The Estrogen-mediated Antidepressant-like Effect Of Betaine

Betaine is widely expressed in plants and animals,and reported to have many pharmacological activities,including anti-epileptic,anti-fatty liver and anti-tumor effects.However,the estrogen-mediated antidepressant effect of betaine has not been well clarified.Therefore,the present study was aimed to investigate the estrogen-mediated antidepressant-like of betaine on ovariectomized mice as a perimenopausal depression model,and combining use of behavioral pharmacology,immunohistochemistry and Western blot to investigate the mechanism about antidepressant-like effect of betaine.The results showed that immobility time was significantly shortened by betaine（30.0 mg/kg,i.p）in forced swim test（FST）,and this effect was inhibited by injection of 5-HT₂ receptor antagonist Ketanserin（Ket,5.0 mg/kg,i.p）.Immunohistochemistry was used to examine c-Fos induction by betaine.Our data showed that c-Fos expression level was significantly reduced after ovariectomy,and intraperitoneal injection with a concentration of 30.0 mg/kg betaine significantly upregulated c-Fos expression in the hippocampus and prefrontal cortex parts.Furthermore,this effect of betaine on c-Fos was also blocked by Ket.Western blot results showed that: betaine enhanced prefrontal cortex STAT₃,CREB and BDNF expression levels.Taken together,betaine produces a significant improvement in ovariectomized mice which exhibit depressive–like responses in ovariectomized mice,which may be related to activation of 5-HT₂ receptors by enhancing the hippocampus and prefrontal cortex neuronal activity.This will be helpful to develop a potential drug for depression.