Environmental Enrichment Influences BDNF and NR1 Levels in the Hippocampus and Restores Cognitive Impairment in Chronic Cerebral Hypoperfused Rats

Huimin      Sun; Junjian      Zhang; Lei      Zhang; Hui      Liu; Hong      Zhu; Ying      Yang

Abstract

An enriched environment (EE) is beneficial in modifying behaviors, particularly in tasks involving complex cognitive functions. However, the impact of EE on cognitive impairment induced by chronic cerebral hypoperfusion (CCH) has not been studied. We investigated the effects of EE on cognitive impairment caused by CCH and examined whether CCH altered the protein levels of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR1) and subunit 2B (NR2B) in the hippocampus of rats and whether EE exposure attenuated the effects. Rats were divided into four groups that received either permanent bilateral ligation of the common carotid arteries (2-vessel occlusion) surgery or sham surgery followed by either EE housing or standard environment housing for 4 weeks. We examined non-spatial recognition memory in the novel object recognition task, spatial learning, and memory ability in the Morris water maze as well as the protein levels of BDNF, NR1, and NR2B in the hippocampus. CCH impaired both spatial and non-spatial cognitive functions, and EE exposure reversed the spatial cognitive performance and improved non-spatial memory performance. CCH resulted in decreased levels of BDNF and NR1 protein in the hippocampus, and EE exposure restored the decreased expression. Our results demonstrate for the first time that EE exposure restores cognitive impairment induced by CCH and up-regulates the decreased protein levels of BDNF and NR1. Inversely, BDNF and NR1 may contribute to the beneficial effects of EE on CCH in rats.

Keywords: Brain-derived neurotrophic factor, chronic cerebral hypoperfusion, enriched environment, N-methyl-D-aspartate receptor, non-spatial memory, spatial memory, NR1, Hippocampus, NR2B, ANOVA, NE, PBS, SE, Morris Water Maze, IOD, Dunnett's post-test, β-actin bands, western blotting, 2-VO, Alzheimer's disease, LTP, CA1 region, mRNA, protein expression, dementia