Amelioratory effects of testosterone treatment on cognitive performance deficits induced by soluble Aβ1-42 oligomers injected into the hippocampus

This study was undertaken to investigate the protective effects and potential mechanism of testosterone (T) on cognitive performance in adult male rats given bilateral intrahippocampal injections of beta amyloid 1-42 oligomers (Aβ1-42) combined with gonadectomy (Aβ + GDX). A series of experiments were designed to verify the optimal administration time and dose of T and to explore its potential protective mechanisms on spatial ability in Aβ + GDX rats in the Morris water maze test. Aβ1-42 was injected only once two weeks before testing, while T and the androgen receptor (AR) antagonist flutamide (F) were administered daily beginning 2 days before and throughout the 6 days of testing. The Aβ1-42 injection and GDX individually impaired cognitive performance, and the combination of these treatments was additive, leading to even greater impairment. The serum T level peaked at 48 h after administration. T doses ranging from 0.25 to 1.00 mg corresponding to serum T levels of 4.5-21.35 ng/ml improved the spatial ability. Animals administered 0.75 mg of T corresponding to the serum T level of 15.2 ng/ml had the most significantly improved behavioral performances. However, higher T doses of 1.50 and 2.00 mg resulting in serum T levels of 34.8 and 45 ng/ml, respectively, impaired the behavioral performances. F had no effect on the serum T level and spatial ability, but it blocked the activational effect of T. These findings indicate that the effect of T on behavioral performances is partly mediated through ARs.