Physical activity and neuroprotection in adult mice after pilocarpine induced status epilepticus / Atividade fisica e neuroproteção em camundongos adultos após indução de status epilepticus por pilocarpina
AUTOR(ES)
Cesar Renato Sartori
DATA DE PUBLICAÇÃO
2005
RESUMO
Pilocarpine-induced epilepsy in mice is an experimental model of the Temporal Lobe Epilepsy (TLE). Status epilepticus determined by pilocarpine adminstration leads to behavioral and electroencephalographic changes and neuronal damage similar to those observed in TLE. Recently, it has been shown that physical activity exerts neuroprotective effects, such as increase in neuronal survival, angiogenesis and neurogenesis; resistance to brain injuries, strengthening of the long term potentiation (LTP), improvement of memory and learning; and preservation of cognitive function during aging process. Particularly, physical activity also plays a positive role in epileptic patients and animals. However, there are no reports regarding the neuroprotective action of physical activity on the pilocarpine model of epilepsy in mice. In the present work, we studied the effects of the voluntary physical activity on hippocampal neuronal loss and mnemonic function of mice after the pilocarpine-induced status epilepticus. Thirty-two Swiss mice were assigned to four experimental groups (n=8): Normal Sedentary (NS), Normal Runner (NR), Epileptic Sedentary (ES) and Epileptic Runner (ER). Forty-eight hours after the status epilepticus or its simulation the animals of the runner groups (NR, ER) had access to a running wheel for 28 days. After that, the mice were submitted to the Morris Water Maze test for the evaluation of the spatial memory. Finally, the mice were perfused with paraformaldehyde (4% in phosphate buffer), the brains were dissected and processed for paraffin embedding. Frontal sections (8mm) were serially cut and used for analysis of histologic damage (Nissl staining), degenerating neurons (Fluoro Jade B) and cell proliferation (immunohistochemistry for PCNA) of the dorsal hippocampal formation. Mice of the NS and NR groups showed neither neuronal damage nor neurodegeneration. In addition, these groups were similar to each other in the Morris Water Maze test and exhibited comparable immunostainig patterns for PCNA. In contrast to the previous groups, in ES and ER groups neuronal damage and neurodegeneration were observed and equivalent. However, cell proliferation was higher in ES than in ER. Animals of the ER group had better performance in the Morris Water Maze test compared to ES mice. In conclusion, our results show that physical activity improved significantly the spatial memory of mice that had status epilepticus induced by pilocarpine, despite of having not changed the morphological evidence of neuronal damage. We believe that such improvement might be attributed to molecular mechanisms related to neuronal plasticity, which were not identified by the techniques we used in the present investigation.
ASSUNTO(S)
atividade fisica neuroprotective agents epilepsy physical activity epilepsia mice camundongo pilocarpine
ACESSO AO ARTIGO
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