title: Enriched environment prevents cognitive impairment and tau hyperphosphorylation after chronic cerebral hypoperfusion.
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.
authors.affiliation: Department of Neurology, Zhongnan hospital, Medical Center of Wuhan University, 169 Donghu Road, Wuhan, PR China.
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Yao
authors.forename: Jun-jian
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Xie
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D054059:Coronary Occlusion / Q000150:complications; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D004195:Disease Models, Animal; D004777:Environment; D005786:Gene Expression Regulation / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000209:etiology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D010744:Phosphoric Monoester Hydrolases