Dataset Information

MicroRNA-26b Regulates the Microglial Inflammatory Response in Hypoxia/Ischemia and Affects the Development of Vascular Cognitive Impairment.

ABSTRACT: Background: Microglia play an important role in the central nervous system as immune cells and are often activated by post-ischemic injury. MicroRNAs are small endogenous RNAs affecting many complex cellular biological functions that are involved in neurodegenerative and cerebrovascular diseases. Previous studies have shown that microRNA-26b (miR-26b) is downregulated in BV-2 cells exposed to oxygen-glucose deprivation (OGD). Objective: This study aimed to investigate how miR-26b regulates microglial activation and its neurotoxicity as well as the effect of miR-26b on vascular cognitive impairment (VCI). Methods: Here, we used PCR to detect the mRNA expression of miR-26b and cytokines, western blot for the protein expression of cytokines, and the live/dead assay for neuronal apoptosis. In addition, we employed a luciferase assay to identify the possible target genes of miR-26b. Furthermore, we studied the effects of cerebral ischemia by bilateral common carotid artery occlusion (BCCAO) in rats. We used staining to identify neurons and microglia, and we tested cognitive function by the T-maze test. Results: Our results showed that OGD activated microglia and increased the expression of interleukin (IL)-6 and other cytokines. Similarly, BCCAO activated microglia and increased the expression of IL-6 in the hippocampal CA1 area. We further found that miR-26b decreased the number of activated microglia and targeted IL-6. Moreover, miR-26b expression attenuated microglial activation, inflammation, neurotoxicity and VCI. Conclusion: Our results suggested that miR-26b is involved in microglial activation and neurotoxicity in hypoxia/ischemia via IL-6. Therefore, increasing miR-26b expression may improve cognitive function.

SUBMITTER: Kang YC

PROVIDER: S-EPMC6002499 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MicroRNA-26b Regulates the Microglial Inflammatory Response in Hypoxia/Ischemia and Affects the Development of Vascular Cognitive Impairment.

Kang Yuan-Cheng YC Zhang Li L Su Ying Y Li Yue Y Ren Wen-Lei WL Wei Wen-Shi WS

Frontiers in cellular neuroscience 20180608

<b>Background:</b> Microglia play an important role in the central nervous system as immune cells and are often activated by post-ischemic injury. MicroRNAs are small endogenous RNAs affecting many complex cellular biological functions that are involved in neurodegenerative and cerebrovascular diseases. Previous studies have shown that microRNA-26b (miR-26b) is downregulated in BV-2 cells exposed to oxygen-glucose deprivation (OGD). <b>Objective:</b> This study aimed to investigate how miR-26b r ...[more]

PMID: 29937716

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Project description:ImportanceCerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and β-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins.ObjectiveTo determine the synergistic effects of β-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI).Design, setting, and participantsA cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes.Main outcomes and measuresWe measured β-amyloid burden using positron emission tomography with carbon 11-labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients' cognitive impairment.ResultsOn evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI.Conclusions and relevanceMost patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase β-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.

Project description:Vascular dementia (VD) is the most common form of dementia in elderly people. However, little is understood about the role of microRNAs (miRNAs) involved in cognitive impairment in early VD. Here, a VD model induced by chronic cerebral ischemia and fetal bovine serum (FBS)-free cell model that detects synapse formation was established to investigate the function of miRNAs in early VD. The microarray analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) showed that miR-210-5p increased significantly in the hippocampus of rats with 4 weeks of ischemia. The VD model rats also displayed significant cognitive deficits and synaptic loss. The overexpression of miR-210-5p decreased the synaptic number in primary hippocampal neurons, whereas specific suppression of miR-210-5p resulted in the formation of more synapses. Additionally, intracerebroventricular (ICV) injection of miR-210-5p agomir to VD rats aggravated phenotypes of cognitive impairment and synaptic loss. These VD-induced phenotypes were effectively attenuated by miR-210-5p antagomir. Moreover, bioinformatic prediction revealed that synaptosomal-associated protein of 25 KDa (Snap25) mRNA is targeted by miR-210-5p. The miR-210-5p decreased the luciferase activities of 3' untranslated region (3'UTR) of Snap25 mRNA. Mutation of predicted miR-210-5p binding sites in the 3' UTR of Snap25 mRNA abolished the miR-210-5p-induced decrease in luciferase activity. Western blot and immunofluorescence staining confirmed that miR-210-5p targets Snap25. Finally, RT-quantitative PCR (qPCR) and immunofluorescence staining detected that miR-210-5p agomir downregulated Snap25 expression in the cornu ammonis1 (CA1) region of hippocampi in VD rats, whereas miR-210-5p antagomir upregulated Snap25 expression. Altogether, miR-210-5p contributes to cognitive impairment in chronic ischemia-induced VD model through the regulation of Snap25 expression, which potentially provides an opportunity to develop a new therapeutic strategy for VD.

Dataset Information

MicroRNA-26b Regulates the Microglial Inflammatory Response in Hypoxia/Ischemia and Affects the Development of Vascular Cognitive Impairment.

Publications

MicroRNA-26b Regulates the Microglial Inflammatory Response in Hypoxia/Ischemia and Affects the Development of Vascular Cognitive Impairment.

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