Dissertations / Theses on the topic 'Preoptic hypothalamus'

Mice display robust and stereotyped behaviors towards pups: virgin males typically attack pups, while virgin females and sexually experienced males display parental care. I show here that virgin males that are genetically impaired in vomeronasal sensing do not attack pups and are parental, suggesting a key role of the vomeronasal system in controlling male infanticide. In addition, we have identified putative vomeronasal receptors (or receptor groups) for the detection of pup odors, thus uncovering new tools for the molecular and genetic dissection of male infanticide. Further, we have uncovered galanin-expressing neurons in the medial preoptic area (MPOA) as key regulators of male and female parental behavior. Genetic ablation of MPOA galanin- neurons results in dramatic impairment of parental responses in both virgin females and sexually experienced males. In addition, optogenetic activation of these cells in virgin males suppresses infanticide and induces pup grooming. Thus, MPOA galanin-expressing neurons emerge as an essential node of regulation of innate behavior in the hypothalamus that orchestrates male and female parenting while opposing vomeronasal circuits underlying infanticide. Our results provide an entry point for the genetic and circuit-level dissection of mouse parental behavior and its modulation by social experience.

The hypothalamic-pituitary-adrenal (HPA) axis is a critical mediator of the stress response system. However, despite clear evidence for an inhibitory role of testosterone on stress-induced activation of the HPA axis, the routes and mechanisms have not been addressed. To first determine where testosterone acts in the brain to regulate stress-related input to the HPA axis, I used a combined retrograde transport and immunohistochemical procedure to characterize the anatomical nature by which androgen targets in the brain communicate with the paraventricular nucleus (PVN) of the hypothalamus, the initial point of the neuronally mediated stress response. The findings suggest that androgens could act throughout the brain, and on a large assortment of brain regions that innervate the PVN. Among the brain regions identified, neurons of the medial preoptic nucleus (MPN), highly express androgen receptors and project abundantly to the PVN, suggesting that the MPN stands out as a potential site of integration between testosterone and the HPA axis. To test the functional role of these cells, I tested whether lesions of the MPN alter the inhibitory effects of testosterone on the HPA axis. By selectively removing cells in the MPN, testosterone regulation of the PVN and HPA axis was eliminated. Together, these findings demonstrated that the integrity of the MPN is essential in maintaining the regulatory effects of testosterone on the brain's response to stress. Finally, to clarify whether the MPN is the seat of, or an obligatory relay for the central effects of testosterone, I tested the effects of implanting the androgen receptor antagonist hydroxyflutamide into the MPN, on the stress-induced activation of the PVN and HPA output. The differential effects of androgen exposure in the MPN on the biosynthetic capacity and activational responses of the PVN and its extended circuitries suggested that the MPN is capable of bridging converging limbic influences to the HPA axis with changes in gonadal status.<br>Medicine, Faculty of<br>Graduate

Les mâles sexuellement expérimentés présentent des modifications à long terme de l'arborisation dendritique, de modifications épigénétiques ainsi qu'une augmentation des niveaux d'expression de protéines associées à la neurotransmission glutamatergique et à la microglie dans l'aire pré-optique médiane (mPOA). En revanche, les concentrations plasmatiques et hypothalamiques en hormones stéroïdes ainsi que les propriétés du système nitrergique, connues pour être modulés par l'expérience sexuelle chez le rat, ne sont pas modifiées. Dans un second temps, l'implication de la voie de signalisation ERK1/2 dans la réponse comportementale associée à l'expérience sexuelle a été étudiée. Nous avons montré que cette voie de signalisation, activée dans la mPOA lors de l'accouplement, est potentialisée par l'expérience sexuelle. Nous avons ensuite démontré que son activation est possible par une action rapide (30 minutes) des stéroïdes. Enfin, nous avons montré que l'inhibition de la voie ERK1/2 avant un premier accouplement n'altère pas la mise en place de l'expérience sexuelle mais diminue de façon réversible la motivation sexuelle des mâles. Ainsi, l'expérience sexuelle est à l'origine de modifications structurales et biochimiques à long terme de la mPOA. Ces modifications, différentes de celles connues chez le rat, sont associées à une potentialisation de la voie de signalisation ERK1/2 activée de façon transitoires durant l'accouplement. Ces résultats mettent en évidence la nécessité d'élaborer un nouveau modèle, différent de celui établi chez le rat, permettant d'expliquer l'amélioration comportementale associée à l'expérience sexuelle chez la souris mâle<br>Sexually experimented males exhibit long term modifications of the dendritic arborization, epigenetic modifications and increased levels of microglia and glutamate associated protein within the hypothalamic medial preoptic area (mPOA). However, hypothalamic and plasmatic concentration of steroid hormones and the nitrergic system are not impacted, contrary to data obtained in rat.The involvement of the ERK1/2 signaling pathway in the induction of sexual experience has also been studied. We showed that ERK1/2 pathway was activated within the mPOA during mating. This activation was increased in sexually experienced males. Furthermore, we showed ex vivo on hypothalamic slices that sex steroids were capable of rapidly (30 min) activate this pathway. Finally, the inhibition of ERK1/2 phosphorylation before the first mating did not disrupt the induction of sexual experience but decreased sexual motivation in a reversible manner.Taken together, these results indicate that long lasting and transitory plasticity mechanisms leading to sexual experience are different between rat and mouse. This indicate the necessity to elaborate a new molecular model associated with the behavioral improvement induced by sexual experience in male mouse

Orientador: Arielle Cristina Arena<br>Resumo: Os anti-inflamatórios não esteroidais (AINEs), entre eles o Ibuprofeno, são amplamente utilizados para o tratamento da dor e de processos inflamatórios, e estão entre as classes de medicamentos mais utilizadas por gestantes. Através da inibição da enzima ciclo-oxigenase, os AINEs inibem a síntese de prostaglandinas, compostos eicosanoides que atuam não somente como mediadores e moduladores inflamatórios, mas também em diversos processos fisiológicos do organismo, como no mecanismo de diferenciação sexual hipotalâmica. O processo de masculinização do hipotálamo é dependente de testosterona, que por ação da enzima citocromo P450 aromatase, é convertida em estradiol. Este hormônio regula positivamente a expressão da enzima ciclo-oxigenase no hipotálamo, aumentando a produção de prostaglandina do subtipo E2 (PGE2), que atua aumentando a formação de espinhas dendríticas no núcleo sexualmente dimórfico da área pré-optica (SDN-POA). Em virtude da importância da PGE2 no processo de diferenciação sexual hipotalâmica, torna-se preocupante o uso de anti-inflamatórios durante a gestação. Desta forma, o objetivo desse estudo foi avaliar os possíveis efeitos resultantes da exposição in utero e lactacional ao ibuprofeno e suas repercussões tardias sobre parâmetros reprodutivos masculinos em ratos machos. Para tanto, ratas prenhes foram expostas a três doses de ibuprofeno (10; 30; 60 mg/kg) entre a última semana de prenhez (Dias gestacionais 15-21) até o final da lactação (Dias pós-natal 21)... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Non-steroidal anti-inflammatory drugs (NSAID), including Ibuprofen, are widely used in the treatment of pain and inflammatory processes, and are of the most commonly classes of drugs used by pregnant women. By inhibiting the cyclooxygenase enzyme (COX), NSAID inhibit the synthesis of prostaglandins, eicosanoids compounds that act not only as mediators and inflammatory modulators, but also in various physiological processes of the organism, such as in the mechanism of sexual hypothalamic differentiation. The hypothalamus masculinization process is testosterone dependent, which by action of the aromatase cytochrome P450 enzyme is metabolized to estradiol. This hormone upregulates the expression of COX enzyme in the hypothalamus, increasing the production of prostaglandin E2, which acts by increasing the formation of dendritic spines in the neurons of the sexually dimorphic nucleus of the preoptic area in males (SDN-POA). Due to the importance of prostaglandin E2 in the process of hypothalamic sexual differentiation, the use of anti-inflammatory drugs during pregnancy is of concern. Thus, the aim of this study was to evaluate the possible effects resulting from in utero and lactation exposure to non-steroidal anti-inflammatory ibuprofen and its late repercussions on male reproductive parameters in male rats. For this, pregnant rats were exposed to three doses of ibuprofen (10; 30; 60 mg/kg) between the last week of pregnancy (Gestational Days 15-21) until the end of lactation (P... (Complete abstract click electronic access below)<br>Mestre

Numa primeira etapa, estudamos as conexões da VTA para o complexo VTA-substância negra (SN) utilizando a leucoaglutinina do Phaseolus vulgaris (PHA-L). Estas conexões são substanciais, topograficamente organizadas, com destaque para o pólo caudal da VTA que inerva bilateralmente toda a extensão deste complexo. Numa segunda etapa, estudamos as projeções da VTA para o hipotálamo. A VTA se projeta principalmente para a área pré-óptica lateral e área hipotalâmica lateral, a região subfornical posterior e o núcleo dorsomedial. Foram vistas poucas aposições entre varicosidades PHA-L+ e neurônios imunorreativos para orexina ou para hormônio concentrador de melanina. Por fim, estudamos a colocalização do substrato do receptor de insulina (IRS-1), IRS-1 fosforilado e fosfatidilinositol-3 quinase (PI3K) com tirosina hidroxilase (TH) ou com a subunidade B da toxina colérica (CTb) injetada no estriado. A maioria dos neurônios TH+ da VTA-SN expressa IRS-1; injeções de CTb no estriado resultaram em células duplamente marcadas para CTb/IRS-1, CTb/PI3K e CTb/IRS-1 fosforilado.<br>In a first step, we studied the connections of the VTA to the complex VTA-substantia nigra (SN) using the Phaseolus vulgaris leucoagglutinin (PHA-L). These connections are substantial, topographically organized, especially the caudal pole of the VTA, which innervates bilaterally throughout the length of this complex. In a second step, we studied the projections of the VTA to the hypothalamus. The VTA projected mainly to the lateral preoptic area, lateral hypothalamic area, posterior subfornical region and dorsomedial nucleus. Were observed few appositions between PHA-L+ varicosities and neurons immunoreactive for orexin or melanin-concentrating hormone. Finally, we studied the co-localization of the insulin receptor substrate-1 (IRS-1), IRS-1-phosphorylated and phosphatidylinositol-3 kinase (PI3K) with tyrosine hydroxylase (TH) or cholera toxin B subunit (CTb) injected into the striatum. Most TH+ neurons of the VTA-SN expressed IRS-1; CTb injections in the striatum resulted in cells double-labeled for CTb/IRS-1, CTb/PI3K and CTb/IRS-1 phosphorylated.

Indiana University-Purdue University Indianapolis (IUPUI)<br>Recent studies in anesthetized rats suggest that autonomic effects relating to thermoregulation that are evoked from the preoptic area (POA) may be mediated through activation of neurons in the dorsomedial hypothalamus (DMH). Disinhibition of neurons in the DMH produces not only cardiovascular changes but also increases in plasma adrenocorticotropic hormone (ACTH) and locomotor activity mimicking those evoked by microinjection of muscimol, a GABAA receptor agonist and neuronal inhibitor, into the POA. Therefore, I tested the hypothesis that all of these effects evoked from the POA are mediated through neurons in the DMH by assessing the effect of bilateral microinjection of muscimol into the DMH on the changes evoked by microinjection of muscimol into the POA in conscious rats. In addition, I tested the hypothesis that neurons in the DMH mediate a specific response that is thought to signal through the POA, the activation of the HPA axis evoked by systemic administration of the inflammatory cytokine IL-1β. After injection of vehicle into the DMH, injection of muscimol into the POA elicited marked increases in heart rate, arterial pressure, body temperature, plasma ACTH and locomotor activity and also increased Fos expression in the hypothalamic paraventricular nucleus (PVN), a region known to control the release of ACTH from the adenohypophysis, and the raphe pallidus, a medullary region known to mediate POA-evoked sympathetic responses. Prior microinjection of muscimol into the DMH produced a modest depression of baseline heart rate, arterial pressure, and body temperature but completely abolished all changes evoked from the POA. Microinjection of muscimol just anterior to the DMH had no effect on POA-evoked autonomic and neuroendocrine changes. Inhibition of neuronal activity in the DMH only partially attenuated the increased activity of the HPA axis following systemic injections of IL-1β. Thus, neurons in the DMH mediate a diverse array of physiological and behavioral responses elicited from the POA, suggesting that the POA represents an important source of inhibitory tone to key neurons in the DMH. However, it is clear that the inflammatory cytokine IL-1β must employ other pathways that are DMH-, and possibly POA-, independent to activate the HPA axis.

碩士<br>國立成功大學<br>生理學研究所<br>81<br>In free moving rats, change in release of monoamine and monoamine metabolites from preoptic anterior hypothalamic area (POAH)were examined in relation to the ambient temperature(Ta). Microdialysis probes were used for the isolated perfusion.When the Ta decreased from room temperature to cold room, the release of 5-HIAA and DOPAC increase in POAH,and decreased in hight room temperature. There was an insignificant change in the release of HVA in response to cold or heat exposure.And either perfusion of 5-HT precursor 5-HTP or 5-HT reuptake inhibitor fluoxetine microdialyzed into the hypothalamus evoke arise in Tco as well as arise in the hypothalamic release of 5-HT and 5-HIAA.The results provide further evidence that the serotoninergic and/or dopaminergic activity in POAH of rat's brain mediates the heat production or heat conservation pathway of the central nervous system in the defense against cold.