Cited by 116Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

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

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Pereira, A C, Gray, J D, Kogan, J F, Davidson, R L, Rubin, T G, Okamoto, M, Morrison, J H, McEwen, B S·2017·Molecular Psychiatry

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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Crossref · 10.1038/mp.2016.33

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  • Downregulation of KCNIP3 in the brains of individuals with AD is associated with memory and learning.

    “Downregulation of KCNIP3 in the brains of individuals with AD is associated with memory and learning (63).”

    From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [63]

    The Results section reports that several genes are diminished in AD tissue, and the Discussion links some of those genes to learning and memory. Neither section identifies KCNIP3 or addresses whether its downregulation is associated with learning and memory; searches for KCNIP3 and its alternative names found no matching passage in our copy. (LLM, conf=0.73)

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  • A comparison of the effects of riluzole in rats against human Alzheimer's disease data sets revealed that many of the gene changes in Alzheimer's disease are reversed by riluzole.

    “Moreover, a comparison of the effects of riluzole in rats against human AD data sets revealed that many of the gene changes in Alzheimer's Disease (AD) are reversed by riluzole.”

    From Neurobiological and Systemic Effects of Chronic Stress (2017) · cites this paper as [55]

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  1. [52]Nothias F Fischer I Murray M Mirman S Vincent JD Expression of a phosphorylated isoform of MAP1B is maintained in adult central nervous system areas that retain capacity for structural plasticity. J Comp Neurol 1996 368 3 317 334 8725342
  2. [79]Esclaire F Lesort M Blanchard C Hugon J Glutamate toxicity enhances tau gene expression in neuronal cultures. J Neurosci Res 1997 49 3 309 318 9260742

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Authors
Pereira, A. C., Gray, J. D., Kogan, J. F., Davidson, R. L., Rubin, T. G., Okamoto, M., Morrison, J. H., & McEwen, B. S.
Affiliations
  • Rockefeller University (US)
  • University of Tsukuba (JP)
  • University of California, Davis (US)
Corresponding author
  • Pereira, A C
  • Gray, J D
Venue
Molecular Psychiatry
Published
2016-03-29
Volume
22
Issue
2
Pages
296-305
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W2324430454
Cited by
116
References
90
Citations by year
2026: 4 · 2025: 15 · 2024: 5 · 2023: 11 · 2022: 17 · 2021: 19 · 2020: 14 · 2019: 12 · 2018: 9 · 2017: 8 · 2016: 2
FWCI
8.32
Type
journal article
Language
en
Open access
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR000043, P51OD011107, UL1TR001866)
  • Japan Society for the Promotion of Science (16K16559)
  • National Institute on Aging (K76AG054772, R37AG006647)
  • National Institute of Mental Health (F32MH102065)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, riluzole, hippocampus, aging, gene expression profiling, synaptic transmission, memory, age-related cognitive decline, glutamate modulators
MeSH terms
Cognitive Aging, Age Factors, Aging, Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Hippocampus, Male, Memory, Synaptic Transmission, Rats, Sprague-Dawley, Neuroprotective Agents, Glutamic Acid, Riluzole, Excitatory Amino Acid Transporter 2, Rats, Transcriptome

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