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Pharmaceuticals 2017, 10(3), 67; doi:10.3390/ph10030067

Hippocampal Proteome of Rats Subjected to the Li-Pilocarpine Epilepsy Model and the Effect of Carisbamate Treatment

1
Departamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP 04039-032 São Paulo, Brazil
2
Unistra, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Faculté de Psychologie, Université de Strasbourg, 67000 Strasbourg, France
3
CNRS, UMR 7364, LNCA, 12 rue Goethe, 67000 Strasbourg, France
4
INSERM U 1129 “Infantile Epilepsies and Brain Plasticity”, 75015 Paris, France
5
Université Paris Descartes, Sorbonne Paris Cité, CEA, 91990 Gif sur Yvette, France
*
Author to whom correspondence should be addressed.
Received: 15 May 2017 / Revised: 26 July 2017 / Accepted: 27 July 2017 / Published: 30 July 2017
(This article belongs to the Special Issue Epilepsy and Neurodegeneration: Current Therapeutic Implications)
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Abstract

In adult rats, the administration of lithium–pilocarpine (LiPilo) reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE). Carisbamate (CRS) possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment. Fifteen adult male Sprague–Dawley rats were used. SE was induced by LiPilo injection. CRS treatment was initiated at 1 h and 9 h after SE onset and maintained for 7 days, twice daily. Four groups were studied after video-EEG control of the occurrence of motor seizures: a control group receiving saline (CT n = 3) and three groups that underwent SE: rats treated with diazepam (DZP n = 4), rats treated with CRS displaying NCS (CRS-NCS n = 4) or motor seizures (CRS-TLE n = 4). Proteomic analysis was conducted by 2D-SDS-PAGE. Twenty-four proteins were found altered. In the CRS-NCS group, proteins related to glycolysis and ATP synthesis were down-regulated while proteins associated with pyruvate catabolism were up-regulated. Moreover, among the other proteins differentially expressed, we found proteins related to inflammatory processes, protein folding, tissue regeneration, response to oxidative stress, gene expression, biogenesis of synaptic vesicles, signal transduction, axonal transport, microtubule formation, cell survival, and neuronal plasticity. Our results suggest a global reduction of glycolysis and cellular energy production that might affect brain excitability. In addition, CRS seems to modulate proteins related to many other pathways that could significantly participate in the epileptogenesis-modifying effect observed. View Full-Text
Keywords: carisbamate; temporal-lobe epilepsy; hippocampus; proteomics; brain activity carisbamate; temporal-lobe epilepsy; hippocampus; proteomics; brain activity
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MDPI and ACS Style

Marques-Carneiro, J.E.; Persike, D.S.; Litzahn, J.J.; Cassel, J.-C.; Nehlig, A.; Fernandes, M.J.S. Hippocampal Proteome of Rats Subjected to the Li-Pilocarpine Epilepsy Model and the Effect of Carisbamate Treatment. Pharmaceuticals 2017, 10, 67.

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