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The inflammatory cytokine, interleukin‐1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis
Author(s) -
Prow Natalie A.,
Irani David N.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05230.x
Subject(s) - astrocyte , spinal cord , glutamate receptor , astrogliosis , motor neuron , immunology , excitotoxicity , spinal cord injury , biology , neuroscience , medicine , central nervous system , receptor
Astrocytes remove glutamate from the synaptic cleft via specific transporters, and impaired glutamate reuptake may promote excitotoxic neuronal injury. In a model of viral encephalomyelitis caused by neuroadapted Sindbis virus (NSV), mice develop acute paralysis and spinal motor neuron degeneration inhibited by the AMPA receptor antagonist, NBQX. To investigate disrupted glutamate homeostasis in the spinal cord, expression of the main astroglial glutamate transporter, GLT‐1, was examined. GLT‐1 levels declined in the spinal cord during acute infection while GFAP expression was preserved. There was simultaneous production of inflammatory cytokines at this site, and susceptible animals treated with drugs that blocked IL‐1β release also limited paralysis and prevented the loss of GLT‐1 expression. Conversely, infection of resistant mice that develop mild paralysis following NSV challenge showed higher baseline GLT‐1 levels as well as lower production of IL‐1β and relatively preserved GLT‐1 expression in the spinal cord compared to susceptible hosts. Finally, spinal cord GLT‐1 expression was largely maintained following infection of IL‐1β‐deficient animals. Together, these data show that IL‐1β inhibits astrocyte glutamate transport in the spinal cord during viral encephalomyelitis. They provide one of the strongest in vivo links between innate immune responses and the development of excitotoxicity demonstrated to date.