Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Brain Pathology

DOI: 10.1111/bpa.70045