Journal
MOLECULAR PSYCHIATRY
Volume 22, Issue 2, Pages 296-305Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2016.33
Keywords
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Funding
- DANA Foundation
- Rockefeller University Women & Science Initiative
- Alzheimer's Drug Discovery Foundation
- NIH [F32 MH102065]
- NIA [R37 AG06647]
- National Center for Research Resources [UL1 TR000043]
- National Center for Advancing Translational Sciences (NCATS)
- Grants-in-Aid for Scientific Research [16K16559] Funding Source: KAKEN
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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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