Enriched Environment Prevents Cognitive Impairment and Tau hyperphosphorylation after Chronic Cerebral Hypoperfusion

Zhao-hui      Yao; Jun-jian      Zhang; Xiao-feng      Xie

doi:10.2174/156720212801618974

Abstract

Chronic cerebral hypoperfusion (CCH) has been gradually prevalent in the patients over middle age, especially the old over 60 years. It has been proved that CCH is highly related with cognitive impairment. CCH emerges not only in vascular dementia (VaD), but also in Alzheimer’s disease (AD), which regarded as a critical causative for cognitive impairment in these diseases. Nevertheless, the mechanisms underlying cognitive deficit remain elusive. Moreover, there are no dramatically effective preventions. In the present study, by employing a recognized CCH rat model, we found that CCH induced spatial learning/memory deficits with simultaneously increasing tau hyperphosphorylation at multiple Alzheimer-related phosphorylation sites with activation of glycogen synthase kinase-3β (GSK-3β), Cyclin-dependent kinase (Cdk5), Calcium/calmodulin-dependent protein kinase II (CaMKII), and protein kinase B (Akt), and inhibition of protein phosphatase (PP) 2A (PP-2A). Interestingly, enriched environment (EE) treatment, an effect environment stimuli filled with various novel objects, could prevent rats from the EE-induced memory deficits and alterations of tau hyperphosphorylation. Our data suggested that EE might be potentially used for attenuating the detrimental cognition induced by CCH through regulating tau hyperphosphorylation.

Keywords: Chronic cerebral hypoperfusion, enriched environment, tau hyperphosphorylation, Nissl staining, kinase, cerebral blood flow, prodromal, CCH, Amyloid beta , glial activation, N-Methyl-D-aspartate, oligodendrocyte, hyperphosphorylation, dentate gyrus (DG)