Effect of bexarotene on spatial cognition, impairment in memory and learning and hippocampal nerve regeneration of Aβ25-35 mice

Abstract

Objective To explore the effect of bexarotene (BEX) on spatial cognition,impairment in memory and learning and hippocampal nerve regeneration of Aβ25-35 mice.Methods Eighty healthy male ICR mice were randomly divided into control group,model group,low-dosage BEX treatment group and high-dosage BEX treatment group (n=20); AD mouse models in the later three groups were induced by intracerebroventricular injection of Aβ25-35; and mice in the low-dosage BEX treatment group and high-dosage BEX treatment group treated with BEX (50 and 100 mg/kg·d) by gavage 7 days after Aβ25-35 injection for consecutive 14 days.Morris water maze and Y-maze tests were used to test the spatial cognitive function and abilities of learning and memory,respectively,28 days after Aβ25-35 injection.Intraperitoneal injection of 5-bromodeoxyuridine (BrdU) three times daily for 28 days was performed,and then,immumohistochemical staining was employed to detect the BrdU expression in the hippocampus; dual cortex protein (DCX) staining and Hoechst staining were,respectively,used to evaluate the proliferation and migration,and apoptosis of neuronal precursor cells; toluidine blue staining was employed to evaluate the mature neurons in the hippocampus.The levels of hippocampal brain-derived neurotrophic factor (BDNF) and the expressions of hippocampal glial fibrillary acidic protein (GFAP) and growth associated protein-43 (GAP-43) were measured by ELISA and Western blotting,respectively.Results Morris water maze test showed that the latency of crossing the platform was gradually increased in the control group,high-dosage BEX treatment group,low-dosage BEX treatment group and model group on the 3nd,4th,5th and 6th day,and the duration of stay was gradually decreased on the 6th day; increased learning frequency and reduced memory frequency was noted in Y-maze test; number of BrdU-positive cells,length and density of DCX neurite,and number of granule cells in the hippocampus decreased gradually,while Hoechst-positive cells decreased gradually; hippocampal levels of GFAP,GAP-43 and BDNF decreased gradually; the differences in the above levels were statistically significant (P＜0.05).Conclusion BEX can improve the spatial cognition and the impairment in memory and learning and promote their hippocampal neurogenesis of Aβ25-35 mice. Key words: Bexarotene; Aβ; Spatial cognition; Impairment in memory and learning; Hippocampal neurogenesis