MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion

• DOI: 10.1038/cddis.2017.243
• Publication Date: 2017-06-01T12:43:09Z
• Authors: Xin Chen; Xue-Mei Jiang; Lin-Jing Zhao; Lin-Lin Sun; Mei-Ling Yan; You Tian; Shuai Zhang; Ming-Jing Duan; Hong-Mei Zhao; Wen-Rui Li; Yang-Yang Hao; Li-Bo Wang; Qiao-Jie Xiong; Jing Ai
• Keywords: Cerebral Cortex; Male; Neurons; 0301 basic medicine; Binding Sites; Base Sequence; Caspase 6; Cell Death; Caspase 3; Primary Cell Culture; Brain Ischemia; Rats; Amyloid beta-Protein Precursor; Cerebrovascular Disorders; MicroRNAs; 03 medical and health sciences; Carotid Arteries; Gene Expression Regulation; Dentate Gyrus; Animals; Original Article; CA1 Region, Hippocampal; Oligoribonucleotides, Antisense

Abstract Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer’s disease vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers crossings dendrites caused death in rat hippocampi cortices. It also led to increase N-terminal β -amyloid precursor protein (N-APP) receptor-6 (DR6) levels activation caspase-3 caspase-6. Further study showed DR6 was downregulated miR-195 overexpression, upregulated inhibition, unchanged binding-site mutation miR-masks. Knockdown endogenous lentiviral vector-mediated overexpression its antisense molecule (lenti-pre-AMO- ) death, N-APP levels, elevated cleaved caspase-6 levels. Overexpression using lenti-pre- prevented these changes triggered 2VO. We conclude is involved CBH-induced dendritic degeneration through N-APP/DR6/caspase pathway.