Neuroapoptosis Signaling Pathways in Hippocampus Following Ovariectomy and Its Inhibition by Systemic Estradiol Replacement Therapy

Abstract

In recent decades, there is a growing concern about neurodegenerative diseases (NDs) resulting from the increasing pattern of population age and life expectancy. Although there is no medical treatment for NDs, certain studies have suggested the neuroprotective role of estradiol (ES) in the brain. Hence hormone replacement therapy would be a promising therapeutic alternative for NDs. The present study was performed to investigate the beneficial effect of ES in the neurogenesis and neuro-apoptosis signaling pathways in the hippocampus following ovariectomy (OVX). Thirty Wistar rats were randomly assigned to 5 groups: 1) control 2) OVX, 3) OVX and ES, 4) Surgical sham, and 5) vehicle shams for ES. Eight weeks after surgery, OVX and ES group received an intramuscular injection of ES (20?g/rat) for 30 days, then hippocampi were obtained from all rats for molecular and histology studies. Nissl staining of the hippocampus for neuronal cell counting and western blot for detecting the expression of caspase-3 and cytochrome-c were performed. Based on our findings using western blot, overexpression of apoptotic proteins in the hippocampal tissue was observed in the OVX group. Furthermore, Nissl staining revealed a significant hippocampal neuronal cell death in the OVX group. In a nutshell, ES could result in the increase of neuron cells and the prevention of apoptosis in the hippocampus.