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Riluzole Partially Rescues Age-Associated, but not LPS-Induced, Loss of Glutamate Transporters and Spatial Memory

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Abstract

Impaired memory may result from synaptic glutamatergic dysregulation related to chronic neuroinflammation. GLT1 is the primary excitatory amino acid transporter responsible for regulating extracellular glutamate levels in the hippocampus. We tested the hypothesis that if impaired spatial memory results from increased extracellular glutamate due to age or experimentally induced chronic neuroinflammation in the hippocampus, then pharmacological augmentation of the glutamate transporter GLT1 will attenuate deficits in a hippocampal-dependent spatial memory task. The profile of inflammation-related genes and proteins associated with normal aging, or chronic neuroinflammation experimentally-induced via a four-week LPS infusion into the IVth ventricle, were correlated with performance in the Morris water maze following treatment with Riluzole, a drug that can enhance glutamate clearance by increasing GLT1 expression. Age-associated inflammation was qualitatively different from LPS-induced neuro-inflammation in young rats. LPS produced a pro-inflammatory phenotype characterized by increased IL-1ß expression in the hippocampus, whereas aging was not associated with a strong central pro-inflammatory response but with a mixed peripheral immune phenotype. Riluzole attenuated the spatial memory impairment, the elevation of serum cytokines and the decrease in GLT1 gene expression in Aged rats, but had no effect on young rats infused with LPS. Our findings highlight the therapeutic potential of reducing glutamatergic function upon memory impairment in neurodegenerative diseases associated with aging.

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Acknowledgments

Dr. Glenn Lin for sharing control tissue for GLT1 staining. Supported by U.S. Public Health Service, RO1 AG030331, RO1 AG037320 to GLW and The Ohio State University Women and Philanthropy Program.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Psychology, Ohio State University, 1835 Neil Avenue, Columbus, OH, 43210, USA

    Holly M. Brothers, Isabelle Bardou, Roxanne M. Kaercher & Gary L. Wenk

  2. Department of Neuroscience, Ohio State University, Columbus, OH, 43210, USA

    Sarah C. Hopp, Angela W. Corona, Ashley M. Fenn, Jonathan P. Godbout & Gary L. Wenk

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  1. Holly M. Brothers
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  2. Isabelle Bardou
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  3. Sarah C. Hopp
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  4. Roxanne M. Kaercher
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  5. Angela W. Corona
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  6. Ashley M. Fenn
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  7. Jonathan P. Godbout
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  8. Gary L. Wenk
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Correspondence to Gary L. Wenk.

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Brothers, H.M., Bardou, I., Hopp, S.C. et al. Riluzole Partially Rescues Age-Associated, but not LPS-Induced, Loss of Glutamate Transporters and Spatial Memory. J Neuroimmune Pharmacol 8, 1098–1105 (2013). https://doi.org/10.1007/s11481-013-9476-2

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  • DOI: https://doi.org/10.1007/s11481-013-9476-2

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