Knockdown of MicroRNA-1 in the Hippocampus Ameliorates Myocardial Infarction Induced Impairment of Long-Term Potentiation

Cellular Physiology and Biochemistry

Ji-Chao Ma¹ 

关键词: Heart;    Hippocampus;    Cognitive impairment;    MicroRNA-1;    BDNF;    long-term potentiation;   

DOI  :  10.1159/000494657

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Backgrounds/Aims It has been reported that myocardial infarction (MI) is a risk factor for vascular dementia. However, the molecular mechanism remains largely unknown. Methods MI mice were generated by ligation of the left coronary artery (LCA) for 4 weeks. Passive and active avoidance tests were performed to evaluate the cognitive ability of MI mice. A theta-burst stimulation (TBS) protocol was applied to elicit long-term potentiation (LTP) of the perforant pathway-dentate gyrus synapse (PP-DG). Western blot analysis was employed to assess protein levels. Results In this study, we demonstrated that after 4 weeks of MI, C57BL/6 mice had significantly impaired memory. Compared with the sham group, in vivo physiological recording in the MI group revealed significantly decreased amplitude of population spikes (PS) with no effect on the latency and duration of the stimulus-response curve. The amplitude of LTP was markedly decreased in the MI group compared with the sham group. Further examination showed that the expression of the TBS-LTP-related proteins BDNF, GluA1 and phosphorylated GluA1 were all decreased in the MI group compared with those in the sham group. Strikingly, all these changes were prevented by hippocampal stereotaxic injection of an anti-miR-1 oligonucleotide fragment carried by a lentivirus vector (lenti-pre-AMO-1). Conclusion MI induced cognitive decline and TBS-LTP impairment, and decreased BDNF and GluA1 phosphorylation levels from overexpression of miR-1ated were involved in this process.

【 授权许可】

CC BY-NC-ND