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

A. C. Pereira, J. D. Gray, J. F. Kogan, R. L. Davidson, T. G. Rubin, M. Okamoto, John Morrison, B. S. McEwen

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)296-305
Number of pages10
JournalMolecular Psychiatry
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Pereira, A. C., Gray, J. D., Kogan, J. F., Davidson, R. L., Rubin, T. G., Okamoto, M., Morrison, J., & McEwen, B. S. (2017). Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole. Molecular Psychiatry, 22(2), 296-305. https://doi.org/10.1038/mp.2016.33