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Time-Dependent Modulation of Mitogen Activated Protein Kinases and AKT in Rat Hippocampus and Cortex in the Pilocarpine Model of Epilepsy

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Abstract

The epileptogenesis may involve a variety of signaling events that culminate with synaptic reorganization. Mitogen-activated protein kinases (MAPKs) and AKT may be activated by diverse stimulus including neurotransmitter, oxidative stress, growth factors and cytokines and are involved in synaptic plasticity in the hippocampus and cerebral cortex. The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. We analyze the phosphorylation profile of MAPKs (ERK1/2, p38MAPK, JNK1/2/3) and AKT by western blotting in the hippocampus (Hip) and cortex (Ctx) of male adult wistar rats in different periods, after pilocarpine induced status epilepticus (Pilo-SE) and compared with control animals. Biochemical analysis were done in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period) and 50 days (chronic period) after Pilo-SE onset. Hence, the main findings include increased phosphorylation of ERK1 and p38MAPK in the Hip and Ctx 1 and 12 h after the Pilo-SE onset. The JNK2/3 isoform (54 kDa) phosphorylation was decreased at 3 h after the Pilo-SE onset and in the chronic period in the Hip and Ctx. The AKT phosphorylation increased only in the Hip during the latent period. Our study demonstrates, in a systematic manner, the profile of MAPKs and AKT modulation in the hippocampus and cerebral cortex in response to pilocarpine. Based in the role of each signaling enzyme is possible that these changes may be related, at least partially, to modifications in the intrinsic neuronal physiology and epileptogenic synaptic network that appears in the MTLE-HS.

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Acknowledgments

Work supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), IBN.Net/CNPq, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Projeto CAPES/PROCAD, Fundação de Apoio à Pesquisa Cientifica e Tecnológica do Estado de Santa Catarina (FAPESC-PRONEX), (Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina—NENASC). Universidade Federal de Santa Catarina (UFSC).

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Authors and Affiliations

  1. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, SC, 88040-900, Brazil

    Mark William Lopes, Fabiano Mendes de Cordova & Rodrigo Bainy Leal

  2. Centro de Neurociências Aplicadas (CeNAp), HU, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Flávia Mahatma Schneider Soares, Nelson de Mello, Jean Costa Nunes & Roger Walz

  3. Escola de Medicina Veterinária e Zootecnia, Universidade Federal do Tocantins, Araguaína, TO, Brazil

    Fabiano Mendes de Cordova

  4. Departamento de Clínica Médica, Hospital Universitário (HU), Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Roger Walz

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  1. Mark William Lopes
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Lopes, M.W., Soares, F.M.S., de Mello, N. et al. Time-Dependent Modulation of Mitogen Activated Protein Kinases and AKT in Rat Hippocampus and Cortex in the Pilocarpine Model of Epilepsy. Neurochem Res 37, 1868–1878 (2012). https://doi.org/10.1007/s11064-012-0797-y

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