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.
authors.affiliation: Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Gray
authors.affiliation: Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Kogan
authors.affiliation: Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Davidson
authors.affiliation: Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Rubin
authors.affiliation: Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.|Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sports Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Neurology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Morrison
authors.affiliation: Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D000066492:Cognitive Aging / Q000502:physiology; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000378:metabolism / Q000627:therapeutic use*; D009435:Synaptic Transmission / Q000502:physiology; D059467:Transcriptome / Q000235:genetics
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D019782:Riluzole