ABSTRACT
Mesial temporal lobe epilepsy (MTLE) is associated with severe neuronal death and reactive gliosis in hippocampus. However, the molecular mechanisms underlying these pathological changes remain unanswered. ERK has been reported chronically activated in reactive glia of human epileptic hippocampus. In the present study, we investigated which of the downstream signaling molecules of ERK would be involved in MTLE. Western blot analysis demonstrated that CREB and p90RSK were strongly activated in MTLE patients. Increase in the active forms of CREB and p90RSK resulted not only from the increase in their phosphorylation levels but also from the increase in the protein levels. Activation of CREB and p90RSK was noted in the whole subfields of hippocampus with Ammon's horn sclerosis (AHS) representing a distinctive cellular distribution. However, the common major change was present in proliferating reactive astrocytes. In contrast, their activation was not significant in adjacent temporal lobes despite the presence of a number of astrocytes expressing high levels of GFAP. Our results demonstrate that chronic activation CREB and p90RSK in the epileptic hippocampus may be closely associated with the histopathological changes of AHS.
Subject(s)
Humans , Blotting, Western , Cyclic AMP Response Element-Binding Protein/metabolism , Enzyme Activation , Epilepsy/enzymology , Epilepsy, Temporal Lobe/enzymology , Hippocampus/enzymology , Immunohistochemistry , Mitogen-Activated Protein Kinases/metabolism , Ribosomal Protein S6 Kinases, 90-kDa/metabolism , Signal Transduction , Temporal Lobe/enzymologyABSTRACT
Oitocentos e noventa e quatro epiléticos adultos tratados no período de 1983 a 1992 foram estudados retrospectivamente. Valores anormais de enzimas foram detectados em 49 por cento (n=438) dos casos. Em 200 pacientes (22.3 por cento), ao menos duas dosagens obtidas em momentos diferentes estavam alteradas. Estes últimos foram divididos em 3 grupos: GI, com alteraçoes de transaminases (3 por cento, n=6); GII com alteraçoes de gama-glutamil-tranferase (GGT) e fosfatase alcalina (AP) (72 por cento, n=144) e GIII com alteraçoes nos dois grupos de enzimas (25 por cento, n=50). Nenhum paciente desenvolveu sinais ou sintomas de doença hepática. O aumento de GGT e AP em pacientes em uso de drogras atiepiléticas é frequente e pode nao ter significado patológico. Pequenos aumentos de transaminases também podem ocorrer sem correçao clínica.