Hippocampal cellular changes in androgen deprived insulin resistant rats.

Abstract

Androgen deprivation can be achieved through testosterone antagonists (chemical castration) with or without orchidectomy. We use a rat model to characterize hippocampal structural and functional changes that might be associated with a subset population of androgen deprived insulin-resistant patients. Adult male Wistar rats assigned into six (6) groups: control group (distilled water/sham), orchiectomy group (bilateral orchiectomy), flutamide group (oral flutamide; 11mg/kg body weight), diabetes group (multiple low-dose of streptozotocin (STZ; 30mg/kg body weight intraperitoneally), orchiectomy and diabetic group (bilateral orchiectomy with 30mg/kg body weight of STZ), and orchiectomy/diabetic/flutamide group (bilateral orchiectomy with 30mg/kg body weight of STZ with 11mg/kg body weight of flutamide). Animals were sacrificed at 30 and 60days respectively. Spatial learning and working memory behavior were assessed; while total plasma; testosterone, insulin levels, and fasting blood glucose were assayed; the Homeostasis model for insulin resistance was also calculated. Histological examinations by H&E and CFV, while immunohistochemical analysis of astrocytes, P53 protein, and NSE were performed. Androgen deprived insulin-resistant state caused altered learning and cognitive behavior through decreased percentage correct alternation to an increased escape latency period. Significant bidirectional correlates exist between the hormonal profiles relative to the control group (p < 0.05), especially in the 60days post-orchiectomy. While histological and immunohistochemical data indicate microcellular derangement. That the summate effects of androgen deprivation and impaired insulin signaling exacerbate hippocampal neurodegenerative changes that merit further studies.