Sex influences on hippocampal kindling-induced seizures in middle-aged mice

Epilepsy is a chronic neurological disorder, and its prevalence presents a bimodal distribution with high incidences in children and older adults. The incidence of epilepsy does not generally differ between men and women; however, whether this holds true for new-onset epilepsy in older adults is unclear. While studies in animal models of epilepsy may help explore the biological mechanisms relevant to the influences of sex on epileptogenesis, relatively little information is available regarding sex differences in the genesis of epileptic seizures in middle-aged animals. In this study, we addressed this knowledge gap using a mouse model of extended hippocampal kindling. C57 black mice aged between the ages of 12 and 13 months underwent hippocampal kindling as this age roughly corresponds to middle age in humans (∼50 years). Relative to male mice, female mice showed faster-progressing and more severe evoked seizures, a higher tendency to experience spontaneous seizures in the early stage of extended kindling, less frequent expression of hippocampal interictal spikes, and insignificant decreases in hippocampal theta rhythm. Collectively, these results demonstrated the existence of sex-specific differences in hippocampal kindling-induced seizures and suggested that middle-aged female mice have greater but variable susceptibility to hippocampal kindling-induced epileptogenesis compared with male mice of similar age.