Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-03T22:27:13Z No. of bitstreams: 1 AldairJoseSarmentoSilva_TESE.pdf: 2312100 bytes, checksum: 1301de7c766dd249c7fa5a2b5e60c937 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-04T22:40:33Z (GMT) No. of bitstreams: 1 AldairJoseSarmentoSilva_TESE.pdf: 2312100 bytes, checksum: 1301de7c766dd249c7fa5a2b5e60c937 (MD5) / Made available in DSpace on 2016-02-04T22:40:33Z (GMT). No. of bitstreams: 1 AldairJoseSarmentoSilva_TESE.pdf: 2312100 bytes, checksum: 1301de7c766dd249c7fa5a2b5e60c937 (MD5) Previous issue date: 2014-12-12 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / A doen?a de Parkinson (DP) ? um dist?rbio neurodegenerativo progressivo que afeta aproximadamente de 1-2% da popula??o mundial, com maior preval?ncia entre os homens. Os principais sintomas s?o motores, e incluem bradicinesia, rigidez, instabilidade postural e tremor em repouso. Al?m disso, ocorrem sintomas n?o motores, tais como dist?rbios do sono, ansiedade, depress?o, e d?ficits cognitivos. Tais altera??es cl?nicas s?o consequ?ncia da perda irrevers?vel de neur?nios dopamin?rgicos principalmente na subst?ncia negra parte compacta. O tratamento mais eficaz para a DP ? o uso da levodopa, por?m, esta medica??o trata apenas os sintomas, apresentando limita??es ap?s o uso prolongado. Sendo assim, consideram-se alternativas de tratamento que pudessem conferir neuroprote??o, retardando a progress?o da doen?a e/ou prevenindo o surgimento dos sintomas. Um exemplo seria o uso de antioxidantes, dentre eles, o ?-tocoferol. Os mecanismos, assim como a natureza cr?nica da doen?a, podem ser mimetizados e estudados a partir do uso de modelos animais. Dessa forma, o principal objetivo do nosso estudo foi investigar os efeitos da administra??o do ?-tocoferol sobre os danos motores, cognitivos e neuronais em um modelo animal para doen?a de Parkinson. Utilizamos a administra??o repetida de uma dose baixade reserpina, concomitante com a aplica??o de ?-tocoferol. N?s observamos que o tratamento repetido com reserpina provocou d?ficits cognitivos e motores de forma progressiva, al?m de uma diminui??o na marca??o para a enzima tirosina hidroxilase (envolvida na s?ntese de dopamina) na via nigroestriatal. No entanto, esses d?ficits n?o foram apresentados pelo grupo de animais tratados com ?-tocoferol, evidenciando um prov?vel efeito neuroprotetor provacado pelo antioxidante. Podemos concluir que a aplica??o de ?-tocoferol foi capaz de previnir as altera??es causadas pela administra??o de reserpina. Ainda, o nosso estudo sugere que a indu??o de danos motores e cognitivos progressivos pela reserpina quando aplicada em baixas doses s?o adequados para o estudo de poss?veis interven??es neuroprotetornas para a DP. / Parkinson?s disease (PD) is a progressive neurodegenerative disorder that affects 1-2% of world population, with a higher prevalence among men. The main symptoms are of motor nature, and include bradikynesia, rigidity, postural instability and tremor. In addition, non-motor symptoms may occur, such as sleep disturbances, anxiety, depression, and cognitive deficits. The motor alterations are a consequence of the irreversible loss of dopaminergic neurons mainly in the substantia nigra pars compacta. The most effective current treatment for PD is L-DOPA administration. However, this drug, despite amegliorating symptoms, does not interfere with the neurodegeneration, and thus has limitations at long term. Thus, alternative treaments that could act by neuroprotective mechanisms have been considered, such as antioxidant agents. The mechanisms related to the symptoms and progressive nature of PD can be studied in animal models. In this sense, the aim of the present study was to investigate the effects of the antioxidant ?-tocopherol on the motor, cognitive and neuronal deficits induced by repeated treatment with reserpine (a progressive pharmacological model of parkinsonism). Rats submitted to the reserpine protocol were concomitantly treated with ?-tocopherol. The results showed that the repeated treatment with reserpine, as expected, induced progressive motor and cognitive decrements, as well as dimished tyrosine hydroxylase immunostaining in the substantia nigra pars compacta and striatum. These deficits were not present in the animals that were co-treated with ?-tocoferol, suggesting a possible neuroprotective effect induced by this antioxidant agent. In conclusion, ?-tocoferol was able to prevent the alterations caused by repeated reserpine administration. In addition, our study suggest that low-dose reserpine-induced progressive motor and cognitive deficits can be useful in the study of possible neuroprotective strategies for PD.