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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.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/19766 |
| Date | 12 December 2014 |
| Creators | Silva, Aldair Jos? Sarmento |
| Contributors | 18747270829, http://lattes.cnpq.br/0101190051087933, Ribeiro, Alessandra Mussi, 26403824899, http://lattes.cnpq.br/7373640456805525, Gavioli, Elaine Cristina, 97013390968, http://lattes.cnpq.br/1759328747578795, Cavalcante, Jeferson de Souza, 70317232487, http://lattes.cnpq.br/2378505945149958, Abilio, Vanessa Costhek, 25106474825, http://lattes.cnpq.br/2393173678667897, Silva, Regina Helena da |
| Publisher | Universidade Federal do Rio Grande do Norte, PROGRAMA DE P?S-GRADUA??O EM DESENVOLVIMENTO E INOVA??O TECNOL?GICA EM MEDICAMENTOS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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