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Updated: Aug 30, 2026
Preparation of Acute Human Hippocampal Slices for Electrophysiological Recordings
Published on: May 7, 2020
Chronic activation of CREB and p90RSK in human epileptic hippocampus
Sun Ah Park1, Tai Seung Kim, Kyeong Sook Choi
1Department of Neurology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, CPO Box 8044, Seoul 120-752, Korea.
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.
Insights
Chronic activation of CREB and p90RSK in the hippocampus is linked to pathological changes in mesial temporal lobe epilepsy (MTLE). These signaling molecules are significantly increased in MTLE patients, particularly in reactive astrocytes.
Area of Science:
- Neuroscience
- Molecular Biology
- Epilepsy Research
Background:
- Mesial temporal lobe epilepsy (MTLE) causes significant neuronal death and reactive gliosis in the hippocampus.
- The precise molecular mechanisms driving these pathological changes in MTLE are not fully understood.
- Extracellular signal-regulated kinase (ERK) pathway activation has been observed in reactive glia within human epileptic hippocampi.
Purpose of the Study:
- To investigate the downstream signaling molecules of ERK involved in the pathogenesis of MTLE.
- To determine the activation status and protein levels of CREB and p90RSK in the epileptic hippocampus of MTLE patients.
Main Methods:
- Western blot analysis was employed to assess the phosphorylation and protein levels of CREB and p90RSK.
- Immunohistochemical analysis was used to examine the cellular distribution of activated CREB and p90RSK in hippocampal subfields and adjacent temporal lobes.
Main Results:
- Western blot analysis revealed strong activation of CREB (cAMP response element-binding protein) and p90RSK (90 kDa ribosomal S6 kinase) in MTLE patients.
- Increased active forms of CREB and p90RSK were due to elevated phosphorylation and protein levels.
- Activation was observed throughout hippocampal subfields, notably in proliferating reactive astrocytes associated with Ammon's horn sclerosis (AHS), but not significantly in adjacent temporal lobes.
Conclusions:
- Chronic activation of CREB and p90RSK in the epileptic hippocampus is closely associated with the histopathological features of AHS in MTLE.
- These findings highlight the potential role of CREB and p90RSK signaling in the molecular pathology of MTLE.
