Role of microRNA-126 in vascular cognitive impairment in mice

• Published in: Journal of cerebral blood flow and metabolism Vol. 39; no. 12; pp. 2497 - 2511
• Main Authors: Yu, Peng, Venkat, Poornima, Chopp, Michael, Zacharek, Alex, Shen, Yi, Ning, Ruizhuo, Liang, Linlin, Li, Wei, Zhang, Li, Landschoot-Ward, Julie, Jiang, RongCai, Chen, Jieli
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2019
• Subjects: Animals; Cerebrovascular Circulation; Cognitive Dysfunction - genetics; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Dementia, Vascular - genetics; Dementia, Vascular - metabolism; Dementia, Vascular - pathology; Dendritic Spines - metabolism; Dendritic Spines - pathology; Disease Models, Animal; Endothelial Cells - metabolism; Endothelial Cells - pathology; Humans; Male; Mice; Mice, Knockout; Microglia - metabolism; Microglia - pathology; MicroRNAs - biosynthesis; MicroRNAs - genetics; Neuronal Plasticity; Original; Aquaporin 4; white matter; microRNA-126; vascular dementia; cognition disorders
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1177/0271678X18800593

Vascular dementia (VaD) affects cognition and memory. MicroRNA-126 (miR-126) is an angiogenic microRNA that regulates vascular function. In this study, we employ a multiple microinfarction (MMI) model to induce VaD in mice, and investigate VaD-induced cognitive dysfunction, white matter (WM) damage, glymphatic dysfunction and the role of miR-126 in mediating these effects. Male six-to eight-months old C57/BL6 mice (WT) were subject to MMI model, and cerebral blood flow (CBF), vessel patency, glymphatic function, cognitive function, and serum miR-126 expression were measured. Mice were sacrificed at 28 days after MMI. To investigate the role of miR-126 in VaD, cognitive function, water channel integrity and glymphatic function were assessed in male, six-to eight months old conditional-knockout endothelial cell miR-126 (miR-126EC−/−), and control (miR-126fl/fl) mice. MMI in WT mice induces significant cognitive deficits, decreases CBF and vessel patency; evokes astrocytic and microglial activation, increases inflammation, axonal/WM damage; decreases synaptic plasticity and dendritic spine density, instigates water channel and glymphatic dysfunction, and decreases serum miR-126 expression. MiR-126EC−/− mice exhibit significant cognitive impairment, decreased CBF, myelin density and axon density, increased inflammation, and significant water channel and glymphatic dysfunction compared to miR-126fl/fl mice. Reduction of endothelial miR-126 expression may mediate cognitive impairment in MMI-induced VaD.