Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole

Mol Psychiatry. 2017 Feb;22(2):296-305. doi: 10.1038/mp.2016.33. Epub 2016 Mar 29.


Alzheimer's disease (AD) and age-related cognitive decline represent a growing health burden and involve the hippocampus, a vulnerable brain region implicated in learning and memory. To understand the molecular effects of aging on the hippocampus, this study characterized the gene expression changes associated with aging in rodents using RNA-sequencing (RNA-seq). The glutamate modulator, riluzole, which was recently shown to improve memory performance in aged rats, prevented many of the hippocampal age-related gene expression changes. A comparison of the effects of riluzole in rats against human AD data sets revealed that many of the gene changes in AD are reversed by riluzole. Expression changes identified by RNA-Seq were validated by qRT-PCR open arrays. Riluzole is known to increase the glutamate transporter EAAT2's ability to scavenge excess glutamate, regulating synaptic transmission. RNA-seq and immunohistochemistry confirmed an increase in EAAT2 expression in hippocampus, identifying a possible mechanism underlying the improved memory function after riluzole treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / genetics
  • Aging / metabolism
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Animals
  • Cognition / drug effects*
  • Cognitive Aging / physiology
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 2 / drug effects*
  • Glutamic Acid / metabolism
  • Hippocampus / metabolism
  • Male
  • Memory / drug effects
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Riluzole / metabolism
  • Riluzole / therapeutic use*
  • Synaptic Transmission / physiology
  • Transcriptome / genetics


  • Excitatory Amino Acid Transporter 2
  • Neuroprotective Agents
  • Glutamic Acid
  • Riluzole