activity of the male flies with little impact on their stress responses and lifespan. Interestingly, age-dependent decrease in the level of lamin-B protein is independent of its mRNA expression. Instead, cellular thermal shift assay showed that lamin-B and CP190 insulator protein undergo significant change in their solubility during aging. This suggests that the increased solubility of lamin-B protein may contribute to its reduced stability and degradation during aging.
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18

Ebrahim, Shah, Joy Adamson, Salma Ayis, Andrew Beswick, and Rachael Gooberman-Hill. "Locomotor disability: Meaning, causes and effects of interventions." Journal of Health Services Research & Policy 13, no. 3_suppl (October 2008): 38–46. http://dx.doi.org/10.1258/jhsrp.2008.008013.

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Анотація:
This paper provides a synopsis of a long-term programme of MRC-funded work on locomotor disability in older people. Specifically it describes the meaning and experience of disability, examines the risk factors for disability and systematically reviews the evidence from randomized trials of complex interventions for disability. We undertook a national prospective study of a representative sample of 999 people aged 65 years or more plus in-depth interviews with a small subsample and a selected sample obtained from hospital sources. Secondary analysis of several large prospective studies was carried out and a systematic review and meta-analysis of published randomized controlled trials of the effects of complex interventions for disability. Very few participants subscribed to the constructs of longstanding illness, disability or infirmity that surveys often use. A wide range of social and psychological factors, independently of chronic diseases, were strongly associated with disability. People with greater functional reserve capacity and those with greater self-efficacy were generally less likely to suffer from catastrophic decline in ability and had better quality of life in the face of disability. In reviewing 89 trials (over 97,000 participants) of complex interventions for disability, evidence of benefits was found although no relationship with intensity of intervention was apparent. Our findings on the meaning and experience of disability suggest the need for modifications to routinely used survey questions and for different ways of understanding the need for and receipt of care among older people with disabilities. The diverse risk factors for disability suggest that novel approaches across social, psychological as well as more traditional rehabilitation and behavioural risk factor modification would be worth exploring. Complex interventions appeared to help older people to live independently and limit functional decline irrespective of age and health status.
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19

Raza, Muhammad, Othman Al-Shabanah, Tariq El-Hadiyah, Abdullah Al-Bekairi, and Shoeb Qureshi. "Antinociceptive Activity of Vigabatrin in Mice After Prolonged Treatment: Possible Development of Tolerance." Scientia Pharmaceutica 69, no. 2 (June 30, 2001): 203–10. http://dx.doi.org/10.3797/scipharm.aut-01-21.

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Анотація:
We have evaluated vigabatrin (γ-vinyi-γ-aminobutyric acid), an irreversible inhibitor of γ-aminobutyric acid (GABA)-transarninase responsible for GABA degradation, for its effects on nociceptive response, changes in spontaneous locomotor activity and body temperature in mice after a prolonged treatment regimen. The mice received vigabatrin 0.26% w/v chronically in drinking water for 7, 14 and 21 days. Changes in locomotion, body temperature and nociception were recorded after 7, 14 and 21 days respectively in different groups. Also, possible withdrawal symptoms were determined up to three days after 7, 14 or 21 days of treatment. In another experiment the animals were given acutely, 250 mg/kg of vigabatrin by oral gavage and the changes in response to the said parameters were assessed 90 min after treatment. Acute treatment increased the latency in the hot-plate reaction time and a highly significant decline in locomotion and body temperature. In contrast to the acute treatment studies, there were essentially no effects of vigabatrin on nociception, locomotor activity or body temperature either on the last day of each treatment or upon withdrawal for the next consecutive three days. We conclude that the changes in nociception, locomotion and body temperature after acute treatment with vigabatrin are due to neuromediator interactions and a possible direct effect of GABA accumulation. After prolonged treatment tolerance to the pharmacological effects of vigabatrin develop that was evident by no change in nociception, locomotion and body temperature. This may be attributed to the possible failure in the maintenance of GABA pools resulting in a reduction in enhanced GABA release mediated by vigabatrin in acute treatment. Further studies of mechanisms by which vigabatrin tolerance develops to these pharmacological responses are warranted.
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20

Wade, Francesca, Sidney Baudendistel, Amanda Stone, Jaimie Roper, Tiphanie Raffegeau, Matthew Terza, and Chris Hass. "Locomotor Adaptation Training to Prevent Mobility Disability." Biomechanics 2, no. 3 (August 4, 2022): 395–420. http://dx.doi.org/10.3390/biomechanics2030031.

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Анотація:
Mobility disability is prevalent in aging populations. While existing walking interventions improve aspects related to mobility, meaningful and sustained changes leading to preventing and reversing mobility disability have remained elusive. Split-belt treadmills can be used to train gait adaptability and may be a potential long-term rehabilitation tool for those at risk for mobility decline. As adaptability is necessary for community walking, we investigated the feasibility of a small, randomized controlled 16-week gait adaptability training program in a cohort of 38 sedentary older adults at risk for mobility disability. Individuals were randomly assigned to one of three groups: traditional treadmill training, split-belt treadmill training, or no-contact control. Both treadmill interventions included progressive training 3 days a week, focusing on increasing duration and speed of walking. Cognitive, functional, cardiovascular, and gait assessments were completed before and after the intervention. While individuals were able to complete split-belt treadmill training, only Timed Up and Go performance was significantly improved compared to traditional treadmill training. As the stimulus provided by the split-belt training was difficult to control, we did not observe a clear benefit for split-belt treadmill training over traditional treadmill training. Our findings indicate a cautionary tale about the implementation of complex training interventions.
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21

Moretti, Chiara H., Tomas A. Schiffer, Marcelo F. Montenegro, Filip J. Larsen, Vasilios Tsarouhas, Mattias Carlström, Christos Samakovlis, Eddie Weitzberg, and Jon O. Lundberg. "Dietary nitrite extends lifespan and prevents age-related locomotor decline in the fruit fly." Free Radical Biology and Medicine 160 (November 2020): 860–70. http://dx.doi.org/10.1016/j.freeradbiomed.2020.09.018.

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22

Wei, George Z., Sujata Saraswat Ohri, Nicolas K. Khattar, Adam W. Listerman, Catherine H. Doyle, Kariena R. Andres, Saravanan S. Karuppagounder, Rajiv R. Ratan, Scott R. Whittemore, and Michal Hetman. "Hypoxia-inducible factor prolyl hydroxylase domain (PHD) inhibition after contusive spinal cord injury does not improve locomotor recovery." PLOS ONE 16, no. 4 (April 5, 2021): e0249591. http://dx.doi.org/10.1371/journal.pone.0249591.

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Traumatic spinal cord injury (SCI) is a devastating neurological condition that involves both primary and secondary tissue loss. Various cytotoxic events including hypoxia, hemorrhage and blood lysis, bioenergetic failure, oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation contribute to secondary injury. The HIF prolyl hydroxylase domain (PHD/EGLN) family of proteins are iron-dependent, oxygen-sensing enzymes that regulate the stability of hypoxia inducible factor-1α (HIF-1α) and also mediate oxidative stress caused by free iron liberated from the lysis of blood. PHD inhibition improves outcome after experimental intracerebral hemorrhage (ICH) by reducing activating transcription factor 4 (ATF4)-driven neuronal death. As the ATF4-CHOP (CCAAT-enhancer-binding protein homologous protein) pathway plays a role in the pathogenesis of contusive SCI, we examined the effects of PHD inhibition in a mouse model of moderate T9 contusive SCI in which white matter damage is the primary driver of locomotor dysfunction. Pharmacological inhibition of PHDs using adaptaquin (AQ) moderately lowers acute induction of Atf4 and Chop mRNAs and prevents the acute decline of oligodendrocyte (OL) lineage mRNAs, but does not improve long-term recovery of hindlimb locomotion or increase chronic white matter sparing. Conditional genetic ablation of all three PHD isoenzymes in OLs did not affect Atf4, Chop or OL mRNAs expression levels, locomotor recovery, and white matter sparing after SCI. Hence, PHDs may not be suitable targets to improve outcomes in traumatic CNS pathologies that involve acute white matter injury.
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23

Perrochon, A., G. Kemoun, and A. Berthoz. "Can the strop test for dual task locomotor performance reveal the existence of cognitive decline?" Annals of Physical and Rehabilitation Medicine 55 (October 2012): e269. http://dx.doi.org/10.1016/j.rehab.2012.07.677.

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24

GARGANO, J., I. MARTIN, P. BHANDARI, and M. GROTEWIEL. "Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in." Experimental Gerontology 40, no. 5 (May 2005): 386–95. http://dx.doi.org/10.1016/j.exger.2005.02.005.

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25

Rizzolo, Lou, Marianne Leger, Sophie Corvaisier, Mathilde Groussard, Hervé Platel, Valentine Bouet, Pascale Schumann-Bard, and Thomas Freret. "Long-Term Music Exposure Prevents Age-Related Cognitive Deficits in Rats Independently of Hippocampal Neurogenesis." Cerebral Cortex 31, no. 1 (September 22, 2020): 620–34. http://dx.doi.org/10.1093/cercor/bhaa247.

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Abstract Cognitive decline appears across aging. While some studies report beneficial effects of musical listening and practice on cognitive aging, the underlying neurobiological mechanisms remain unknown. This study aims to determine whether chronic (6 h/day, 3 times/week) and long-lasting (4–8 months) music exposure, initiated at middle age in rats (15 months old), can influence behavioral parameters sensitive to age effects and reduce age-related spatial memory decline in rats. Spontaneous locomotor, circadian rhythmic activity, and anxiety-like behavior as well as spatial working and reference memory were assessed in 14-month-old rats and then after 4 and 8 months of music exposure (19 and 23 months old, respectively). Spatial learning and reference memory data were followed up by considering cognitive status of animals prior to music exposure (14 months old) given by K-means clustering of individual Z-score. Hippocampal cell proliferation and brain-derived neurotrophic factor (BDNF) level in the hippocampus and frontal cortex were measured. Results show that music exposure differentially rescues age-related deficits in spatial navigation tasks according to its duration without affecting spontaneous locomotor, circadian rhythmic activity, and anxiety-like behavior. Hippocampal cell proliferation as well as hippocampal and frontal cortex BDNF levels was not affected by music across aging. Cognitive improvement by music in aging rats may require distinct neurobiological mechanisms than hippocampal cell proliferation and BDNF.
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26

Dial, Kenneth P., and Brandon E. Jackson. "When hatchlings outperform adults: locomotor development in Australian brush turkeys ( Alectura lathami , Galliformes)." Proceedings of the Royal Society B: Biological Sciences 278, no. 1712 (November 3, 2010): 1610–16. http://dx.doi.org/10.1098/rspb.2010.1984.

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Анотація:
Within Galliformes, megapods (brush turkey, malleefowl, scrubfowl) exhibit unique forms of parental care and growth. Hatchlings receive no post-hatching parental care and exhibit the most exaggerated precocial development of all extant birds, hatching with fully developed, flight-capable forelimbs. Rather than flying up to safety, young birds preferentially employ wing-assisted incline running. Newly hatched Australian brush turkeys ( Alectura lathami ) are extraordinarily proficient at negotiating all textured inclined surfaces and can flap-walk up inclines exceeding the vertical. Yet, as brush turkeys grow, their forelimb-dependent locomotor performance declines. In an attempt to elucidate how hatchlings perform so well, we analysed hindlimb forces and forelimb kinematics. We measured ground reaction forces (GRFs) for animals spanning the entire growth range (110–2000 g) as they ascended a variably positioned inclined ramp that housed a forceplate. These data are compared with a similar dataset for a chukar partridge ( Alectoris chukar ) that exhibit a growth strategy typical of most other Galliformes and that demonstrate improved incline performance with increasing age. The brush turkeys' ontogenetic decline in incline running performance is accompanied by loss of traction at steep angles, reduced GRFs and increased wing-loading. We hypothesize that Australian brush turkeys, in contrast to other Galliformes, develop from forelimb-dominated young that exploit a variable terrain (e.g. mound nests, boulders, embankments, cliffs, bushes and trees) into hindlimb-dominated adults dependent on size and running speed to avoid predation.
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27

Hastings, M. H., A. P. Walker, and J. Herbert. "Effect of asymmetrical reductions of photoperiod on pineal melatonin, locomotor activity and gonadal condition of male Syrian hamsters." Journal of Endocrinology 114, no. 2 (August 1987): 221–29. http://dx.doi.org/10.1677/joe.0.1140221.

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ABSTRACT This study investigated the relationship of two overt circadian rhythms, locomotor activity and melatonin synthesis in the pineal gland, by comparing their responses to asymmetrical reductions in photoperiod. Transfer of male Syrian hamsters from long to short daylengths led to an increase in the duration of both locomotor activity and the period of melatonin synthesis. Over the course of re-entrainment, the two rhythms were held in a stable phase relationship, and the direction of the switch did not influence the rate of decompression or the final phase relationships established after 8 weeks in short daylengths. Decompression of the activity rhythm was not influenced by pinealectomy. Exposure to short photoperiods caused gonadal regression and a consequent decline in serum testosterone levels from 10 to <1 nmol/l. The direction of the photoperiodic switch did not affect the time-course of gonadal regression. These data demonstrate the important influence of photoperiod upon the duration of the nocturnal peak of melatonin production by the pineal and also demonstrate that this effect is one example of a more widespread response of the circadian system. A qualitatively similar signal controls both locomotor activity and melatonin synthesis, although the neural basis of this common mechanism is unclear. J. Endocr. (1987) 114, 221–229
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28

Kent-Braun, Jane A., and Alexander V. Ng. "Skeletal muscle oxidative capacity in young and older women and men." Journal of Applied Physiology 89, no. 3 (September 1, 2000): 1072–78. http://dx.doi.org/10.1152/jappl.2000.89.3.1072.

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It has been suggested that a decline in skeletal muscle oxidative capacity is a general consequence of aging in humans. However, previous studies have not always controlled for the effects of varying levels of physical activity on muscle oxidative capacity. To test the hypothesis that, when matched for comparable habitual physical activity levels, there would be no age-related decline in the oxidative capacity of a locomotor muscle, the postexercise recovery time of phosphocreatine was compared in the tibialis anterior muscle of young [ n = 19; 33.8 ± 4.8 (SD) yr] and older [ n = 18; 75.5 ± 4.5 yr] healthy women and men of similar, relatively low, activity levels. The intramuscular metabolic measurements were accomplished by using phosphorus magnetic resonance spectroscopy. The results indicate that there was no age effect on the postexercise recovery time of phosphocreatine recovery, thus supporting the stated hypothesis. These data suggest that there is no requisite decline in skeletal muscle oxidative capacity with aging in humans, at least through the seventh decade.
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29

Kraimi, N., G. De Palma, J. Lu, D. Bowdish, E. Verdu, E. Sibille, T. Prevot, S. M. Collins, and P. Bercik. "A14 THE INTESTINAL MICROBIOTA CONTRIBUTES TO AGE-RELATED MEMORY DECLINE." Journal of the Canadian Association of Gastroenterology 5, Supplement_1 (February 21, 2022): 17–18. http://dx.doi.org/10.1093/jcag/gwab049.013.

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Abstract Background Age-related deterioration of cognitive function and memory capacity occur in both humans and rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., 2019, Mol Neuropsychiatry 5, 84–97). Microbiota-to-brain signaling is now well established in mice and humans, but the extent to which it influences age-associated memory decline is unknown. Aims Our study examines whether the intestinal microbiota contributes to age-associated changes in brain function. We address the specific hypothesis that age-associated cognitive decline is attenuated in the absence of the intestinal microbiota. Methods We assessed anxiety-like and depressive-like behavior, locomotor activity and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice of the same age. Anxiety-like behavior, locomotor activity and depressive-like behavior were measured using the light-dark preference, open-field, and tail suspension tests. We also used the Y-maze test based on a spontaneous alternation task to assess cognition, with the alternation rate as a proxy of spatial working memory. The age-associated inflammation was assessed with IL-6 cytokine plasma concentrations measured by ELISA. Results Anxiety-like behavior and depressive-like behavior did not change with the age regardless of the microbial status. However, old SPF mice traveled less distance (866.8 cm) than young SPF mice (1375 cm, p &lt; 0.01) in the open-field. Similarly, old GF mice also traveled less distance (458.9 cm) than young GF mice (875.7 cm, p &lt; 0.0001). In contrast to old SPF mice, old GF mice did not show memory impairment in the spatial memory task. Indeed, old SPF mice displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.9%, p &lt; 0.05) while both old and young GF mice had an identical alternation rate of 73.3% ( p &gt; 0.05). In addition, IL-6 plasma levels revealed that old GF mice did not show signs of age-associated inflammation that was evident in old SPF mice (3.68 vs. 13.93 pg/ml, p &lt; 0.05). Conclusions We conclude that the absence of age-related memory deficit in old germ-free mice is consistent with a role for the microbiota in age-related cognitive decline, likely mediated via the immune system, as suggested by the absence of age-associated inflammation in germ-free mice. We propose that novel microbiota-targeted therapeutic strategies may prevent or delay the cognitive decline of aging. Funding Agencies CIHRBalsam Family Foundation
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30

Vallejos, Maximiliano J., Abdunaser Eadaim, Eu-Teum Hahm, and Susan Tsunoda. "Age-related changes in Kv4/Shal and Kv1/Shaker expression in Drosophila and a role for reactive oxygen species." PLOS ONE 16, no. 12 (December 21, 2021): e0261087. http://dx.doi.org/10.1371/journal.pone.0261087.

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Age-related changes in ion channel expression are likely to affect neuronal signaling. Here, we examine how age affects Kv4/Shal and Kv1/Shaker K+ channel protein levels in Drosophila. We show that Kv4/Shal protein levels decline sharply from 3 days to 10 days, then more gradually from 10 to 40 days after eclosion. In contrast, Kv1/Shaker protein exhibits a transient increase at 10 days that then stabilizes and eventually declines at 40 days. We present data that begin to show a relationship between reactive oxygen species (ROS), Kv4/Shal, and locomotor performance. We show that Kv4/Shal levels are negatively affected by ROS, and that over-expression of Catalase or RNAi knock-down of the ROS-generating enzyme, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase (NOX), can attenuate the loss of Kv4/Shal protein. Finally, we compare levels of Kv4.2 and Kv4.3 in the hippocampus, olfactory bulb, cerebellum, and motor cortex of mice aged 6 weeks and 1 year. While there was no global decline in Kv4.2/4.3 that parallels what we report in Drosophila, we did find that Kv4.2/4.3 are differentially affected in various brain regions; this survey of changes may help inform mammalian studies that examine neuronal function with age.
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31

Banerjee, Surya Jyoti, Adina Schonbrun, Sogol Eizadshenass, Shimshon Benji, Yaakov Tzvi Cantor, Liam Eliach, Matthew Lubin, et al. "iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster." PLOS ONE 16, no. 9 (September 10, 2021): e0256738. http://dx.doi.org/10.1371/journal.pone.0256738.

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Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN.
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32

Sosniyenko, Serhiy, Daniela Parkanová, Helena Illnerová, Martin Sládek, and Alena Sumová. "Different mechanisms of adjustment to a change of the photoperiod in the suprachiasmatic and liver circadian clocks." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 298, no. 4 (April 2010): R959—R971. http://dx.doi.org/10.1152/ajpregu.00561.2009.

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Changes in photoperiod modulate the circadian system, affecting the function of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The aim of the present study was to elucidate the dynamics of adjustment to a change of a long photoperiod with 18 h of light to a short photoperiod with 6 h of light of clock gene expression rhythms in the mouse SCN and in the peripheral clock in the liver, as well as of the locomotor activity rhythm. Three, five, and thirteen days after the photoperiod change, daily profiles of Per1, Per2, and Rev-erbα expression in the rostral, middle, and caudal parts of the SCN and of Per2 and Rev-erbα in the liver were determined by in situ hybridization and real-time RT-PCR, respectively. The clock gene expression rhythms in the different SCN regions, desynchronized under the long photoperiod, attained synchrony gradually following the transition from long to short days, mostly via advancing the expression decline. The photoperiodic modulation of the SCN was due not only to the degree of synchrony among the SCN regions but also to different waveforms of the rhythms in the individual SCN parts. The locomotor activity rhythm adjusted gradually to short days by advancing the activity onset, and the liver rhythms adjusted by advancing the Rev-erbα expression rise and Per2 decline. These data indicate different mechanisms of adjustment to a change of the photoperiod in the central SCN clock and the peripheral liver clock.
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33

Lylyk, M., O. Sorochynska, O. Maniukh, and M. Bayliak. "Age-related physiological and biochemical changes in Drosophila grown on alpha-ketoglutarate." Bulletin of Taras Shevchenko National University of Kyiv. Series: Problems of Physiological Functions Regulation 22, no. 1 (2017): 25–31. http://dx.doi.org/10.17721/2616_6410.2017.22.25-31.

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In the work, certain metabolic parameters and parameters of functional senescence were studied in the fruit fly D. melanogaster w1118 males fed with alpha-ketoglutarate (AKG). Dietary increased levels of amino acids and protein in 2-day-old males and levels of triacylglycerols in 24-day-old males with no effect on antioxidant system of males of both age groups. In addition, AKG-supplemented food increased resistance to heat stress but not to oxidants in both age groups and prevented the decline in locomotor activity in middle-aged males.
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34

Fu, Amy K. Y., Kwok-Wang Hung, Michael Y. F. Yuen, Xiaopu Zhou, Deejay S. Y. Mak, Ivy C. W. Chan, Tom H. Cheung, et al. "IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline." Proceedings of the National Academy of Sciences 113, no. 19 (April 18, 2016): E2705—E2713. http://dx.doi.org/10.1073/pnas.1604032113.

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Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.
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35

Cannon, Daniel T., Ana Claudia Coelho, Robert Cao, Andrew Cheng, Janos Porszasz, Richard Casaburi, and Harry B. Rossiter. "Skeletal muscle power and fatigue at the tolerable limit of ramp-incremental exercise in COPD." Journal of Applied Physiology 121, no. 6 (December 1, 2016): 1365–73. http://dx.doi.org/10.1152/japplphysiol.00660.2016.

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Muscle fatigue (a reduced power for a given activation) is common following exercise in chronic obstructive pulmonary disease (COPD). Whether muscle fatigue, and reduced maximal voluntary locomotor power, are sufficient to limit whole body exercise in COPD is unknown. We hypothesized in COPD: 1) exercise is terminated with a locomotor muscle power reserve; 2) reduction in maximal locomotor power is related to ventilatory limitation; and 3) muscle fatigue at intolerance is less than age-matched controls. We used a rapid switch from hyperbolic to isokinetic cycling to measure the decline in peak isokinetic power at the limit of incremental exercise (“performance fatigue”) in 13 COPD patients (FEV1 49 ± 17%pred) and 12 controls. By establishing the baseline relationship between muscle activity and isokinetic power, we apportioned performance fatigue into the reduction in muscle activation and muscle fatigue. Peak isokinetic power at intolerance was ~130% of peak incremental power in controls (274 ± 73 vs. 212 ± 84 W, P < 0.05), but ~260% in COPD patients (187 ± 141 vs. 72 ± 34 W, P < 0.05), greater than controls ( P < 0.05). Muscle fatigue as a fraction of baseline peak isokinetic power was not different in COPD patients vs. controls (0.11 ± 0.20 vs. 0.19 ± 0.11). Baseline to intolerance, the median frequency of maximal isokinetic muscle activity, was unchanged in COPD patients but reduced in controls (+4.3 ± 11.6 vs. −5.5 ± 7.6%, P < 0.05). Performance fatigue as a fraction of peak incremental power was greater in COPD vs. controls and related to resting (FEV1/FVC) and peak exercise (V̇E/maximal voluntary ventilation) pulmonary function ( r2 = 0.47 and 0.55, P < 0.05). COPD patients are more fatigable than controls, but this fatigue is insufficient to constrain locomotor power and define exercise intolerance.
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36

Wiklund, Andreas, Sylvie Granon, Isabelle Cloëz-Tayarani, Philippe Faure, Anne-Marie le Sourd, Eva Sundman, Jean-Pierre Changeux та Lars I. Eriksson. "Sevoflurane Anesthesia Alters Exploratory and Anxiety-like Behavior in Mice Lacking the β2Nicotinic Acetylcholine Receptor Subunit". Anesthesiology 109, № 5 (1 листопада 2008): 790–98. http://dx.doi.org/10.1097/aln.0b013e31818a379a.

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Background Preexisting cognitive impairment and advanced age are factors that increase the risk of developing postoperative cognitive dysfunction. Because anesthetic agents interfere with cholinergic transmission and as impairment of cholinergic function is associated with cognitive decline, the authors studied how the volatile anesthetic sevoflurane affects exploratory and anxiety-like behavior in young and aged animals with a genetically modified cholinergic system. Methods Young and aged wild-type and mutant mice lacking the beta2 subunit of the nicotinic cholinergic receptor (beta2KO) were anesthetized for 2 h with 2.6% sevoflurane in oxygen and compared with nonanesthetized controls. Locomotor activity and organization of movement in the open field model were assessed before and 24 h after anesthesia. Locomotor activity and anxiety-like behavior in the elevated plus maze were assessed 24 h after anesthesia. High- and low-affinity nicotinic receptor and cholinergic uptake site densities were evaluated in the hippocampus, amygdala, and forebrain regions using receptor autoradiography. Results Sevoflurane anesthesia significantly reduced locomotor activity, altered temporospatial organization of trajectories, and increased anxiety-like behavior in young beta2KO mice, whereas no such changes were observed in young wild-type mice. Aged wild-type and beta2KO mice displayed reactions that were similar, but not identical, to the reactions of young mice to sevoflurane anesthesia. However, behavioral changes were not associated with differences in nicotinic receptor or cholinergic uptake site densities. Conclusion In conclusion, sevoflurane anesthesia altered exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.
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37

Chu, Winston T., Jesse C. DeSimone, Cara J. Riffe, Han Liu, Paramita Chakrabarty, Benoit I. Giasson, Vinata Vedam-Mai та David E. Vaillancourt. "α-Synuclein Induces Progressive Changes in Brain Microstructure and Sensory-Evoked Brain Function That Precedes Locomotor Decline". Journal of Neuroscience 40, № 34 (15 липня 2020): 6649–59. http://dx.doi.org/10.1523/jneurosci.0189-20.2020.

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38

Chamberlain Jr., John A. "Jet propulsion of Nautilus: a surviving example of early Paleozoic cephalopod locomotor design." Canadian Journal of Zoology 68, no. 4 (April 1, 1990): 806–14. http://dx.doi.org/10.1139/z90-116.

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Like its coleoid relatives, Nautilus swims by jet propulsion. However, in the structure and functioning of its motor, Nautilus differs markedly from its contemporaries. Compared with that of squids, Nautilus locomotion is based on small propellant volume, low mantle cavity pressure, low propellant velocity, and small propulsive muscle mass. Propulsive performance of Nautilus is consequently unspectacular, with as little as one-eighth the thrust and one-tenth the burst speed observed in squids of equivalent size. Nautilus survives as a result of its slow-moving, vertically mobile, foraging life-style limited to habitats where competition with fast-moving, agile swimmers is minimal. Fossil cephalopods faced similar design constraints, which may have contributed to their decline, but nonbiologic factors such as sea level fluctuations may also have been important in directing the course of cephalopod evolution.
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39

Feng, Xiaomei, Vincent Degos, Lauren G. Koch, Steven L. Britton, Yinggang Zhu, Susana Vacas, Niccolò Terrando, Jeffrey Nelson, Xiao Su, and Mervyn Maze. "Surgery Results in Exaggerated and Persistent Cognitive Decline in a Rat Model of the Metabolic Syndrome." Anesthesiology 118, no. 5 (May 1, 2013): 1098–105. http://dx.doi.org/10.1097/aln.0b013e318286d0c9.

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Abstract Background: Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. Methods: In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. Results: On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Conclusion: Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.
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40

Warner, Amy, Preeti H. Jethwa, Catherine A. Wyse, Helen I'Anson, John M. Brameld, and Francis J. P. Ebling. "Effects of photoperiod on daily locomotor activity, energy expenditure, and feeding behavior in a seasonal mammal." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 298, no. 5 (May 2010): R1409—R1416. http://dx.doi.org/10.1152/ajpregu.00279.2009.

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The objective of this study was to determine whether the previously observed effects of photoperiod on body weight in Siberian hamsters were due to changes in the daily patterns of locomotor activity, energy expenditure, and/or feeding behavior. Adult males were monitored through a seasonal cycle using an automated comprehensive laboratory animal monitoring system (CLAMS). Exposure to a short-day photoperiod (SD; 8:16-h light-dark cycle) induced a significant decline in body weight, and oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and heat production all decreased reaching a nadir by 16 wk of SD. Clear daily rhythms in locomotor activity, V̇o2, and V̇co2 were observed at the start of the study, but these all progressively diminished after prolonged exposure to SD. Rhythms in feeding behavior were also detected initially, reflecting an increase in meal frequency but not duration during the dark phase. This rhythm was lost by 8 wk of SD exposure such that food intake was relatively constant across dark and light phases. After 18 wk in SD, hamsters were transferred to a long-day photoperiod (LD; 16:8-h light-dark cycle), which induced significant weight gain. This was associated with an increase in energy intake within 2 wk, while V̇o2, V̇co2, and heat production all increased back to basal levels. Rhythmicity was reestablished within 4 wk of reexposure to long days. These results demonstrate that photoperiod impacts on body weight via complex changes in locomotor activity, energy expenditure, and feeding behavior, with a striking loss of daily rhythms during SD exposure.
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41

Gelegen, Cigdem, David A. Collier, Iain C. Campbell, Hugo Oppelaar, and Martien J. H. Kas. "Behavioral, physiological, and molecular differences in response to dietary restriction in three inbred mouse strains." American Journal of Physiology-Endocrinology and Metabolism 291, no. 3 (September 2006): E574—E581. http://dx.doi.org/10.1152/ajpendo.00068.2006.

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Food restriction paradigms are widely used in animal studies to investigate systems involved in energy regulation. We have observed behavioral, physiological, and molecular differences in response to food restriction in three inbred mouse strains, C57BL/6J, A/J, and DBA/2J. These are the progenitors of chromosome substitution and recombinant inbred mouse strains used for mapping complex traits. DBA/2J and A/J mice increased their locomotor activity during food restriction, and both displayed a decrease in body temperature, but the decrease was significantly larger in DBA/2J compared with A/J mice. C57BL/6J mice did not increase their locomotor activity and displayed a large decrease in their body temperature. The large decline in body temperature during food restriction in DBA/2J and C57BL/6J strains was associated with a robust reduction in plasma leptin levels. DBA/2J mice showed a marked decrease in white and brown adipose tissue masses and an upregulation of the antithermogenic hypothalamic neuropeptide Y Y1 receptor. In contrast, A/J mice showed a reduction in body temperature to a lesser extent that may be explained by downregulation of the thermogenic melanocortin 3 receptor and by behavioral thermoregulation as a consequence of their increased locomotor activity. These data indicate that genetic background is an important parameter in controlling an animal's adaptation strategy in response to food restriction. Therefore, mouse genetic mapping populations based on these progenitor lines are highly valuable for investigating mechanisms underlying strain-dependent differences in behavioral physiology that are seen during reduced food availability.
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42

Scisciola, Lucia, Rosaria Anna Fontanella, Surina, Vittoria Cataldo, Giuseppe Paolisso, and Michelangela Barbieri. "Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk." Life 11, no. 2 (February 23, 2021): 173. http://dx.doi.org/10.3390/life11020173.

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Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or more cognitive domains as language, memory, reasoning, social cognition, planning, making decisions, and solving problems. Although the exact mechanism relating to sarcopenia and cognitive function has not yet been defined, several studies have shown that skeletal muscle produces and secrete molecules, called myokines, that regulate brain functions, including mood, learning, locomotor activity, and neuronal injury protection, showing the existence of muscle-brain cross-talk. Moreover, studies conducted on physical exercise supported the existence of muscle-brain cross-talk, showing how physical activity, changing myokines' circulating levels, exerts beneficial effects on the brain. The review mainly focuses on describing the role of myokines on brain function and their involvement in cognitive impairment in sarcopenia.
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43

Francisco, Michael A., Joshua F. Lee, Zachary Barrett-O’Keefe, H. Jonathan Groot, Stephen M. Ratchford, Kanokwan Bunsawat, Jeremy K. Alpenglow, et al. "Locomotor Muscle Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction." Hypertension 78, no. 6 (December 2021): 1750–59. http://dx.doi.org/10.1161/hypertensionaha.121.17875.

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While there is emerging evidence of peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction (HFpEF) that may be related to systemic inflammation and redox imbalance, disease-related changes in locomotor muscle microvascular responsiveness have not been determined. This study combined passive leg movement and biomarker assessments of inflammation and oxidative damage to determine the magnitude and mechanisms of lower limb microvascular function in patients with HFpEF (71±1 years; n=44) compared with healthy, similarly aged controls (68±2 years; n=39). Leg blood flow, heart rate, mean arterial pressure, and stroke volume were assessed, and plasma biomarkers of inflammation and oxidative damage were also determined. A significantly attenuated passive leg movement–induced peak change in leg blood flow (263±25 versus 371±31 mL/min, HFpEF versus control) and leg vascular conductance (2.99±0.32 versus 3.88±0.34 mL/min per mm Hg, HFpEF versus control) was observed in patients compared with controls. Similarly, the total hyperemic response to passive leg movement, expressed as leg blood flow AUC and leg vascular conductance AUC , was ≈40% less in patients with HFpEF versus control. Significantly greater C-reactive protein, IL-6 (interleukin-6), and malondialdehyde were observed in patients with HFpEF but were not correlated with passive leg movement responses. These data provide new evidence of a decline in lower limb microvascular function within a milieu of vascular inflammation that may contribute to locomotor muscle dysfunction in patients with HFpEF.
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44

Felippe, Leandro Camati, Guilherme Assunção Ferreira, Sara Kely Learsi, Daniel Boari, Romulo Bertuzzi, and Adriano Eduardo Lima-Silva. "Caffeine increases both total work performed above critical power and peripheral fatigue during a 4-km cycling time trial." Journal of Applied Physiology 124, no. 6 (June 1, 2018): 1491–501. http://dx.doi.org/10.1152/japplphysiol.00930.2017.

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The link between total work performed above critical power (CP) and peripheral muscle fatigue during self-paced exercise is unknown. We investigated the influence of caffeine on the total work done above CP during a 4-km cycling time trial (TT) and the subsequent consequence on the development of central and peripheral fatigue. Nine cyclists performed three constant-load exercise trials to determine CP and two 4-km TTs ~75 min after oral caffeine (5 mg/kg) or cellulose (placebo) ingestion. Neuromuscular functions were assessed before and 50 min after supplementation and 1 min after TT. Oral supplementation alone had no effect on neuromuscular function ( P > 0.05). Compared with placebo, caffeine increased mean power output (~4%, P = 0.01) and muscle recruitment (as inferred by EMG, ~17%, P = 0.01) and reduced the time to complete the TT (~2%, P = 0.01). Work performed above CP during the caffeine trial (16.7 ± 2.1 kJ) was significantly higher than during the placebo (14.7 ± 2.1 kJ, P = 0.01). End-exercise decline in quadriceps twitch force (pre- to postexercise decrease in twitch force at 1 and 10 Hz) was more pronounced after caffeine compared with placebo (121 ± 13 and 137 ± 14 N vs. 146 ± 13 and 156 ± 11 N; P < 0.05). There was no effect of caffeine on central fatigue. In conclusion, caffeine increases muscle recruitment, which enables greater work performed above CP and higher end-exercise peripheral locomotor muscle fatigue. NEW & NOTEWORTHY The link between total work done above critical power and peripheral fatigue during a self-paced, high-intensity exercise is unclear. This study revealed that caffeine ingestion increases muscle recruitment, which enables greater work done above critical power and a greater degree of end-exercise decline in quadriceps twitch force during a 4-km cycling time trial. These findings suggest that caffeine increases performance at the expense of greater locomotor muscle fatigue.
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45

Deng, Jing, Xin-Xin Guan, Ying-Bao Zhu, Hai-Tao Deng, Guang-Xu Li, Yi-Chen Guo, Peng Jin, Ran-Hui Duan, and Wen Huang. "Reducing the Excess Activin Signaling Rescues Muscle Degeneration in Myotonic Dystrophy Type 2 Drosophila Model." Journal of Personalized Medicine 12, no. 3 (March 2, 2022): 385. http://dx.doi.org/10.3390/jpm12030385.

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Expanded non-coding RNA repeats of CCUG are the underlying genetic causes for myotonic dystrophy type 2 (DM2). There is an urgent need for effective medications and potential drug targets that may alleviate the progression of the disease. In this study, 3140 small-molecule drugs from FDA-approved libraries were screened through lethality and locomotion phenotypes using a DM2 Drosophila model expressing 720 CCTG repeats in the muscle. We identified ten effective drugs that improved survival and locomotor activity of DM2 flies, including four that share the same predicted targets in the TGF-β pathway. The pathway comprises two major branches, the Activin and BMP pathways, which play critical and complex roles in skeletal development, maintenance of homeostasis, and regeneration. The Drosophila model recapitulates pathological features of muscle degeneration in DM2, displaying shortened lifespan, a decline in climbing ability, and progressive muscle degeneration. Increased levels of p-smad3 in response to activin signaling were observed in DM2 flies. Decreased levels of activin signaling using additional specific inhibitors or genetic method ameliorated climbing defects, crushed thoraxes, structure, and organization of muscle fibers. Our results demonstrate that a decrease in activin signaling is sufficient to rescue muscle degeneration and is, therefore, a potential therapeutic target for DM2.
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46

So, Simon W., Kendra M. Fleming, Cayla M. Duffy, Joshua P. Nixon, David A. Bernlohr, and Tammy A. Butterick. "Microglial FABP4-UCP2 Axis Modulates Neuroinflammation and Cognitive Decline in Obese Mice." International Journal of Molecular Sciences 23, no. 8 (April 14, 2022): 4354. http://dx.doi.org/10.3390/ijms23084354.

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The microglial fatty-acid-binding protein 4-uncoupling protein 2 (FABP4-UCP2) axis is a key regulator of neuroinflammation in high-fat-diet (HFD)-fed animals, indicating a role for FABP4 in brain immune response. We hypothesized that the FABP4-UCP2 axis is involved in regulating diet-induced cognitive decline. We tested cognitive function in mice lacking microglial FABP4 (AKO mice). Fifteen-week-old male AKO and wild-type (WT) mice were maintained on 60% HFD or normal chow (NC) for 12 weeks. Body composition was measured using EchoMRI. Locomotor activity, working memory, and spatial memory were assessed using behavioral tests (open field, T-maze, and Barnes maze, respectively). Hippocampal microgliosis was assessed via immunohistochemical staining. An inflammatory cytokine panel was assayed using hippocampal tissue. Real-time RT-PCR was performed to measure microglial UCP2 mRNA expression. Our data support that loss of FABP4 prevents cognitive decline in vivo. HFD-fed WT mice exhibited impaired long- and short-term memory, in contrast with HFD-fed AKO mice. HFD-fed WT mice had an increase in hippocampal inflammatory cytokine expression (IFNγ, IL-1β, IL-5, IL-6, KC/GRO(CXCL1), IL-10, and TNFα) and microgliosis, and decreased microglial UCP2 expression. HFD-fed AKO mice had decreased hippocampal inflammatory cytokine expression and microgliosis and increased microglial UCP2 expression compared to HFD-fed WT mice. Collectively, our work supports the idea that the FABP4-UCP2 axis represents a potential therapeutic target in preventing diet-induced cognitive decline.
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47

Foulkes, Jonathan D., Zoe Knowles, Stuart J. Fairclough, Gareth Stratton, Mareesa V. O’Dwyer, and Lawrence Foweather. "Is Foundational Movement Skill Competency Important for Keeping Children Physically Active and at a Healthy Weight?" International Journal of Environmental Research and Public Health 19, no. 1 (December 23, 2021): 105. http://dx.doi.org/10.3390/ijerph19010105.

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This longitudinal study examines the associations between foundational movement skills (FMS) competency, moderate-to-vigorous physical activity (MVPA) and weight status among children (n = 75) attending preschools in deprived areas from early to late childhood. Twelve FMS were assessed using the Children’s Activity and Movement in Preschool Motor Skills Protocol and video analysis. Physical activity was measured via hip-mounted accelerometry. Data was collected over a five-year period, with Baseline Follow Up data collected between 2010 and 2015. There was an overall pattern of increase for total, object-control and locomotor scores between Baseline and Follow-Up. Conversely, there was an overall pattern of decline for MVPA among participants. There was a positive significant (p < 0.05) association between total and locomotor scores and MVPA at Baseline. However, these associations weakened over time and no significant associations were found at Follow-Up. Baseline competency failed to predict Follow-Up MVPA or weight status. Likewise, Baseline MVPA was not found to be a predictor of Follow-Up FMS competency. Further longitudinal research is required to explore these associations among children from highly deprived areas. Future interventions may require a more holistic approach to improving FMS competency and increasing PA in order to account for the number of variables that can affect these outcomes.
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48

Sinnamon, H. M. "Decline in hippocampal theta activity during cessation of locomotor approach sequences: Amplitude leads frequency and relates to instrumental behavior." Neuroscience 140, no. 3 (January 2006): 779–90. http://dx.doi.org/10.1016/j.neuroscience.2006.02.058.

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49

Johannsen, Leif, Erik Friedgen, Denise Nadine Stephan, Joao Batista, Doreen Schulze, Thea Laurentius, Iring Koch, and Leo Cornelius Bollheimer. "Keeping in step with the young: Chronometric and kinematic data show intact procedural locomotor sequence learning in older adults." PLOS ONE 17, no. 5 (May 3, 2022): e0266733. http://dx.doi.org/10.1371/journal.pone.0266733.

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Sequence learning in serial reaction time tasks (SRTT) is an established, lab-based experimental paradigm to study acquisition and transfer of skill based on the detection of predictable stimulus and motor response sequences. Sequence learning has been mainly studied in key presses using visual target stimuli and is demonstrated by better performance in predictable sequences than in random sequences. In this study, we investigated sequence learning in the context of more complex locomotor responses. To this end, we developed a novel goal-directed stepping SRTT with auditory target stimuli in order to subsequently assess the effect of aging on sequence learning in this task, expecting that age-related performance reductions in postural control might disturb the acquisition of the sequence. We used pressure-sensitive floor mats to characterise performance across ten blocks of trials. In Experiment 1, 22 young adults demonstrated successful acquisition of the sequence in terms of the time to step on the target mat and percent error and thus validated our new paradigm. In Experiment 2, in order to contrast performance improvements in the stepping SRTT between 27 young and 22 old adults, motion capture of the feet was combined with the floor mat system to delineate individual movement phases during stepping onto a target mat. The latencies of several postural events as well as other movement parameters of a step were assessed. We observed significant learning effects in the latency of step initiation, the time to step on the target mat, and motion parameters such as stepping amplitude and peak stepping velocity, as well as in percent error. The data showed general age-related slowing but no significant performance differences in procedural locomotor sequence learning between young and old adults. The older adults also had comparable conscious representations of the sequence of stimuli as the young adults. We conclude that sequence learning occurred in this locomotor learning task that is much more complex than typical finger-tapping sequence learning tasks, and that healthy older adults showed similar learning effects compared to young adults, suggesting intact locomotor sequence learning capabilities despite general slowing and normal age-related decline in sensorimotor function.
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50

Malviya, Meghana, Neetesh Kumar Jain, Rohit Singhal, and Narendra Silawat. "Evaluation of Anti-Parkinson Activity of Aqueous Extract of Barleria prionitis." International Journal of Medical Sciences and Pharma Research 8, no. 2 (June 15, 2022): 39–34. http://dx.doi.org/10.22270/ijmspr.v8i2.34.

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AIM- The aim of the preset investigation is Evaluation of Anti-Parkinson Activity of Aqueous Extract of Barleria prionitis. MATERIAL & METHODS- The whole plant of Barleria prionitiswere collected from the surrounding areas of Erode district, Tamilnadu, India during the month of December. Coarsely powdered whole plant of Barleria prionitis were extracted with water for 48 hours at room temperature. After extraction the extracts were evaporated by using rotary evaporator and dried at room temperature. The obtained crude extracts were weighed and stored at 4ᵒC for the further analysis. Male Swiss albino mice 3 month of age, and 25-30 g body weight were offered. All the rats were kept at room temperature and allowed to acclimate in standard conditions less than 12 hr light/ 12 hr dark cycle in the animal house. The MPTP was purchased from sigma chemicals, Mumbai, India and was stored according to the manufacturer label (370C) to prevent its decomposition. The length of time (duration) the animal stay on the rod without falling, gives a measure of their coordination, balance, physical condition and motor-planning. RESULTS- The grip strength of treated rats were found to be increased in the rats as compared to untreated rats. Similarly, Locomotor activity were also significantly increased in the rats treated in rats as compared to untreated rats. DISCUSSION- From the results the Actophotometer readings (locomotor activity) of animals of vehicle-treated control group (Group I) was found to be 386.33±1.56 and 396±1.15 counts/5 min for all 7 days of treatment. MPTP treatment to animals of Group II showed a significant reduction in locomotor activity every week. The actophotometer readings decreased to 186±2.30 counts/ 5 min. on the 7th day, went down to 145.33±0.23 counts/5 min. Thus, there was a significant decline in the locomotor activity of rotenone treated control animals (Group III) when compared to vehicle-treated control group (Group I). CONCLUSION- From the present study, it can be considered that the aqueous extract of Barleria prionitis exhibited significant anti-parkinsonism activity in MPTP model in mouse and rats respectively. KEYWORDS- Anti-Parkinson Activity, Aqueous Extract, Barleria prionitis, Parkinson Disease, Muscular rigidity, Bradykinesia
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