Effects of exogenous melatonin on Bax and P53 expression in substantia nigra of adult rat menopause model following pinealectomy

Abstract

Background: Melatonin which also called “dark hormone” is released from the pineal gland and is well known for its role in regulating biological rhythms in all mammals. Recently more other functions have been reported for melatonin. Among these roles, its function as an antioxidant is more emphasized by researchers. Recent findings also have showed reciprocal interaction between gonadal hormones and nervous system. Gonadal hormones have dramatic genomic and non-genomic effects on certain structures of the brain. Substantia nigra (SN) which is the main source of dopaminergic outputs is influenced by female sex hormones; it has also intercellular receptors for melatonin. In order to find the co-effects of exogenous melatonin and gonadal steroid deprivation on SN the present research was done. Material and methods: Fifty adult female Sprague-Dawley rats were used in this study. The animals randomizely divided into groups including pinealectomized (PX), ovariectomized (OVX) with and without exogenous melatonin, PX+ OVX with and without exogenous melatonin, sham and control groups were also considered. Pinealectomy was done after 4 weeks of ovariectomy. Three weeks after pinealectomy the animals received 20 mg/kg melatonin for 60 days. On day 60 the animals perfused and fixed, their brain removed and prepared for TUNEL staining. By using western blotting, Bax and P53 protein expression in SN was assayed. Results: Our findings with TUNEL staining showed the number of apoptotic nuclei of the animals which treated by injection of melatonin 20 mg/kg after 10 days was significantly less than the PX, OVX and PX+OVX groups (p< 0.001). The western blotting analysis showed that the expression of Bax proapoptotic protein in OVX + mel, PX+ mel and OVX+PX+ mel showed significant decrease compared with PX, OVX and PX+OVX groups. We found the same results for expression of P53. Conclusion: Based on our findings the role of melatonin as an antioxidant to prevent cell loss was confirmed. In addition; it seems that there is no dominancy in cell death preventing between exogenous melatonin and female gonadal steroids.