Characterization of Hippocampal Synaptic Plasticity in Orchidectomized Insulin-Resistant Rats

Abstract

Background Androgen deprivation could be created through testosterone antagonists (castration using chemicals) with or without orchidectomy. There is this hypothesis that stipulates that testosterone may have supreme effects on synaptic plasticity, and in the recent past low testosterone has been linked to type-2 diabetics, insulin resistance and Alzheimer’s disease. The present study investigated the cellular changes that occur from bilateral orchidectomy and examined the effects of androgen deprivation, orchidectomy and flutamide administration on the histoarchitectural organization of the hippocampus in male Wistar rats. Methodology This purpose, thirty-six(36) presumably healthy male rats were randomly divided into six groups, A, B, C, D, E, F and treatment lasted for 30 days in the various groups as follows; n-6, Group A = Control; Group B = Orchidectomy only; Group C = Flutamide (10mg/kg); Group D = Flutamide (20mg/kg); Group E = Orchidectomy + Flutamide (10mg/kg); Group F = Orchidectomy + Flutamide (20mg/kg). Tissues processed for histology, histochemistry and biochemical parameters. Results The total plasma; testosterone, insulin levels, fasting blood glucose, and nitric oxide were assayed; the homeostasis model for insulin resistance was also calculated. Histological examinations by Hematoxylin and Eosin(H&E) and Cresyl fast violet (CFV), while immunohistochemical analysis of astrocytes were performed using Glial fibrillary acidic protein (GFAP). Results of study show that androgen deprived insulin-resistance state primarily affects fasting blood glucose leading to increases in the level of serum insulin, glucose and nitric oxide and caused a decrease in serum testosterone levels. The hippocampal response to flutamide was unaffected by blockade of intracerebral estrogen biosynthesis. In comparison flutamide alone increased CA1 spine synapse density also whereas in combination the effects of flutamide + orchidectomy were additive rather than inhibitory. Conclusion Histopathological results showed that flutamide significantly restored the histological damage of rat brain in flutamide treatment + orchidectomy.