Dissertations / Theses on the topic 'Choroba Parkinsona'

In this thesis I used of a range of genetic methodologies and strategies to unravel the genetic bases of Parkinson disease (PD), myoclonus-dystonia (M-D), and chorea. First, I detail the work I performed in PD, including (1) the screening of GBA in a cohort of early-onset PD cases, which led to the identification of the allele E326K (p.Glu365Lys) as the single most frequent, clinically relevant, risk variant for PD; (2) a detailed genetic analysis in a large cohort of PD cases who underwent deep-brain stimulation treatment and a longitudinal comparison of the phenotypic features of carriers of mutations in different genes; (3) the observation that rare GCH1 coding variants, known to be responsible for the childhood-onset disorder DOPA-responsive dystonia, are a novel risk factor for PD. Then, I describe the work I performed to identify novel causes of M-D, including (1) the discovery of the missense p.Arg145His mutation in KCTD17 as a novel cause of autosomal dominant M-D; (2) the identification of tyrosine hydroxylase deficiency as a novel treatable cause of recessive M-D; and (3) the conclusive disproof of the pathogenic role of the p.Arg1389His variant in CACNA1B as a cause of M-D. Finally, I detail my work in the field of choreic syndromes, including (1) the genetic screening of NKX2-1 in the Queen Square cohort of benign hereditary chorea (BHC) cases; (2) the identification of ADCY5 mutations, the gene thought to be responsible for the condition familial dyskinesias with facial myokymia, as an important cause of BHC; and (3) the identification of de novo mutations in PDE10A as a novel genetic cause of chorea. These findings are discussed in light of the recent literature. Following my analysis, I suggest future directions for the identification of novel genetic causes of movement disorders, in light of my recent findings and ongoing research.

This work deals with the diagnosis of Parkinson's disease by analyzing the speech signal. At the beginning of this work there is described speech signal production. The following is a description of the speech signal analysis, its preparation and subsequent feature extraction. Next there is described Parkinson's disease and change of the speech signal by this disability. The following describes the symptoms, which are used for the diagnosis of Parkinson's disease (FCR, VSA, VOT, etc.). Another part of the work deals with the selection and reduction symptoms using the learning algorithms (SVM, ANN, k-NN) and their subsequent evaluation. In the last part of the thesis is described a program to count symptoms. Further is described selection and the end evaluated all the result.

Thesis named Calculation of advanced diffusion parameters in brain grey matter from DKI MRI images deals with processing of diffusion-weighted images from DKI. The thesis contains review of literature on principle of diffusion, influence of diffusion on MRI, calculation of DTI and DKI parameters and clinical application of diffusion-weighted maps with focus on grey matter. The thesis focuses on software tools for processing and pre-processing DTI and DKI. The practical part consisted of two sections. Two different softwares were used to calculate maps of diffusion parameters. Diffusion parameters from anatomical structure sunstantia nigra were compared between group of healthy controls and patients with Parkinson’s disease. This comparison did not show any statisticaly significant difference. In the second step, a script for creating diffusion maps in software Diffusinal Kurtosis Estimator was made.

Hĺbková mozgová stimulácia (DBS) predstavuje účinnú liečbu pre pacientov s Parkinsonovou chorobou (PD) alebo farmakorezistentnou epilepsiou. Avšak mechanizmy, ktorými znižuje počet záchvatov a zlepšuje pohyb, zostávajú ešte do značnej miery neznáme. Pre lepšie pochopenie a určenie, v ktorých frekvenčných pásmach je zmena najdôležitejšia, boli urobené porovnania medzi vypnutou a zapnutou DBS pomocou korelačnej metódy a indexu fázového posunu. Jedenásť pacientov s PD a naimplantovanými neurostimulátormi z firiem Medtronic a St.Jude Medical bolo predmetom nahraných dát použitých v tejto práci. Výsledky dokazujú, že zmena konektivity počas DBS nastane a zároveň, že najviac ovplyvňuje najvyššie frekvencie ako beta, nízka gama a vysoká gama. Zmeny v týchto frekvenciách, zodpovedné za motorickú aktivitu, sústredenie a spracovanie informácií, sú v súlade s klinickou teóriou o PD. Počas tejto choroby je patologická beta aktivita hypersynchronizovaná a gama aktivita je znížená práve v motorických oblastiach. Ak sa gama aktivita počas zapnutej stimulácie zvyšuje, fyziologický stav pacientov sa čiastočne znovuobnovuje a tým zlepšuje ich hybnosť. Metódy a výsledky tejto práce budú použité pre ďalší výskum pacientov s PD a epilepsiou.

Huntington's disease (HD) and Parkinson's disease (PD) are devastating neurodegenerative diseases that progress with the death of selective neuronal subpopulations. Neuronal dysfunction and death are consequence of multiple pathogenic processes which alter signalling cascades. The identification of such molecular pathways is crucial to understand the cellular processes that triggers the symptomatology of diseases. One of the common affected pathways in neurodegeneration is the mTOR pathway. It regulates multiple cellular processes to preserve cellular viability and function. Consequently, to maintain a proper function mTOR activity needs to be fine-tuned. RTP801 is an mTOR negative regulator whose action over this pathway plays a significant role in neurodegeneration. RTP801 protein is induced in an attempt to cope cellular stress. However a sustained RTP801 increase leads to neuronal death by sequentially inactivating first mTOR and then Akt pro-survival kinase. RTP801 pathological increase has been involved in neurodegenerative diseases such as PD. Therefore, identifying RTP801 as a possible new therapeutic target in HD would be highly valuable in designing new pharmacological therapies that block, or at least delay, the neurodegeneration and changes in synaptic plasticity associated with it. Our results show that the overexpression of pathogenic N-terminal htt increases RTP801 levels by both lengthening the protein half-life and up-regulating its gene expression. Blockade of RTP801 expression prevents mhtt-induced cell death in HD cellular models. Importantly, RTP801 is elevated in HD-iPSC and putamen, caudate nucleus and cerebellum of human HD post-mortem brain. Although total RTP801 levels in the striatum of HD murine models are not altered, RTP801 is increased in the synaptic compartment which contributes to motor learning deficits in the R6/1 model. Downregulation of striatal RTP801 preserves motor learning skills in R6/1 mice. Hence, RTP801 is identified as a novel downstream effector of mhtt which mediates its toxicity. Recently, exosomes have emerged as a key mechanism to maintain trophic support between neural cells and as vehicle for the clearance of toxic proteins from neurons. Since RTP801 is upregulated under stressful conditions, its propagation by exosomes may allow the neuron-to-neuron spreading of RTP801 toxicity through the modulation of mTOR/Akt pathway. Our results have elucidated a novel function of RTP801 as an exosomal protein. We demonstrate that both ectopic and endogenous RTP801 can be found in exosomes derived from HEK293 cells. In cortical neurons, exosomal RTP801 elevation is sensitive to PD mimetic 6-OHDA (6-hydroxydopamine) but not to potassium depolarization. Consequently, 6-OHDA exposure induces the loading of RTP801 into exosomes released from cortical neurons. Intriguingly, mhtt does not elevate RTP801 in exosomes obtained from a cellular model. In addition, we demonstrate that exosomes have a protective role promoting the activation of both mTOR complex 1 and 2 in recipient neurons, but increased RTP801 counteracts exosomal mTOR pathway activation suggesting that RTP801 negatively modulates pro-survival signals transneuronally. Altered protein functions of the mTOR pathway are a common hallmark in many neurodegenerative diseases. However, little is known about the contribution of genetic variants or single nucleotide polymorphisms (SNPs) that belong to the mTOR pathway. As a multifactorial disease, we studied the association of SNPs in genes encoding mTOR pathway protein components with the susceptibility PD and the response to levodopa (L-DOPA) treatment. The data found indicate that polymorphisms in genetic markers of the mTOR pathway contribute to the susceptibility to PD and the response to L-DOPA treatment in PD patients. We show that these SNPs influence the outcome individually or interacting epistatically with other genetic markers. Taken together, our findings indicate that deregulation of the mTOR signalling pathway plays an important role in the pathogenesis associated with PE and HD and its regulation is crucial to maintain adequate neuronal function and viability.
La enfermedad de Huntington (EH) y la enfermedad de Parkinson (EP) son enfermedades neurodegenerativas devastadoras caracterizadas por la muerte de subpoblaciones neuronales selectivas. La disfunción neuronal y la muerte son consecuencia de múltiples procesos patogénicos que llevan a la alteración de cascadas de señalización. Una de las vías afectadas de forma común en los procesos neurodegenerativos es la vía mTOR. Como modulador de numerosos procesos celulares, la vía de mTOR está regulada para mantener la supervivencia neuronal y la plasticidad sináptica. Una de las proteínas que modula esta cascada de señalización es RTP801. RTP801 se induce en respuesta a factores de estrés celular y su aumento desencadena la muerte neuronal al regular negativamente la vía mTOR/Akt. La implicación de RTP801 en la EP ha sido ampliamente estudiada, sin embargo, su contribución a la patogénesis de la EH nunca antes había sido explorada. Específicamente, nuestros resultados han identificado a RTP801 como un mediador de la toxicidad inducida por huntingtina mutada. El aumento de RTP801 medía la muerte celular inducida por huntingtina mutada y contribuye a la disfunción del aprendizaje motor en el modelo murino R6/1. El silenciamiento de RTP801 en el estriado de los ratones R6/1 contribuye a preservar la plasticidad sináptica de la vía corticoestriatal, y por tanto del aprendizaje motor. Por otra parte, mostramos que los exosomas secretados por neuronas activan la vía de supervivencia mTOR/Akt en neuronas recipientes. Sin embargo, ante un estrés celular, la toxicidad de RTP801 es propagada a través de exosomas que contrarrestan la activación trófica de la vía mTOR/Akt. Finalmente, demostramos que variaciones genéticas en los componentes de la vía de mTOR modulan la susceptibilidad y la edad de inicio de la EP y, contribuyen a la aparición y severidad de la discinesia inducida por levodopa. En conjunto, nuestros hallazgos indican que la desregulación de la vía de mTOR desempeña un papel importante en la patogénesis asociada a la EP y la EH y, su correcta regulación es crucial para mantener la viabilidad y función neuronal.

This diploma thesis deals with an analysis of subject’s movement during measurements with funcional magnetic resonance imaging (fMRI). It focuses on methods of a movement artifacts detection and their removal in fMRI images. Thesis deals with metrics which are used for the movement rate of measured subjects evaluation. Metrics and a correction of movement are implemented into the programme in MATLAB. Comparison of subjects suffering from Parkinson’s disease with a group of healthy control was carried out. Tresholds of individual metrics were suggested and a criterion for the removal of subjects with high movement rate was determined.

This project describes design of the system for diagnosis Parkinson’s disease based on speech. Parkinson’s disease is a neurodegenerative disorder of the central nervous system. One of the symptoms of this disease is disability of motor aspects of speech, called hypokinetic dysarthria. Design of the system in this work is based on the best known segmental features such as coefficients LPC, PLP, MFCC, LPCC but also less known such as CMS, ACW and MSC. From speech records of patients affected by Parkinson’s disease and also healthy controls are calculated these coefficients, further is performed a selection process and subsequent classification. The best result, which was obtained in this project reached classification accuracy 77,19%, sensitivity 74,69% and specificity 78,95%.

The diploma thesis deals with the non-invasive analysis of progression of Parkinson´s disease using the acoustic analysis of speach. Hypokinetic dysarthria in connection with Parkinson´s disease as well as speech parameters are described in this work. Speech parameters are sorted according to the speech component they affect. The work uses the phonation of vowels "a" speech task as the most commonly used speech task in the field of pathological speech processing, because of its resistance to demographic and linguistic characteristics of the speakers. Based on obtained knowledge, in MATLAB development enviroment were created systém for UPDRS III scale estimation. The UPDRS III scale is based on subjective diagnosis given by the doctor. At first, one individual parameter is used for the UPDRS III scale value estimation. Then the feature selection using SFFS algorithm is applied to gain feature combination with minimal estimation errror. Attention i salso paid to correlation between individual symptoms and UPDSR III scale.

My thesis is divided into.4 chapters, each dealing with a particular central nervous system disorder. The first chapter is devoted to the understanding of the pathogenesis of Parkinson's disease (PD). Several studies with living or dead patients with PD were performed. Animal experiments relied heavily on the use of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to create an animal model of PD. Two major conclusions of this chapter are firstly, that patients with PD may be exposed up to the time of death to one or more neurotoxins that may act via reactive free radicals,, and secondly, that antioxidant compounds such as α-tocopherol may be useful in slowing the progression of neuronal loss in PD. The second chapter in this thesis tested the hypothesis that the premature neuronal death that occurs in Huntington's chorea (HC) may be the result of a genetically-determined enzymatic failure in the degradation of a circulating neurotoxin of either endogenous or exogenous origin. Two main types of studies were performed: an in vivo experiment in which rats were injected repeatedly with serum or serum ultrafiltrate from HC patients or control subjects, and, an in vitro study in which rat striatal explants were exposed in tissue culture to serum or CSF from patients or controls. The results from both types of experiments are suggestive for the presence of a neurotoxin in the serum of patients with HC. This putative neurotoxin may either be a small molecule irreversibly bound to serum proteins, or, a molecule larger than 10000 daltons. The identity of the putative neurotoxin is presently unclear. In the third chapter of this thesis, we examined for neurochemical abnormalities that might be present in the autopsied brains of patients who died with dialysis encephalopathy (DE). A major finding was a deficiency of GABA contents in several regions of autopsied brains of DE patients. Aluminum levels were abnormally high in the frontal cortical gray matter of DE patients. Animal experiments were unsuccessful in clarifying whether or not aluminum is the causative factor in DE, principally because we failed to produce elevation of aluminum content in the brains of rats injected with aluminum hydroxide. The latter was the case even though we employed hemi-nephrectomy, 5/6 nephrectomy, and/or chronic lithium administration in attempts to decrease the renal excretion of aluminum. Finally, in the fourth chapter, we searched for neurochemical abnormalities in the autopsied brain of 2 patients who died with a rare disease, Hallervorden-Spatz syndrome (HSS). In one patient, contents of cystine and of glutathione-cysteine mixed disulfide in the globus pallidus were elevated 2 SD above those of controls. On the other hand, activity of cysteine dioxygenase, the enzyme that converts cysteine to cysteine sulfinate, was reduced in the globus pallidus of both patients. We propose the hypothesis that cysteine accumulates locally in the globus pallidus in HSS as a result of decreased activity of cysteine dioxygenase. Accumulated cysteine may serve to chelate iron, accounting for the local increase in iron content in the1globus pallidus of HSS. The combination of iron and cysteine may generate free radicals that damage neuronal membranes to cause the typical morphological changes observed in HSS.
Medicine, Faculty of
Anesthesiology, Pharmacology and Therapeutics, Department of
Graduate

La adenosina es un metabolito presente en todo el organismo con distintas funciones fisiológicas. En el sistema nervioso central, desempeña un importante papel como neuromodulador a través de la interacción con sus receptores de membrana: los receptores de adenosina A(1), A(2A), A(2B) y A(3), siendo los más abundantes en el cerebro el A(1 )y el A(2A). El receptor de adenosina A(2A) (A(2A)R) presenta una elevada expresión en el estriado, especialmente en las neuronas GABAérgicas medianas espinosas que conforman la vía indirecta de los ganglios basales. La actividad de esta vía está relacionada con la inhibición motora. La actividad del A(2A)R puede modular de hecho la actividad motora. Es bien conocido cómo, tanto en modelos animales como en humanos, los antagonistas del receptor, como la cafeína, estimulan el movimiento, mientras que sus agonistas tienen actividad sedante. Las tres enfermedades abordadas en este trabajo han sido previamente relacionadas con alteraciones del sistema adenosinérgico. En la enfermedad de Parkinson, coincidiendo con una sintomatología hipocinética, se ha descrito una sobreexpresión patológica del A(2A)R en el estriado. La reducción de los niveles del receptor ha sido descrita en la misma región cerebral en el contexto de la enfermedad de Huntington, en la que se da una sintomatología hipercinética. La esquizofrenia, a su vez, ha sido relacionada con una disfunción de los ganglios basales y un déficit en la señalización adenosinérgica. La línea de investigación en la que se enmarca este trabajo había determinado previamente cómo la expresión tejido específica del A(2A)R en el cerebro está controlada por la metilación de la región 5'UTR de su gen, ADORA2A. A lo largo de la presente tesis se ha investigado si éste u otros mecanismos epigenéticos están implicados en la aparición de niveles anómalos del receptor en las enfermedades de Parkinson y Huntington. Además, se han explorado los niveles de expresión del receptor en el estriado en personas con esquizofrenia. Para todo ello se ha trabajado fundamentalmente con muestras de putamen postmortem, una de las regiones del estriado que ha sido vinculada más estrechamente con el control motor. Este trabajo ha permitido confirmar que la sobreexpresión patológica del A2A en el estriado en la enfermedad de Parkinson se produce ya en los primeros estadios de la enfermedad (estadios de Braak 1 a 3), coincidiendo con una bajada de los niveles del microARN hsa-miR-34b. El descenso en los niveles de este microARN había sido previamente descrito en cerebros postmortem de personas con Parkinson pero en otras regiones cerebrales, relacionándolo con estrés mitocondrial. En este trabajo se ha validado el A(2A)R como diana para este microARN mediante ensayos funcionales in vitro, por lo que se propone que el descenso del hsa-miR-34b promueve un aumento de los niveles del A(2A)R en el putamen desde las primeras etapas de la progresión patológica. En cuanto a los resultados en la enfermedad de Huntington, se ha mostrado cómo la reducción de la expresión del A(2A)R en el estriado humano coincide con un incremento en los niveles de metilación y una reducción en los niveles de hidroximetilación de la región 5'UTR del ADORA2A. El estudio llevado a cabo en la esquizofrenia ha revelado un importante descenso de la expresión del A(2A)R en la mitad de los casos patológicos analizados, coincidiendo con hipermetilación de la región 5'UTR del ADORA2A. Estos casos presentan además una sintomatología motora particular, lo que ha permitido proponer la existencia de un subgrupo de pacientes en esta enfermedad. Esto resultados ofrecen soporte a ciertas estrategias terapéuticas propuestas para estas enfermedades y basadas en la modulación de la actividad o de la expresión del A(2A)R. Indican además un uso potencial para la medida de los niveles del A(2A)R en los pacientes con trastorno motor. Esta información permitiría una mayor personalización de los tratamientos y una mejora en la interpretación de las respuestas individuales a los fármacos.
Adenosine is a metabolite distributed throughout the entire organism with multiple physiological functions. In the central nervous system it plays a main role as neuromodulator, interacting with specific membrane receptors: A(1), A(2A), A(2B) and A(3). The most brain-enriched are A1 and A2A. Adenosine receptor A(2A) (A(2A)R) is highly expressed in the striatum, specially in the GABAergic medium-sized spiny neurons that form the indirect pathway of the basal ganglia, whose activity has been related with motor inhibition. There is evidence for A(2A)R activity involvement in motor behavior: A(2A)R antagonists, as caffeine, stimulate locomotion, while A(2A)R agonists are sedative. The three diseases studied in this work have previously been related to adenosinergic system dysfunction. In Parkinson's disease, characterized by hypokinesia, a pathological overexpression of striatal A(2A)R has been described. In Huntington's disease, characterized by hyperkinesia, striatal A(2A)R expression is reduced. Schizophrenia has been related to basal ganglia dysfunction and reduced adenosinergic signaling. In previous studies, the group described how DNA methylation regulates ADORA2A (A(2A)R gen) basal expression in different cell lines as well as its tissue-specific expression in brain. In the present thesis, it was studied whether this or other epigenetic mechanisms were involved in A(2A)R pathological expression levels detected in Parkinson or Huntington diseases. Besides, A(2A)R levels were analyzed in striatum of schizophrenia patients. The work has been performed mainly using human postmortem putamen samples, a striatal region strongly related to motor control. Overall, the obtained results (i) reinforce the relation between A(2A)R striatal expression and motor control, (ii) demonstrate involvement of epigenetic mechanisms in pathological A(2A)R expression in different neuropathological contexts and (iii) support therapeutic strategies previously proposed based on the modulation of A(2A)R expression, and indicate potential usefulness of A(2A)R levels measure in patients with motor alterations, considering that this information would allow a better personalization of treatments and a better understanding of individual reactions to drugs.

The reach-to-eat movement, in which a hand is advanced towards a food item, shapes to grasp the food item, and withdrawals to place the food item into the mouth for eating, is a behaviour that is performed daily. The movement is controlled by two sensory systems, vision to guide hand advance and grasping, and somatosensation to guide hand withdrawal and mouth placement. The purpose of the present thesis was to examine how the sensory control of reaching-to-eat develops in infancy and degenerates following neurodegenerative disorder. The tight coupling of vision to hand advance and somatosensation to hand withdrawal has a developmental profile from six months to one year of age. That is, six-month-old infants rely on vision to advance their hand, grasp the target, and withdrawal the target to the mouth. By twelve months of age, infants display the adult pattern of coupling vision to hand advance and grasping. The tight coupling of vision to hand advance degenerates with basal ganglia disease, such that subjects with Parkinson’s disease and Huntington’s disease show an overreliance on vision to guide hand advance for grasping and hand withdrawal for mouth placement. The results of the thesis demonstrate that efficient use of sensory control to guide motor behaviour is an important aspect of development that is disrupted by neurodegenerative disease.
xiv, 286 leaves : ill. ; 29 cm

Choroba Parkinsona jest jedną z najczęściej występujących chorób neurodegeneracyjnych. Do najbardziej charakterystycznych objawów tej choroby zaliczane są: degeneracja neuronów dopaminergicznych, zmniejszenie poziomu dopaminy, wzrost poziomu wolnych rodników, a także problemy ze snem oraz poruszaniem się. Do modelowania symptomów choroby Parkinsona najczęściej wykorzystywane są neurotoksyny hamujące aktywność pierwszego kompleksu mitochondrialnego bądź mutacje genów kodujących białka biorące udział w mitofagii. W pierwszej części pracy zbadano związek pomiędzy chorobą Parkinsona wywołaną mutacjami genów mul1 oraz park a zaburzeniami pracy zegara okołodobowego u Drosophila melanogaster. Przeprowadzono analizę ekspresji głównych genów zegara (per, tim, clk) oraz białka (PER) w mózgu, a także analizę okołodobowej aktywności lokomotorycznej. Otrzymane wyniki wykazały, że u mutantów mul1 oraz park faza rytmu ekspresji genów zegara jest przesunięta, natomiast rytm ekspresji białka PER jest całkowicie zniesiony, co skutkuje zaburzonym rytmem aktywności lokomotorycznej. Wykazano, że zmiana ta jest następstwem zahamowania autofagii u tych mutantów, a także zwiększonej liczby wolnych rodników w mózgu oraz zmniejszeniem poziomu SOD1. W kolejnej części wykazano, że nadekspresja genów kodujących białka MUL1 oraz PARK w neuronach hamuje rozwój choroby Parkinsona wywołanej rotenonem. Wykonano analizę liczby neuronów dopaminergicznych, wyznakowanych immunohistochemicznie, zbadano poziom białek synaptycznych biorących udział w egzocytozie neuroprzekaźników (analiza Western Blot), zanalizowano błonę presynaptyczną w celu zbadania morfologii stref aktywnych synaps (elektronowy mikroskop transmisyjny), a także zbadano aktywność lokomotoryczną. Uzyskane wyniki wykazały, że szczepy z nadekspresją mul1 i park nie wykazują degeneracji neuronów dopaminergicznych po podaniu rotenonu, poziom badanych białek synaptycznych nie ulega zmniejszeniu, a strefy aktywne w elementach presynaptycznych nie posiadają żadnych nieprawidłowości. Ponadto aktywność motoryczna badanych osobników ulega poprawie. Wykazano, że obserwowane efekty są związane z obniżeniem poziomu apoptozy oraz zwiększeniem poziomu autofagii i poziomu białka SOD1. Stwierdzono również, że mutacja genu kodującego kinazę mitochondrialną PINK1 powoduje zaburzenia w morfologii i funkcjonowaniu synaps, podobne do obserwowanych na modelach wywołanych rotenonem.
Parkinson's disease is one of the most common neurodegenerative diseases worldwide. The most characteristic symptoms of this disease include loss of dopaminergic neurons, reduction of dopamine levels, increase of free radicals level, and problems with sleep and movement. Neurotoxins, which inhibit activity of the first mitochondrial complex or mutations of genes encoding proteins involved in mitophagy, are the most frequently used to model symptoms of Parkinson's disease. In the first part of this work, we examined the link between the Parkinson's disease caused by mutations of mul1 and park genes and circadian rhythmic disorder in Drosophila melanogaster. The circadian rhythm of locomotor activity depends on the cyclic expression of the main clock genes (per, tim) and protein (PER) in the brain. Flies with mu1l or park mutations showed half an hour phase shift of clock gene expression while the rhythm of PER protein expression was completely abolished. This resulted in disruption of locomotor activity rhythm. Our results suggest that observed changes are a consequence of the suppression of autophagy, as well as an increased number of free radicals in the brain and reduction of SOD1 level. We also showed that overexpression of genes encoding MUL1 and PARK proteins in neurons suppresses development of rotenone-induced Parkinson's disease. The number of dopaminergic neurons was evaluated using immunohistochemistry. Western Blot analysis was used to investigate the level of synaptic proteins involved in neurotransmitter exocytosis. Using a transmission electron microscope, the presynaptic membrane was visualized and examined. The negative geotaxis test was carried out to evaluate motor activity. The conducted studies showed that mul1 or park overexpressing strains do not show dopaminergic neuron degeneration after administration of rotenone, the level of synaptic proteins was not reduced, active zones in the presynaptic elements did not have any abnormalities and motor activity of flies was improved. Our results suggest that these effects may result from decreased level of apoptosis and increased autophagy and SOD1 protein level. We also found that mutation of the gene encoding the mitochondrial kinase PINK1 also causes synaptic and motor disorders similar to those observed in the previously described rotenone-induced models.

This dissertation is a collection of a total of seven publications that deal with eye movement disorders in patients with basal ganglia disorders. We obtained normative data for videooculography in healthy individuals. We have described the eye movement evolution during a human life such as the increase of latency, movements become hypometric and antisaccadic error rate increases. We have shown that sex and education do not affect the eye movements. Our study highlighted the asymmetry in the eye movement performance. As the first, we studied the vergence in patients with Parkinson's disease (PN) using videooculography (VOG). We devised and defined a paradigm for this examination and saw that in patients with PN there is a prolonged latency and hypometry of divergence. In patients with ephedrone induced parkinsonism (EP), we were the first who examined eye movements and found that it was possible to identify between this toxic Parkinson's syndrome and PN on the basis of a videooculography. In EP patients, we described velocity decsrease and hypometry in horizontal saccades, prolonged latency in horizontal saccades, and higher error rate in the antisacadic task. Behavioral disorder in REM sleep (RBD) as a prodromal stage of PN leads to impaired eye movement. In the evaluation with PN patients, we...

Title: An electromyographical analysis of the influence of water environment on the rehabilitation of patients with Parkinson's disease Aims: The main aim of this Master's thesis was to compare electrical activity of selected muscles of patients with Parkinson's disease via electromyography during gate aground and in water environment. Furhter aim was to determine co-contraction level of leg muscles of patients with Parkinson's disease during gait aground and in water environment. Methods: This thesis is a case study, which was conducted on five probands, two of which were men and three women of age 67,4±7,1. With the use of surface electromyography, an activity was evaluated of m.tibialis anterior, m.gastrocnemius, m. rectus femoris, m. biceps femoris and mm. erectores spinae in place of Th -L junction. Acquired EMG signal was analized and then a standarized level of muscle activity during gait in different environments was evaluated, aground and in water, and afterward a dynamic co-contraction level was evaluated. Results: The results show consistent standardized activity of monitored muscles in water environment, which describes a chronic influence of pathological central program accompanying Parkinson's disease, where a change in coordination pattern is not observed, typical for movement in...

This diploma thesis is focused on providing speech therapy intervention for seniors in residential facilities. The aim of this special pedagogical work is to show the problems in the communication of seniors and a possible support in the home for the elderly. The thesis has two parts. The theoretical part is divided into three chapters. In this part, secondary communication disorders observed among adults, selected diseases related to old age, the definition of old age and residential services for seniors are described. In the empirical part, the research, case studies and the results are obtained. The research is qualitative. The main goal was to analyze providing speech therapy intervention in the home for the elderly. Partial goals were to find out whether there would be a progress in the senior communication based on speech therapy intervention and to find out whether the support of home workers in cooperation with an expert can help in this regard as well. Another goal was to elaborate case studies. KEYWORDS Speech therapy intervention, senior, secondary communication disorder, dementia, Alzheimer's disease, Parkinson's disease, retirement home

Title: Kinesiophobia, her predictors and consequences in selected chronic diseases - theoretical review Objectives: To review the issue of the occurrence of kinesophobia in various chronic diseases and to identify its predictors. Methods: The diploma thesis was prepared in the form of a literature search using electronic resources of the National Medical Library, the Central Physical Education Library and professional databases Pubmed, EBSCO, SCORPUS, Medline, Web of Science. The first half of the work summarized all the theoretical background and knowledge of kinesophobia and selected chronic diseases. The second half was focused on the processing of the issue of kinesophobia in selected chronic diseases and on the mapping of their predictors. Results: Based on the processing of available resources dealing with the issue of kinesophobia in selected chronic diseases, a comprehensive overview was created. In patients with chronic low back pain, high levels of kinesophobia were most often associated with chronic pain, functional impairment associated with the disease, obesity, low levels of education, and emotional states (anxiety, depression). In coronary heart disease, high levels of kinesophobia were associated with a lack of understanding of the need for physical activity, social support,...