Androgen deprivation can be achieved through testosterone antagonists (chemical castration) with or without orchidectomy. There is this hypothesis that stipulates that testesterone exerts supreme effects on synaptic plasticity, however low testosterone has been linked to type- 2 diabetics mellitus, insulin resistance and Alzheimer’s disease. The aim of the study was to investigate the cellular changes that occur from bilateral orchidectomy and examine the effects of androgen deprivation, orchidectomy and flutamide administration on the histoarchitectural organization of the hippocampus in male Wistar rats.
Thirty-six (36) adult male Wistar rats were randomly divided into into six (6) groups: Control group (distilled water),orchidectomy group (bilateral orchidectomy), flutamide group (oral 10mg,20mg), orchidectomy+flutamide. Animals were sacrificed at 30 days respectively.
The total plasma; testesterone, 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 and lead 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.
Histopathological results showed that flutamide significantly restored the histological damage of rat brain in flutamide treatment+ orchidectomy.