Chronic activation of CREB and p90RSK in human epileptic hippocampus.

Sun Ah Park,Kyeong Sook Choi,Tai Seung Kim,Byung In Lee,Hyun Jin Park,Kyoung Heo

doi:10.1038/emm.2003.48

Sun Ah Park, Kyeong Sook Choi + Show 4 more

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https://doi.org/10.1038/emm.2003.48

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Journal: Experimental and Molecular Medicine	Publication Date: Oct 1, 2003
Citations: 24	License type: cc-by

Affiliation: Yonsei University

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.

Highlights

Mesial temporal lobe epilepsy (MTLE) is the most common partial epilepsy, which is frequently resistant to antiepileptic drug therapy
Ammon's horn sclerosis (AHS) is the most common pathological substrate for drug-resistant MTLE, which is characterized by the histopathological changes of hippocampus consisting of neuronal cell death, enhanced neurogenesis, axonal sprouting, and reactive gliosis (Babb and Brown, 1987)
Among the possible downstream targets Elk, c-AMP response element binding protein (CREB), and p90RSK were specially evaluated in this study because they have been previously reported to play a critical role in hippocampus as a downstream of extracellular signalregulated kinase (ERK) in relation to neuronal excitation (Xia, et al, 1996; Angenstein, et al, 1998; Atkins, et al, 1998)

Summary

Introduction

Mesial temporal lobe epilepsy (MTLE) is the most common partial epilepsy, which is frequently resistant to antiepileptic drug therapy. Ammon's horn sclerosis (AHS) is the most common pathological substrate for drug-resistant MTLE, which is characterized by the histopathological changes of hippocampus consisting of neuronal cell death, enhanced neurogenesis, axonal sprouting, and reactive gliosis (Babb and Brown, 1987). Among the possible downstream targets Elk, c-AMP response element binding protein (CREB), and p90RSK were specially evaluated in this study because they have been previously reported to play a critical role in hippocampus as a downstream of ERK in relation to neuronal excitation (Xia, et al, 1996; Angenstein, et al, 1998; Atkins, et al, 1998). We demonstrate here that cyclic AMP regulatory element binding protein (CREB) and 90-kDa ribosomal S6 kinase (p90RSK) are actively expressed in epileptic hippocampus.

Materials and Methods

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