Upregulation of microRNA-196a improves cognitive impairment and alleviates neuronal damage in hippocampus tissues of Alzheimer's disease through downregulating LRIG3 expression

J Cell Biochem. 2019 Oct;120(10):17811-17821. doi: 10.1002/jcb.29047. Epub 2019 May 22.

Abstract

Purpose: This study is launched to uncover the inner function of microRNA-196a (miR-196a) on cognitive dysfunction and neuronal damage in Alzheimer's disease (AD) rats through regulating the PI3K/Akt signaling pathway.

Methods: The establishment of AD rat model was performed by a microinjection of Aβ25-35 . miR-196a and LRIG3 expression was detected, and the putative binding site between them was also determined. The spatial learning and memory capability, the hippocampal neurons ultrastructure as well as the survival, and apoptosis of hippocampal neurons of rats were observed. The expression of apoptosis-associated protein, oxidative stress index, and inflammatory factors as well as the PI3K/Akt pathway-related factors was determined.

Results: Initially, decreased miR-196a and increased LRIG3 were exhibited in hippocampus tissues of AD rats. In addition, restored miR-196a and deleted LRIG3 ameliorated spatial learning and memory capability, suppressed the pathological injury, induced the survival, and suppressed the apoptosis of hippocampal neurons, as well as inhibited oxidative stress injury together with inflammatory injury in AD rats. Furthermore, upregulation of miR-196a activated the PI3/Akt pathway in AD rats.

Conclusion: This current study suggests that upregulation of miR-196a and downregulation of LRIG3 improve cognitive impairment and alleviate neuronal damage in hippocampus tissues in AD rats via the modulation of the PI3K/Akt pathway.

Keywords: Alzheimer's disease; LRIG3; PI3K/Akt signaling pathway; cognitive impairment; hippocampus tissue; microRNA-196a; neuronal damage.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Animals
  • Base Sequence
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / physiopathology
  • Down-Regulation / genetics*
  • Hippocampus / pathology*
  • Inflammation / pathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Memory
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / metabolism
  • Neurons / pathology*
  • Oxidative Stress
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Spatial Learning
  • Survival Analysis
  • Up-Regulation / genetics*

Substances

  • Membrane Proteins
  • MicroRNAs
  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-akt