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

Background: the potential neuroprotective role of estradiol in neurodegenerative diseases (nds), suggests the role of hormone replacement therapy (hrt) in nds. the present study investigated the possible beneficial implications of the exogenous β estradiol (es) in the neuro-apoptosis signaling pathways in the hippocampus following long-term ovariectomy (ovx).materials and methods: thirty wistar adult female rats were randomly assigned to 5 identical groups (n=6): 1-control (intact rats), 2-ovx (ovariectomized rats), 3-ovx+estradiol (eight weeks after ovariectomy, then intramuscular injection of 20μg/rat β estradiol for 30 days), 4-surgical sham (underwent only surgical incision), and 5-vehicle sham (eight weeks after ovariectomy, received sesame oil for 30 days). three months following the assignment (two months post-ovx plus one month of estradiol injection for the intervention group), animals were perfused, and the hippocampus was obtained from all rats for molecular and histological studies. nissl staining for neuronal cell counting and western blot for expression of cleaved caspase-3 and cytochrome-c were performed.results: hippocampal neural density decreased in the ovx group (p<0.01 compared to the control), while it was restored in the ovx+es group (p<0.01 compared to both ovx and sham vehicle groups). furthermore, the cytochrome-c and cleaved caspase-3 expression increased in the ovx group in comparison to the control (p<0.01), whereas that of the ovx+es decreased compared to the ovx group (p<0.01). in conclusion, diminished hippocampal neural density and overexpression of apoptotic proteins were observed in the ovx group.conclusion: estradiol could preclude neural loss and reduce apoptotic protein expression, providing an important estrogen-induced neuroprotection mechanism via the apoptosis signaling pathway inhibition, this needs to be confirmed in further studies.