Role of testosterone in memory impairment of Alzheimer disease induced by Streptozotocin in male rats

Background and purpose of the study: Recent studies demonstrate that androgens, beyond regulating sexual behavior, exert several neuroprotective functions in the brain. The present study was designed to explore effect of testosterone in memory impairment induced by intra-cerebroventricular (icv) injection of streptozotocin (STZ) as a model of sporadic AD. Methods: Study was carried out on male Wistar rats. Animals were randomly divided into 11 equal groups. Experimental model of AD was induced by bilateral icv injection of STZ at the dose of 750 mu g/Rat/10 mu l ACSF at days 1 and 3. STZ-induced memory impairment was assessed two weeks after the last dose of STZ by using a passive avoidance task (1 mA). The interval between the placement of animals in the illuminated chamber and the entry into the dark chamber was measured as a step-through latency (STL). Castration was performed by surgical removing of testis and behavioral study of memory impairment was done after 4 weeks. Results: Results of this study showed that icv injection of STZ could induce marked (p < 0.05) memory impairment at the dose of 750 mu g/Rat/dissolve 10 mu l CSF/bilateral/days 1 and 3. Therefore, we used this dose of STZ for induction of experimental model of AD. Memory was worsened in castrated rats (P < 0.05) when compared with normal and sham-operated animals. Testosterone replacement therapy (1 mg/kg, sc, for 6 days) in 4 week castrated rats restored memory up to the level of control groups. Testosterone had not any significant effect on memory impairments of non-castrated rats. Major conclusion: According to the obtained results it can be concluded that testosterone improves cognitive and memory impairment of AD. We suggest that testosterone replacement therapy may have beneficial effect in ameliorating memory impairments of senile patients suffering from AD. Further clinical studies should be carried out to prove possible useful effect of testosterone as an adjuvant therapy in AD.