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

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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. http://dx.doi.org/doi:10.7303/syn2580853; 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).

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Correspondence to A C Pereira or J D Gray.

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Pereira, A., Gray, J., Kogan, J. et al. Age and Alzheimer’s disease gene expression profiles reversed by the glutamate modulator riluzole. Mol Psychiatry 22, 296–305 (2017) doi:10.1038/mp.2016.33

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