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Neurochem Res (2014) 39:24922500 DOI 10.1007/s11064-014-1453-5
ORIGINAL PAPER
Effects of Pentylenetetrazole Kindling on Mitogen-Activated Protein Kinases Levels in Neocortex and Hippocampus of Mice
Juliana Ben Paulo Alexandre de Oliveira Filipe Marques Gonalves
Tanara Vieira Peres Filipe Carvalho Matheus Alexandre Ademar Hoeller
Rodrigo Bainy Leal Roger Walz Rui Daniel Prediger
Received: 22 August 2014 / Revised: 7 October 2014 / Accepted: 7 October 2014 / Published online: 15 October 2014 Springer Science+Business Media New York 2014
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 quantied 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 13 days with convulsive seizures, whereas no
signicant 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 14 days with convulsive seizures and became unaltered in mice that showed convulsive seizures for more than 4 days. These ndings 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.
Keywords Epilepsy Kindling Pentylenetetrazole
Mitogen-activated protein kinases (MAPKs)
Hippocampus Neocortex
AbbreviationsPTZ PentylenetetrazoleMAPKs Mitogen-activated protein kinases ERK1/2 Extracellular signal-regulated kinases 1 and 2JNK1/2/3 c-Jun-N-terminal kinases 1-3 p38MAPKa/b/
c/d
p38 Kinases a-d
Introduction
Epilepsies are characterized by recurrent spontaneous seizures due to abnormal hyper synchronic neuronal hyper-activity in the brain [13]. Clinical treatment with antiepileptic drugs enhance...