Chronic Cerebral Hypoperfusion Causes Decrease of O-GlcNAcylation, Hyperphosphorylation of Tau and Behavioral Deficits in Mice

Frontiers in Aging Neuroscience

Jin-hua eGu¹  Chun-ling eDai²  CHENG-XIN eGONG²  Fei eLiu²  Yang eZhao²  Khalid eIqbal²  Qun eLiu³ 

[1] Nantong University Medical School;New York State Institute for Basic Research in Developmental Disabilities;The First Hospital of Jilin University;

关键词: neurodegeneration;    Alzheimer’s disease;    cognitive impairment;    O-GlcNAcylation;    Tau phosphorylation;    chronic cerebral hypoperfusion;   

DOI  :  10.3389/fnagi.2014.00010

来源: DOAJ

【 摘 要 】

Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia (VaD) and is also an etiological factor for Alzheimer's disease (AD). However, how CCH causes cognitive impairment and contributes to Alzheimer’s pathology is poorly understood. Here we produced a mouse model of CCH by unilateral common carotid artery occlusion (UCCAO) and studied the behavioral changes and brain abnormalities in mice 2.5 months after UCCAO. We found that CCH caused significant short-term memory deficits and mild long-term spatial memory impairment, as well as decreased level of protein O-GlcNAcylation, increased level of tau phosphorylation, dysregulated synaptic proteins and insulin signaling, and selective neurodegeneration in the brain. These findings provide mechanistic insight into the effects of CCH on memory and cognition and the likely link between AD and VaD.

【 授权许可】

Unknown