Connexin43 and Astrocyte Uncoupling in Epilepsy

During my doctoral and early postdoctoral work, I studied how astrocyte network dysfunction contributes to temporal lobe epilepsy. I investigated astrocytic gap-junction coupling, connexin43 localization, phosphorylation, protein remodeling and astrocyte survival using human epilepsy tissue, mouse models, high-resolution microscopy, protein biochemistry, proteomics and quantitative image analysis.

The mechanistic correction

My first-author work showed that astrocyte uncoupling in epilepsy is not simply caused by loss of connexin43 protein. Instead, connexin43 is increased overall but redistributed toward perivascular endfeet, and shows altered C-terminal phosphorylation at sites relevant to channel permeability — linking astrocyte network failure to post-translational regulation, blood-brain barrier dysfunction and seizure-associated tissue remodeling.

I later showed that deletion of astrocytic connexins aggravates chronic seizure and interictal spike activity, supporting the idea that intact astrocyte coupling is functionally protective during epileptogenesis.

Why it still matters

This is the mechanistic foundation for the RNA-editing concept in my research vision: if seizure-associated phosphorylation at connexin43 S255/S368 is what breaks coupling, then recoding those serines is a way to test the mechanism — and potentially to intervene.