Effects of Exogenous Estrogen Treatment on Hippocampal Neurogenesis of Diabetic Ovariectomized Rats

Background: Mellitus Diabetes (DM) is the most important metabolic diseases. The incidence of DM is prone to increase. Vasculopathy, retinopathy, central and peripheral neuropathy are the most important reported side effects of DM. Cognitive dysfunction following DM reported in both sexes. Hippocampus is a major part of brain involving in cognitive function, its cells are able to neurogenesis, so it is possible that DM affects the hippocampus. In addition, neuroprotective effects of female sex steroids are reported elsewhere. In order to answer the question of whether female sex steroid are able to suppress the effects of DM on neurogenesis of dentate gyrus (DG) in diabetic ovariectomized rat the present study designed.

Methods: Sprague-Dawley adult female rats were used in this study. The animals randomly divided in 8 groups including; control, diabetic (Diab), ovariectomy (OVX), Diab+OVX, estrogen treated (E2; Diab+OVX+E2), surgical and vehicle sham. Intrapritoneal injection of STZ, subcutaneous injection of E2 and routine bilateral surgery were used respectively to induce diabetes, estrogen treatment and OVX. Nissl staining, Brdu immunohistochemistry (IHC) and western blotting were used in this study. Statistical analysis was done and the results presented in mean ± SD, Pv < 0.05 considered significant.

Results: Brdu IHC showed that the neurogenesis significantly decreased in OVX, Diab and OVX-Diab groups (Pv < 0.05) in comparison with control and sham groups. Western blotting showed significant increase of Bax and decrease of Bcl2 proteins of trial groups comparing to control. Estrogen treatment significantly improved neurogenesis in animals of Diab+OVX+E2 group. The neurogenesis impairment was more sever in OVX + Diab animals than OVX and Diab ones merely.

Conclusion: Based on our data, cognitive dysfunction caused by DM is related to hippocampal neurogenesis reduction and might improve under the influence of ovarian steroidal hormone therapy.