Journal Article

Calponin‐3 is associated with epilepsy through the regulation of astrocyte activity

Yang, Meng‐Shi, Chen, Li‐Ling, Yang, Wen‐Qian, Wang, Dan, Wang, Ke, Zhou, Qi‐Xin, Yu, Yan‐Ying, Wu, Qian, Han, Yan‐Bing, Chen, Lu, Gou, Cheng, Xu, Ting‐Wan, Yang, Fei

2026

Overview

Astrocytes contribute in critical ways to the pathophysiology of epilepsy not only through trophic support but also through the regulation of neuronal excitability by modulating glutamate, γ‐aminobutyric acid (GABA), adenosine triphosphate (ATP), and adenosine levels. Calponin‐3 is an actin‐binding protein that is enriched in the brain. We have previously reported that increased calponin‐3 expression is correlated with epileptic seizures. In the present study, we revealed that in the hippocampus of epileptic mice models, increased calponin‐3 protein expression was correlated with the expression of the astrocytic marker glial fibrillary acidic protein (GFAP). Calponin‐3 overexpression in the hippocampus significantly increased susceptibility to epileptic seizures, whereas calponin‐3 downregulation was associated with reduced spontaneous recurrent seizures in mice. Furthermore, changes in calponin‐3 levels corresponded to astrocyte activation in both mice and cultured human astrocytes and were associated with changes in the protein levels of adenosine kinase (ADK) and equilibrative nucleoside transporter 1 (ENT1), which are two key regulators of adenosine metabolism that have been shown to play critical roles in epileptogenesis. Collectively, our findings suggest that calponin‐3 may regulate astrocyte‐mediated adenosine metabolism and could represent a potential therapeutic target for epilepsy. Increased calponin‐3 expression correlates with astrocyte activation in epileptic mice, modulating adenosine metabolism regulators ADK and ENT1. Calponin‐3 overexpression increased susceptibility to epileptic seizures, while its downregulation reduces spontaneous recurrent seizures, identifying it as a potential therapeutic target for epilepsy.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Actin / Adenosine / Adenosine kinase / adenosine kinase (ADK) / Adenosine Kinase - metabolism / Adenosine triphosphate / Animal models / Animals / astrocyte / Astrocytes / Astrocytes - metabolism / Calcium-Binding Proteins - metabolism / Calponin / Calponins / calponin‐3 / Cells, Cultured / Convulsions & seizures / Disease Models, Animal / Epilepsy / Epilepsy - metabolism / Epilepsy - pathology / equilibrative nucleoside transporter 1 (ENT1) / Excitability / Glial fibrillary acidic protein / Glial Fibrillary Acidic Protein - metabolism / Hippocampus / Hippocampus - metabolism / Hippocampus - pathology / Humans / Kinases / Male / Metabolism / Mice / Mice, Inbred C57BL / Microfilament Proteins - genetics / Microfilament Proteins - metabolism / Nucleoside transporter / Proteins / Seizures / Therapeutic targets / γ-Aminobutyric acid