Impairment of Spatial Working Memory but Preservation of Recognition Memory in Female Rats with Spontaneous Absence Seizures

Epidemiological studies reveal gender-specific differences in epilepsy. Childhood absence epilepsy (CAE), which is more prevalent in females, is characterized by typical absence seizures (ASs) consisting of brief periods of unconsciousness, associated with 2.5–4 Hz spike-wave discharges (SWDs) in the electroencephalogram (EEG). Children with CAE often present neuropsychological comorbidities, including deficits in attention and executive function. In this study, we investigated anxiety-like behaviour and memory in female Genetic Absence Epilepsy Rat from Strasbourg (GAERS), a validated model of ASs, compared to Non-Epileptic Control (NEC) and Wistar rats. We found that female GAERS generally showed normal anxiety-like behaviour relative to both control strains, although some tests suggested a reduction in anxiety. Importantly, female GAERS showed impaired spatial working memory, while recognition memory was preserved. These findings when compared with previous data in males indicate that while anxiety levels in female GAERS are preserved as those of male GAERS, memory performance differs, with males showing impairments in both spatial working memory and recognition memory. These findings emphasize the importance of considering gender differences in both clinical and preclinical epilepsy research to better understand the neuropsychological comorbidities associates with ASs. This knowledge is crucial for the identification of gender-specific mechanism, as well as the development of gender-sensitive, personalized therapies targeting both seizures and associated cognitive impairments.