title: Amelioratory effects of testosterone treatment on cognitive performance deficits induced by soluble Aβ1-42 oligomers injected into the hippocampus.
abstract: 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.
authors: Department of Human Anatomy, Hebei Medical University, Shijiazhuang, PR China.
authors: Jianxin
authors: J
authors: Jia
authors: Lin
authors: L
authors: Kang
authors: Sha
authors: S
authors: Li
authors: Dandan
authors: D
authors: Geng
authors: Ping
authors: P
authors: Fan
authors: Lei
authors: L
authors: Wang
authors: Huixian
authors: H
authors: Cui
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000009:adverse effects*; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009919:Orchiectomy; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D013739:Testosterone / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D013739:Testosterone
keywords: Androgen receptor; Flutamide; Gonadectomy; Morris water maze; Soluble Aβ1–42 oligomer; Testosterone