Marques-Carneiro José Eduardo, Persike Daniele Suzete, Litzahn Julia Julie, Cassel Jean-Christophe, Nehlig Astrid, Fernandes Maria José da Silva
Departamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Escola Paulista de Medicina, Universidade Federal de São Paulo, SP 04039-032 São Paulo, Brazil.
Unistra, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Faculté de Psychologie, Université de Strasbourg, 67000 Strasbourg, France.
Pharmaceuticals (Basel). 2017 Jul 30;10(3):67. doi: 10.3390/ph10030067.
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 = 3) and three groups that underwent SE: rats treated with diazepam (DZP = 4), rats treated with CRS displaying NCS (CRS-NCS = 4) or motor seizures (CRS-TLE = 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.
在成年大鼠中，给予锂 - 匹鲁卡品（LiPilo）可重现人类颞叶癫痫（TLE）的大多数临床和神经病理学特征。卡立普多（CRS）具有在此模型中改变癫痫发生的特性。实际上，约50%经历LiPilo癫痫持续状态（SE）的大鼠在接受CRS治疗时会出现非惊厥性癫痫发作（NCS）而非运动性癫痫发作。然而，这些效应背后的机制仍不清楚。本研究的目的是对接受LiPilo并在CRS治疗后出现运动性癫痫发作或NCS的大鼠海马进行蛋白质组学分析。使用了15只成年雄性Sprague-Dawley大鼠。通过注射LiPilo诱导SE。在SE发作后1小时和9小时开始CRS治疗，并持续7天，每天两次。在通过视频脑电图控制运动性癫痫发作的发生后，研究了四组：接受生理盐水的对照组（CT = 3）和三组经历SE的大鼠：用 diazepam治疗的大鼠（DZP = 4）、表现出NCS的CRS治疗大鼠（CRS-NCS = 4）或运动性癫痫发作的大鼠（CRS-TLE = 4）。通过二维SDS-PAGE进行蛋白质组学分析。发现24种蛋白质发生了改变。在CRS-NCS组中，与糖酵解和ATP合成相关的蛋白质下调，而与丙酮酸分解代谢相关的蛋白质上调。此外，在其他差异表达的蛋白质中，我们发现了与炎症过程、蛋白质折叠、组织再生、氧化应激反应、基因表达、突触小泡生物发生、信号转导、轴突运输、微管形成、细胞存活和神经元可塑性相关的蛋白质。我们的结果表明糖酵解和细胞能量产生整体减少，这可能会影响脑兴奋性。此外，CRS似乎调节与许多其他途径相关的蛋白质，这些途径可能显著参与所观察到的癫痫发生改变效应。
