Original Article

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

  • Molecular Psychiatry volume 22, pages 296305 (2017)
  • doi:10.1038/mp.2016.33
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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.

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    Data obtained from the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) Target Discovery Consortium data portal and can be accessed at HYPERLINK. ; doi:10.7303/syn2580853.

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Acknowledgements

This work was supported by DANA Foundation, the Rockefeller University Women & Science Initiative and Alzheimer’s Drug Discovery Foundation to ACP, NIH grant F32 MH102065 to JDG, NIA grant R37 AG06647 to JHM and partial support by grant # UL1 TR000043 from the National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS).

Author information

Author notes

    • A C Pereira
    •  & J D Gray

    These two authors contributed equally to this work.

Affiliations

  1. Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA

    • A C Pereira
    • , J D Gray
    • , J F Kogan
    • , R L Davidson
    • , T G Rubin
    • , M Okamoto
    •  & B S McEwen
  2. Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sports Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

    • M Okamoto
  3. Department of Neurology, School of Medicine, University of California Davis, Davis, CA, USA

    • J H Morrison

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Competing interests

The authors declare no conflict of interest.

Corresponding authors

Correspondence to A C Pereira or J D Gray.

Supplementary information

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)