Riluzole partially rescues age-associated, but not LPS-induced, loss of glutamate transporters and spatial memory

Holly M. Brothers, Isabelle Bardou, Sarah C. Hopp, Roxanne M. Kaercher, Angela W. Corona, Ashley M. Fenn, Jonathan P. Godbout, Gary L. Wenk

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1098-1105
Number of pages8
JournalJournal of Neuroimmune Pharmacology
Issue number5
StatePublished - Dec 2013
Externally publishedYes


  • Animal models
  • Glutamate
  • Neuroinflammation
  • Rats
  • Riluzole

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology


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