Abstract
OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is generally associated with cognitive and psychiatric comorbidities. Here we examined whether similar comorbidities are observed in mice injected with kainate in the dorsal hippocampus, a model known to recapitulate many features of human MTLE, and if these comorbidities are sex dependent. METHODS: Male and female C57BL/6 mice were unilaterally injected with kainate in the dorsal hippocampus (KA-MTLE), and hippocampal paroxysmal discharges were recorded over 2 months. Behavioral tests assessed food intake (Novelty Palatable Food Intake test), well-being (Nesting), impulsivity (Marbles test), depression-related behavior (Splash test), spatial learning and memory (Barnes maze), working memory (Y-maze), motor coordination (Climbing Cage test), locomotion and activity (Open Field), and anxiety-like behavior (Elevated Plus Maze). Body weight and estrous cycle were also monitored and compared to saline-injected mice (sham). RESULTS: We observed reduced environmental care (Nesting) but no changes in self-care (Splash test) or impulsivity (Marbles test) in KA-MTLE mice. Spatial memory (Barnes maze) was unaffected, although less efficient strategies were used by these mice. Working memory (Y-maze) remained similar to that of shams. No motor impairments were observed (Climbing Cage test, Open Field), but KA-MTLE mice displayed increased activity without anxiety-like behavior. They gained more weight, while their palatable food intake did not differ from shams, and females showed longer estrous cycles. Death that might correspond to sudden unexpected death in epilepsy (SUDEP) occurred in 10% and 3% of epileptic male and female mice, respectively, vs 0% in shams. SIGNIFICANCE: Our results suggest that KA-MTLE mice display several features (hyperactivity, reduced well-being, subtle cognitive changes) evocative of an attention disorder associated with hyperactivity (attention-deficit/hyperactivity disorder [ADHD]), often described in young patients with MTLE. Along with the increase in body weight and the occurrence of SUDEP, our data further validate this mouse model to study the physiopathology of MTLE and develop treatments for both seizures and associated comorbidities.