Administração repetida de baixas doses de reserpina: um possível modelo para o estudo de déficits cognitivos e motores associados à Doença de Parkinson
Parkinson's disease (PD) is one of the most common neurodegenerative brain disorders and is characterized primarily by a progressive degeneration of dopaminergic neurons nigroestriatais. The main symptoms of this disease are motor alterations (bradykinesia, rigidity, tremor at rest), which can...
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Формат: | doctoralThesis |
Язык: | por |
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Universidade Federal do Rio Grande do Norte
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Online-ссылка: | https://repositorio.ufrn.br/jspui/handle/123456789/17217 |
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Итог: | Parkinson's disease (PD) is one of the most common neurodegenerative brain
disorders and is characterized primarily by a progressive degeneration of dopaminergic
neurons nigroestriatais. The main symptoms of this disease are motor alterations
(bradykinesia, rigidity, tremor at rest), which can be highly disabling in advanced stages
of the condition. However, there are symptomatic manifestations other than motor
impairment, such as changes in cognition, mood and sensory systems.
Animal models that attempt to mimic clinical features of PD have been used to
understand the behavioral and neural mechanisms underlying neurophysiological
disturbance of this disease. However, most models promote an intense and immediate
motor impairment, consistent with advanced stages of the disease, invalidating these
studies for the evaluation of its progressive nature.
The administration of reserpine (a monoamine depletor) in rodents has been
considered an animal model for studying PD. Recently we found that reserpine (in doses
lower than those usually employed to produce the motor symptoms) promotes a memory
deficit in an aversive discrimination task, without changing the motor activity. It was
suggested that the administration of this drug in low doses can be useful for the study of
memory deficits found in PD. Corroborating this data, in another study, acute
subcutaneous administration of reserpine, while preserving motor function, led to
changes in emotional context-related (but not neutral) memory tasks.
The goal of this research was to study the cognitive and motor deficits in rats
repeatedly treated with low doses of reserpine, as a possible model that simulates the
progressive nature of the PD. For this purpose, 5-month-old male Wistar rats were
submitted to a repeated treatment with vehicle or different doses of reserpine on alternate days. Cognitive and motor parameters and possible changes in neuronal
function were evaluated during treatment. The main findings were: repeated
administration of 0.1 mg / kg of reserpine in rats is able to induce the gradual
appearance of motor signs compatible with progressive features found in patients with
PD; an increase in striatal levels of oxidative stress and changes in the concentrations of
glutamate in the striatum were observed five days after the end of treatment; in animals
repeatedly-treated with 0. 1 mg/kg, cognitive deficits were observed only after the onset
of motor symptoms, but not prior to the onset of these symptoms; 0.2 mg / kg reserpine
repeated treatment has jeopardized the cognitive assessment due to the presence of
severe motor deficits. Thus, we suggest that the protocol of treatment with reserpine
used in this work is a viable alternative for studies of the progressive appearance of
parkinsonian signs in rats, especially concerning motor symptoms. As for the cognitive
symptoms, we suggest that more studies are needed, possibly using other behavioral
models, and / or changing the treatment regimen |
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