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BackgroundNeural precursor cell (NPC) migration toward lesions is key for neurological functional recovery. The neovasculature plays an important role in guiding NPC migration. MicroRNA‐210 (miR‐210) promotes angiogenesis and neurogenesis in the subventricular zone and hippocampus after cerebral ischemia; however, whether miR‐210 regulates NPC migration and the underlying mechanism is still unclear. This study investigated the role of miR‐210 in NPC migration.Methods and ResultsNeovascularization and NPC accumulation was detected around ischemic foci in a mouse model of middle cerebral artery occlusion (MCAO) and reperfusion. Bone marrow–derived endothelial progenitor cells (EPCs) were found to participate in neovascularization. miR‐210 was markedly upregulated after focal cerebral ischemia/reperfusion. Overexpressed miR‐210 enhanced neovascularization and NPC accumulation around the ischemic lesion and vice versa, strongly suggesting that miR‐210 might be involved in neovascularization and NPC accumulation after focal cerebral ischemia/reperfusion. In vitro experiments were conducted to explore the underlying mechanism. The transwell assay showed that EPCs facilitated NPC migration, which was further promoted by miR‐210 overexpression in EPCs. In addition, miR‐210 facilitated VEGF‐C (vascular endothelial growth factor C) expression both in vitro and in vivo. Moreover, the luciferase reporter assay demonstrated that miR‐210 directly targeted the 3′ untranslated region of SOCS1 (suppressor of cytokine signaling 1), and miR‐210 overexpression in HEK293 cells or EPCs decreased SOCS1 and increased STAT3 (signal transducer and activator of transcription 3) and VEGF‐C expression. When EPCs were simultaneously transfected with miR‐210 mimics and SOCS1, the expression of STAT3 and VEGF‐C was reversed.ConclusionsmiR‐210 promoted neovascularization and NPC migration via the SOCS1–STAT3–VEGF‐C pathway.

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Alzheimer’s disease (AD) is characterized by progressive cognitive impairment and by extensive neuronal loss associated with extracellular amyloid β-peptide (Aβ) plaques and intraneuronal tau pathology in temporal and parietal lobes. AD patients are at increased risk for epileptic seizures, and data from experimental models of AD suggest that aberrant neuronal network activity occurs early in the disease process before cognitive deficits and neuronal degeneration. The contributions of Aβ and/or tau pathologies to dysregulation of neuronal network activity are unclear. Using a transgenic mouse model of AD (3 × TgAD mice) in which there occurs differential age-dependent development of tau and Aβ plaque pathologies, we applied analysis of resting state functional magnetic resonance imaging regional homogeneity, a measure of local synchronous activity, to discriminate the effects of Aβ and tau on neuronal network activity throughout the brain. Compared to age-matched wild-type mice, 6- to 8-month-old 3 × TgAD mice exhibited increased regional homogeneity in the hippocampus and parietal and temporal cortices, regions with tau pathology but not Aβ pathology at this age. By 18–24 months of age, 3 × TgAD mice exhibited extensive tau and Aβ pathologies involving the hippocampus and multiple functionally related brain regions, with a spatial expansion of increased local synchronous activity to include those regions. Our findings demonstrate that age-related brain regional hypersynchronous activity is associated with early tau pathology in a mouse model, consistent with a role for early tau pathology in the neuronal circuit hyperexcitability that is believed to precede and contribute to neuronal degeneration in AD.