Crocin has a greater therapeutic role in the restoration of behavioral impairments caused by maternal social isolation in adolescent than in adult offspring probably through GSK-3beta downregulation

Abstract

Parental stress drastically impairs cognitive and behavioral functions of the offspring. Social isolation, as one of the most stressful conditions for social animals including rats induces a wide range of destructive effects on behavioral functions. On the other hand, Crocin (active component of Crocus sativa) induces pro-cognitive and neuroprotective effects. In the present study, we aimed to investigate the effects of prolonged maternal social isolation (pre-gestational) and crocin treatment on cognitive and behavioral functions in both adolescent and adult offspring. Female adult rats (mothers) were socially isolated from PND 30 to PND 80 (50 days). The treatment was performed by intraperitoneal injections of crocin (10, 30, and 50 mg/kg) during PND 39–45 or PND 59–65 (7 consecutive days), in the rat offspring. Behavioral assessments were done when the offspring were on PND 45 (adolescent) or PND 65 (adult). The expression level of Glycogen synthase kinase-3 beta (GSK-3beta) in the hippocampus was measured using real-time PCR. The results showed maternal social isolation decreased locomotion and impaired memory in adolescents, and increased anxiety- and depressive-like behaviors and GSK-3beta level, and decreased pain threshold in both adolescents and adults. Crocin (30 and 50 mg/kg) restored or attenuated the effect of maternal social isolation on behavioral functions and GSK-3beta in adolescents and adults, with more effect in adolescents. In conclusion, we showed that crocin treatment can restore the destructive effects of maternal social isolation stress in the offspring, with stronger therapeutic effects in adolescents. Also, GSK-3beta downregulation may underlie the beneficial effects of crocin.