OBJECTIVETo investigate the effect of rapamycin, an mTOR inhibitor, on learning and memory ability of mice with pilocarpine (PILO)-induced seizure.

METHODSOne hundred and sixty male adult ICR mice were randomly grouped as vehicle control (n=20), rapamycin control (n=20), PILO model (n=40), rapamycin pre-treatment (n=40) and rapamycin post-treatment (n=40). PILO model and rapamycin treatment groups were injected with PILO to induce temporal lobe seizure. Rapamycin was administrated for 3 days before or after seizure. Morris water maze, Y maze and open field were used for the assessment of learning and memory, and FJB and Timm staining were conducted to detect the neuronal cell death and mossy fiber sprouting, respectively.

RESULTSNo significant cell death was observed in the mice with PILO-induced seizure. The learning and memory were impaired in mice 7 to 10 days after PILO-induced seizure, which was evident by prolongation of avoiding latency (P<0.05), decrease in number of correct reaction (P<0.01) and number of crossing (P<0.05). Treatment with rapamycin both pre-and post- PILO injection reversed seizure-induced cognitive impairment. In addition, rapamycin inhibited the mossy fiber sprouting after seizure (P<0.001).

CONCLUSIONRapamycin improves learning and memory ability in ICR mice after PILO-induced seizure, and its mechanism needs to be further studied.

Animals ; Cell Death ; drug effects ; Disease Models, Animal ; Epilepsy ; chemically induced ; drug therapy ; Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred ICR ; Neurons ; drug effects ; pathology ; Pilocarpine ; toxicity ; Sirolimus ; pharmacology