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

• DOI: 10.1007/s11064-014-1453-5
• Publication Date: 2014-10-14T14:52:19Z
• Authors: Juliana Ben; Paulo Alexandre d...; Filipe Marques Go...; Tanara Vieira Peres; Filipe Carvalho M...; Alexandre Ademar ...; Rodrigo Bainy Leal; Roger Walz; Rui Daniel Prediger
• Keywords: Male; 0301 basic medicine; Mice; 03 medical and health sciences; Kindling, Neurologic; Animals; Pentylenetetrazole; Neocortex; Mitogen-Activated Protein Kinases; Hippocampus

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 p38(MAPK)) 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-p38(MAPK) 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 p38(MAPK) 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.