Sigma-1 Expression in Chronic Mouse Models of Temporal Lobe Epilepsy

Sigma-1 is an atypical receptor protein that modulates neuronal excitability and cellular stress responses, making it a promising target for therapeutic epilepsy management. However, its expression profile following epileptogenic insults, during epileptogenesis, and following chronic epilepsy manifestation remains unclear. We investigated brain Sigma-1 expression immunohistochemically and via quantitative PCR in two chronic mouse models of temporal lobe epilepsy: the amygdala kindling and intrahippocampal kainate model. Thereby, different disease phases were considered from the early phase following an epileptogenic insult, epileptogenesis, to the chronic epileptic state with recurrent seizures. Sigma-1 expression was largely stable across the examined brain areas. Transient increases in expression intensity were observed 2 days after status epilepticus in the kainate model in the CA3 region of the hippocampus and the entorhinal cortex, whereas no persistent protein-level reductions were detected in the chronic phase. Descriptive coexpression analyses indicated Sigma-1 expression in excitatory and inhibitory neurons, astrocytes, and microglia. These findings indicate that Sigma-1 expression is preserved during epileptogenesis and chronic epilepsy, supporting the continued consideration of Sigma-1 as a potential therapeutic target in epilepsy management. The early alterations observed following an epileptogenic insult further support the rationale for investigating Sigma-1-directed interventions during epileptogenesis, including preventive antiepileptogenic approaches.