Abstract DP093: Ablation of miR-219 in oligodendrocyte progenitor cells exacerbates white matter damage and cognitive deficits in vascular dementia

Introduction: Vascular dementia (VaD) induces white matter (WM) damage, however, the molecular mechanisms underlying WM dysfunction and VaD remain unclear. The present study investigated the role of miR-219 in VaD-induced WM damage. Methods: MiR-219 mediates oligodendrocyte progenitor cell (OPC) function. To investigate the potential role of miR-219 in VaD-induced WM damage, we generated an inducible transgenic mouse line with specific ablation of miR-219 in oligodendrocyte progenitor cells (NG2-Cre ERT2 ; miR-219 flox ; Tau/GFP, miR-219 KO). VaD was induced by intracarotid administration of cholesterol crystals to provoke multiple microinfarcts (MMI) in mice. Cognitive and depression-like behaviors were evaluated by the forced swim, Morris water maze, and passive avoidance tests conducted at 21-30 days post MMI. Results: RT-PCR confirmed a significant down regulation of miR-219 in the WM of miR-219 KO mice compared to WT mice. Immunohistochemistry revealed that wild-type MMI mice (WT+MMI) significantly reduced NG2 + OPCs and diminished myelin basic protein (MBP) in the corpus callosum (CC). However, compared to WT-MMI, miR-219 KO MMI mice had significant reduction of NG2 + OPCs and MBP + myelin (p