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MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

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Abstract

Chronic cerebral hypoperfusion (CCH) characterized by global cerebral ischemia is an important risk factor contributing to the development of dementia. MicroRNAs (miRNAs) play important roles in the cellular adaptation to long-term ischemia/hypoxia by turning off or on the expression of target genes. MiR-181c is widely expressed in the nervous system, and tripartite motif 2 (TRIM2) is one of its target genes. In this work, we had identified that progressive spatial memory deficiency was induced in the bilateral common carotid artery occlusion (2-VO) rat models. Meanwhile, inhibition of miR-181c expression and upregulation of TRIM2 in the hippocampus of 2-VO rats were found accompanying with reduction in the dendritic branching and dendrite spine density of the hippocampal neurons. Viral vector-mediated miR-181c delivery might improve the cognitive deficiency via TRIM2 on neurofilament light (NF-L) ubiquitination resulting in remodeling of the hippocampal neurons as well as increase in N-methyl-d-aspartate receptor 1 (NR1) subunit cell surface expression. Meanwhile, miR-181c might rescue the cellular activity from ischemia/hypoxia. These results indicated a novel miRNA-mediated mechanism involving miR-181c and TRIM2 in the cognitive impairment induced by CCH and provided a rationale for the development of miRNA-based strategies for prevention of dementia.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (No. 81271310) and Key project of science and technology program of Beijing Municipal Education Commission (No. KZ201610025021).

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  1. Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China

    Chen Fang, Qian Li, Guowen Min, Min Liu, Jing Cui, Jing Sun & Liang Li

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Fig. S1

Nissl’s staining of hippocampus from sham-operated and 2-VO rats (upper panels) (Scale bar=200 μm). The bottom panels were high magnifications of labeled box, respectively (Scale bar=20 μm). (JPEG 122 kb)

Fig. S2

Fluorescent observation of brain slices with lenti-vector injection. (A) Brain slices were examined under inverted fluorescent microscope. Green fluorescence was observed in CA1 area of hippocampus from sham+NC group. (B) High magnification of labeled box in A (Scale bar=200 μm). (JPEG 564 kb)

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Fang, C., Li, Q., Min, G. et al. MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats. Mol Neurobiol 54, 8370–8385 (2017). https://doi.org/10.1007/s12035-016-0268-6

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