Persistent increased DNA-binding and expression of serum response factor occur with epilepsy-associated long-term...

Area of Science:

• Neuroscience
• Molecular Biology
• Epilepsy Research

Background:

• NMDA receptor activation during status epilepticus (SE) is crucial for epilepsy development.
• Epilepsy in models and humans is permanent, suggesting lasting brain plasticity changes.
• NMDA receptor activation transiently affects the transcription factor serum response factor (SRF).

Purpose of the Study:

• To investigate long-term alterations in SRF expression and DNA binding after SE in the pilocarpine epilepsy model.
• To determine if NMDA receptor activation during SE is responsible for persistent SRF changes.
• To understand the role of SRF in the long-lasting plasticity associated with epileptogenesis.

Main Methods:

• Utilized the pilocarpine model of epilepsy in rats.
• Analyzed hippocampal and cortical nuclear extracts for SRF DNA binding and SRF protein levels.
• Employed immunohistochemistry to localize SRF expression in the hippocampus.
• Investigated the necessity of NMDA receptor activation during SE for SRF alterations.

Main Results:

• SRF DNA binding and protein levels were significantly increased in hippocampal extracts 24 hours and 8 weeks post-SE.
• Persistent increase in SRF DNA binding was observed in cortical but not cerebellar extracts.
• Hippocampal SRF expression was localized to neurons.
• NMDA receptor activation during SE was essential for these persistent SRF changes.

Conclusions:

• Serum response factor (SRF) is persistently elevated in the hippocampus and cortex after status epilepticus (SE).
• These long-term changes in SRF are initiated by NMDA receptor activation during SE.
• Elevated SRF contributes to the long-lasting gene expression and plasticity changes underlying epileptogenesis.