Chez les mammifères, l’alternance des états de vigilance nécessite la mise en jeu de mécanismes spéci ques qui facilitent les transitions entre l’éveil, le sommeil lent (SL) et le sommeil paradoxal (SP). L’objectif de cette thèse s’inscrit dans l’optique de disséquer chez la souris les processus neuronaux contrôlant l’alternance physiologique entre ces trois états de vigilance. Au cours de cette thèse, nous avons tout d’abord démontré par des approches complémentaires ex vivo et in vivo que le glucose peut favoriser l’endormissement par son action excitatrice directe sur les neurones promoteurs du SL localisés dans l’aire préoptique ventrolatérale (VLPO). Nous avons ensuite, par deux approches méthodologiques di érentes et complémentaires, contribué à préciser le rôle physiologique des neurones exprimant l’hormone de mélano-concentration (MCH) dans la régulation du cycle veille-sommeil, démontrant ainsi qu’en plus de faciliter le déclenchement et le maintien du SP lorsqu’ils sont activés, ils contrôlent certains aspects du SL en favorisant, au cours SL, un SL plus profond ainsi que la terminaison des épisodes de SL. Forts de ces nouveaux résultats supportant une contribution des neurones MCH à la régulation du SL, nous avons déterminé une voie potentielle pouvant sous-tendre cette fonction physiologique à travers leurs projections efférentes sur le VLPO. Nos résultats préliminaires indiquent que la stimulation optogénétique des axones des neurones MCH dans le VLPO favorise le déclenchement d’un état de transition entre SL et SP sans pour autant conduire au SP / In mammals, alternating between vigilance states requires some speci c processes that facilitate transitions between wake, Slow-Wave Sleep (SWS), and Paradoxical Sleep (PS). The objective of this thesis was to decipher, in mice, the neuronal mechanisms that control the alternation between these three vigilance states. During thus thesis, we first demonstrated using complementary ex vivo and in vivo approaches that glucose can facilitate sleep induction by directly exciting sleep- promoting neurons located within the ventrolateral preoptic nucleus (VLPO). Then, by developing two different and complementary approaches, we contributed to clarify the physiological role of melanin-concentrating hormone (MCH)-expressing neurons in sleep-wake regulation. Indeed, in addition to their PS-promoting effect when activated, we found that MCH neurons also contribute to the regulation of some aspects of SWS regulation by favouring the appearance of a deeper SWS and facilitating SWS episodes termination. These new results supporting a role of MCH neurons to SWS regulation led us to investigate a putative pathway underlying such an effect through efferent projections from MCH neurons to the VLPO. Preliminary results suggest that the optogenetic stimulation of axons from MCH neurons within the VLPO could facilitate the appearance of a transition state between SWS and PS without triggering PS onset

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-12-04T20:41:48Z No. of bitstreams: 1 KayoDiogenesDeAzevedoSilva_DISSERT.pdf: 2312119 bytes, checksum: 0a5f0d4a0645de7bdb4ab990bbb4f59d (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-12-07T20:45:07Z (GMT) No. of bitstreams: 1 KayoDiogenesDeAzevedoSilva_DISSERT.pdf: 2312119 bytes, checksum: 0a5f0d4a0645de7bdb4ab990bbb4f59d (MD5) / Made available in DSpace on 2017-12-07T20:45:07Z (GMT). No. of bitstreams: 1 KayoDiogenesDeAzevedoSilva_DISSERT.pdf: 2312119 bytes, checksum: 0a5f0d4a0645de7bdb4ab990bbb4f59d (MD5) Previous issue date: 2017-07-31 / A doen?a de Parkinson (DP) ? uma patologia neurodegenerativa que acomete principalmente indiv?duos do sexo masculino com o avan?ar da idade. A DP se caracteriza por diversos sintomas motores como tremores, bradicinesia, rigidez e altera??es posturais. Al?m destes, sintomas cognitivos como d?ficits de aten??o e mem?ria, dem?ncia e altera??es de humor tamb?m est?o presentes. ? poss?vel perceber marcada mudan?a na arquitetura do sono de pacientes com DP. O horm?nio melatonina sintetizado principalmente pela gl?ndula pineal localizada no Epit?lamo ? considerado um dos horm?nios que induzem a fase de sono dos organismos. Sua a??o ocorre ap?s se ligar a receptores espec?ficos, MT1 e MT2. No presente estudo foram utilizados 15 ratos machos de meia idade (10 meses) da esp?cie Wistar, divididos em dois grupos denominados de Controle (CTR) e Reserpina (RES). Esses animais foram submetidos a um protocolo cr?nico de 20 inje??es de reserpina, com o intuito de criar sintomatologias semelhantes a DP. Durante o protocolo experimental os animais foram avaliados atrav?s de teste de catalepsia. Com o fim do tratamento os animais foram sacrificados e submetidos a procedimento imunistoquimico para identifica??o dos receptores MT1 e MT2 em 5 ?reas do sistema nervoso central relacionadas diretamente com o ciclo do sono e com sintomas mais evidentes da DP, sendo elas, NE, NSQ, VLPO, SN e ZSPV. Nossos resultados mostraram que durante o per?odo de tratamento os animais do grupo reserpina apresentaram consider?vel e progressivo d?ficits motores que se acentuaram nos dias sete, oito, nove e dez de inje??es. Nossas analises imunoistoqu?micas mostraram que ocorre significativa redu??o da express?o de receptores de melatonina nos animais reserpina em todos os n?cleos avaliados, entretanto, novos estudos s?o necess?rios para uma melhor compreens?o do real motivo dessa diminui??o de express?o de receptores e se esta diminui??o tem efeito significativo nas altera??es do sono verificadas nos pacientes com DP. / Parkinson's disease (PD) is a neurodegenerative disorder that mainly affects males with advancing age. PD is characterized by several motor symptoms such as tremors, bradykinesia, stiffness and postural changes. In addition to these, cognitive symptoms such as attention and memory deficits, dementia and mood changes are also present. It is also possible to notice a marked change in the sleep architecture of patients with PD. The hormone melatonin synthesized mainly by the pineal gland located in the thalamus is considered one of the hormones that induce the sleep phase of the organisms. Its action occurs after binding to specific receptors, MT1 and MT2. In the present study, 15 male Wistar rats (10 months) were divided into two groups called Control (CTR) and Reserpine (RES). These animals were submitted to a chronic protocol of 20 injections of reserpine, in order to create symptoms similar to PD. During the experimental protocol the animals were evaluated by catalepsy test. At the end of the treatment the animals were sacrificed and submitted to an immunohistochemical procedure to identify the MT1 and MT2 receptors in 5 areas of the central nervous system related directly to the sleep cycle and with more evident symptoms of PD, VLPO, SN and ZSPV. Our results showed that during the period of treatment the animals of the reserpine group presented a considerable and progressive motor deficit that were accentuated on days seven, eight, nine and ten of injections. Our immunohistochemical analyzes have shown that there is a significant reduction in the expression of melatonin receptors in the reserpine animals in all evaluated nuclei, however, new studies are necessary to better understand the real reason for this decrease in receptor expression and whether this decrease has a significant effect on Observed in patients with PD.