Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice

Together with pharmacoresistant seizures, the quality of life of temporal lobe epilepsy (TLE) patients is negatively impacted by behavioral comorbidities including but not limited to depression, anxiety and cognitive deficits. The pilocarpine model of TLE has been widely used to study characteristics of human TLE, including behavioral comorbidities. Since the outcomes of pilocarpine-induced TLE might vary depending on several experimental factors, we sought to investigate potential gender-related differences regarding selected behavioral alterations in C57BL6 mice. We found that epileptic mice, independent of gender, displayed increased anxiety-like behavior in the open-field test. In the object recognition test, epileptic mice, regardless of gender, showed a decreased recognition index at 24 (but not at 4) hours after training. On the other hand, no significant differences were found regarding mice learning and memory performance in the Barnes maze paradigm. Motor coordination and balance as assessed by the beam walk and rotarod tests were not impaired in epileptic mice of both genders. However, female mice, independent of epilepsy, performed the beam walk and rotarod tasks better than their male counterparts. We also found that only male epileptic mice displayed disturbed behavior in the forced swim test, but the mice of both genders displayed anhedonia-like behavior in the taste preference test. Lastly, we found that the extent of hilar cell loss is similar in both genders. In summary, both genders can be successfully employed to study behavioral comorbidities of TLE; however, taking the potential gender differences into account may help choose the more appropriated gender for a given task, which may be of value for the minimization of the number of animals used during the experiments.