miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline

Int J Mol Sci. 2018 Aug 8;19(8):2323. doi: 10.3390/ijms19082323.

Abstract

Microribonucleic acids (miRNAs) play a pivotal role in numerous aspects of the nervous system and are increasingly recognized as key regulators in neurodegenerative diseases. This study hypothesized that miR-34c, a miRNA expressed in mammalian hippocampi whose expression level can alter the hippocampal dendritic spine density, could induce memory impairment akin to that of patients with Alzheimer's disease (AD) in mice. In this study, we showed that miR-34c overexpression in hippocampal neurons negatively regulated dendritic length and spine density. Hippocampal neurons transfected with miR-34c had shorter dendrites on average and fewer filopodia and spines than those not transfected with miR-34c (control mice). Because dendrites and synapses are key sites for signal transduction and fundamental structures for memory formation and storage, disrupted dendrites can contribute to AD. Therefore, we supposed that miR-34c, through its effects on dendritic spine density, influences synaptic plasticity and plays a key role in AD pathogenesis.

Keywords: Alzheimer’s disease; dendritic spine; miR-34c.

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Animals
  • Dendritic Spines / genetics*
  • Dendritic Spines / pathology
  • Gene Expression Regulation / genetics
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Memory / physiology
  • Memory Disorders / genetics*
  • Memory Disorders / pathology
  • Mice
  • MicroRNAs / genetics*
  • Neuronal Plasticity / genetics
  • Neurons / metabolism
  • Neurons / pathology
  • Synapses / genetics
  • Synapses / pathology

Substances

  • MIRN34 microRNA, human
  • MicroRNAs