Neuroprotective Effects of Imipramine Against Memory Impairment and Caspase-3 Cleavage in STZ Induced Alzheimer’s Disease

Dysregulation in the metabolism of sphingolipids has been reported in various diseases, including Alzheimer’s disease (AD). Ceramides areone of the most important bioactive members of this family that an increase in its amount was detected in AD brain. Tricyclic antidepressants (TCAs) are a class of medications which negatively regulate Ceramide levels. So far, there is no study about the effect of these drugs onmemory impairment and apoptosis in STZ-induced AD model. Materials and Methods: In this study, male wistar rats were administrated STZ intracerebroventricularly (icv, day 0 and day 2) and treated with intraperitoneal (ip) injection of imipramine (10 and 20 mg/kg) for 14consecutive days. Then spatial learning and memory were assessed by Morris water maze on days 15-18. After that, the hippocampi of rats were isolated and the amount of the cleaved caspase-3 was analyzed using western blotting. Results: The results showed that whileSTZ administration caused memory impairment, the treatment of animals with imipramine could prevent memory impairment dose-dependently. Furthermore, at the molecular level, imipramine reduced the amount of cleaved caspase-3. Conclusion: Our findings, for thefirst time, showed that imipramine has effects other than previous known effects including memory improvement. Since imipramine can inhibit ceramide synthesis, these results imply that normalized ceramide level might play role in such neuroprotective effects.