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

23 Citations (Scopus)

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

Fingerprint

Riluzole
Transcriptome
Glutamic Acid
Alzheimer Disease
Hippocampus
RNA
RNA Sequence Analysis
Amino Acid Transport System X-AG
Gene Expression
Aptitude
Synaptic Transmission
Rodentia
Immunohistochemistry
Learning
Polymerase Chain Reaction
Health
Brain
Genes

ASJC Scopus subject areas

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

Cite this

Pereira, A. C., Gray, J. D., Kogan, J. F., Davidson, R. L., Rubin, T. G., Okamoto, M., ... 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

Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole. / Pereira, A. C.; Gray, J. D.; Kogan, J. F.; Davidson, R. L.; Rubin, T. G.; Okamoto, M.; Morrison, John; McEwen, B. S.

In: Molecular Psychiatry, Vol. 22, No. 2, 01.02.2017, p. 296-305.

Research output: Contribution to journalArticle

Pereira, AC, Gray, JD, Kogan, JF, Davidson, RL, Rubin, TG, Okamoto, M, Morrison, J & McEwen, BS 2017, 'Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole', Molecular Psychiatry, vol. 22, no. 2, pp. 296-305. https://doi.org/10.1038/mp.2016.33
Pereira AC, Gray JD, Kogan JF, Davidson RL, Rubin TG, Okamoto M et al. Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole. Molecular Psychiatry. 2017 Feb 1;22(2):296-305. https://doi.org/10.1038/mp.2016.33
Pereira, A. C. ; Gray, J. D. ; Kogan, J. F. ; Davidson, R. L. ; Rubin, T. G. ; Okamoto, M. ; Morrison, John ; McEwen, B. S. / Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole. In: Molecular Psychiatry. 2017 ; Vol. 22, No. 2. pp. 296-305.
@article{873cbf78840e494e8be627f6f4564c75,
title = "Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole",
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.",
author = "Pereira, {A. C.} and Gray, {J. D.} and Kogan, {J. F.} and Davidson, {R. L.} and Rubin, {T. G.} and M. Okamoto and John Morrison and McEwen, {B. S.}",
year = "2017",
month = "2",
day = "1",
doi = "10.1038/mp.2016.33",
language = "English (US)",
volume = "22",
pages = "296--305",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole

AU - Pereira, A. C.

AU - Gray, J. D.

AU - Kogan, J. F.

AU - Davidson, R. L.

AU - Rubin, T. G.

AU - Okamoto, M.

AU - Morrison, John

AU - McEwen, B. S.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84961743204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961743204&partnerID=8YFLogxK

U2 - 10.1038/mp.2016.33

DO - 10.1038/mp.2016.33

M3 - Article

C2 - 27021815

AN - SCOPUS:84961743204

VL - 22

SP - 296

EP - 305

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 2

ER -