Promotive role of microRNA‑150 in hippocampal neurons apoptosis in vascular dementia model rats

Mol Med Rep. 2021 Apr;23(4):257. doi: 10.3892/mmr.2021.11896. Epub 2021 Feb 12.

Abstract

Cognitive impairment is one of the primary features of vascular dementia (VD). However, the specific mechanism underlying the regulation of cognition function in VD is not completely understood. The present study aimed to explore the effects of microRNA (miR)‑150 on VD. To determine the effects of miR‑150 on cognitive function and hippocampal neurons in VD model rats, rats were subjected to intracerebroventricular injections of miR‑150 antagomiR. The Morris water maze test results demonstrated that spatial learning ability was impaired in VD model rats compared with control rats. Moreover, compared with antagomiR negative control (NC), miR‑150 antagomiR alleviated cognitive impairment and enhanced memory ability in VD model rats. The triphenyltetrazolium chloride, Nissl staining and immunohistochemistry results further demonstrated that miR‑150 knockdown improved the activity of hippocampal neurons in VD model rats compared with the antagomiR NC group. To validate the role of miR‑150 in neurons in vitro, the PC12 cell line was used. The flow cytometry and Hoechst 33342/PI double staining results indicated that miR‑150 overexpression significantly increased cell apoptosis compared with the mimic NC group. Moreover, the dual‑luciferase reporter gene assay results indicated that miR‑150 targeted HOXA1 and negatively regulated HOXA1 expression. Therefore, the present study indicated that miR‑150 knockdown ameliorated VD symptoms by upregulating HOXA1 expression in vivo and in vitro.

Keywords: vascular dementia; microrna‑150; homobox a1; hippocampal neurons; cognitive impairment; microrna‑150 antagomiR.

MeSH terms

  • Animals
  • Antagomirs / administration & dosage
  • Antagomirs / genetics
  • Apoptosis / genetics*
  • Cognition / physiology
  • Dementia, Vascular / genetics*
  • Disease Models, Animal*
  • Gene Expression Regulation
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Maze Learning / physiology
  • MicroRNAs / genetics*
  • Neurons / metabolism*
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Spatial Learning / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Antagomirs
  • Homeodomain Proteins
  • MIRN150 microRNA, rat
  • MicroRNAs
  • Transcription Factors
  • homeobox A1 protein

Grants and funding

The present study was supported by the Scientific Research Project of Heilongjiang Health Committee (grant nos. 2017-500 and 2017-496).