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Effects of Pentylenetetrazole Kindling on Mitogen-Activated Protein Kinases Levels in Neocortex and Hippocampus of Mice

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Abstract

The epileptogenesis process involves cell signaling events associated with neuroplasticity. The mitogen-activated protein kinases (MAPKs) integrate signals originating from a variety of extracellular stimuli and may regulate cell differentiation, survival, cell death and synaptic plasticity. Here we compared the total and phosphorylated MAPKs (ERK1/2, JNK1/2 and p38MAPK) levels in the neocortex and hippocampus of adult Swiss male mice quantified by western blotting analysis 48 h after the last injection of pentylenetetrazole (PTZ), according to the kindling protocol (35 mg/kg, i.p., on alternated days, with a total of eight injections). The total levels of the investigated MAPKs and the phospho-p38MAPK in the neocortex and hippocampus were not affected by the PTZ injections. The MAPKs phosphorylation levels remain unaltered in PTZ-treated animals without convulsive seizures. The phospho-JNK2 phosphorylation, but not the phospho-JNK1, was increased in the hippocampus of PTZ-treated animals showing 1–3 days with convulsive seizures, whereas no significant changes were observed in those animals with more than 3 days with convulsive seizures. The phospho-ERK1/2 phosphorylation decreased in the neocortex and increased in the hippocampus of animals with 1–4 days with convulsive seizures and became unaltered in mice that showed convulsive seizures for more than 4 days. These findings indicate that resistance to PTZ kindling is associated with unaltered ERK1/2, JNK1/2 and p38MAPK phosphorylation levels in the neocortex and hippocampus. Moreover, when the PTZ kindling-induced epileptogenesis manifests behaviorally, the activation of the different MAPKs sub-families shows a variable and non-linear pattern in the neocortex and hippocampus.

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Abbreviations

PTZ:

Pentylenetetrazole

MAPKs:

Mitogen-activated protein kinases

ERK1/2:

Extracellular signal-regulated kinases 1 and 2

JNK1/2/3:

c-Jun-N-terminal kinases 1-3

p38MAPKa/b/c/d:

p38 Kinases a-d

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Acknowledgments

This study was supported by Grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—Projects: IBN-Net #01.06.0842-00; INCT for Excitotoxicity and Neuroprotection), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Programa de Apoio aos Núcleos de Excelência (PRONEX—Project NENASC), Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC). J.B., P.A.O., F.M.G., T.V.P., A.A.H. and F.C.M. received scholarships from CAPES, CNPq or FAPESC; R.B.L., R.W. and R.D.P. are supported by research fellowships from CNPq-Brazil.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Juliana Ben, Tanara Vieira Peres, Rodrigo Bainy Leal, Roger Walz & Rui Daniel Prediger

  2. Departamento de Farmacologia, Universidade Federal de Santa Catarina, CCB/Bloco D, Florianópolis, SC, 88049-900, Brazil

    Paulo Alexandre de Oliveira, Filipe Carvalho Matheus & Rui Daniel Prediger

  3. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Filipe Marques Gonçalves & Rodrigo Bainy Leal

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

    Alexandre Ademar Hoeller & Roger Walz

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  1. Juliana Ben
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Correspondence to Rui Daniel Prediger.

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Ben, J., de Oliveira, P.A., Gonçalves, F.M. et al. Effects of Pentylenetetrazole Kindling on Mitogen-Activated Protein Kinases Levels in Neocortex and Hippocampus of Mice. Neurochem Res 39, 2492–2500 (2014). https://doi.org/10.1007/s11064-014-1453-5

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