Frontiers in Behavioral Neuroscience (Dec 2015)

Targeting glia with N-Acetylcysteine modulates brain glutamate and behaviours relevant to neurodevelopmental disorders in C57BL/6J mice

  • Alice Marie Sybille Durieux,
  • Cathy eFernandes,
  • Declan eMurphy,
  • Marie eLabouesse,
  • Sandra eGiovanoli,
  • Sandra eGiovanoli,
  • Urs eMeyer,
  • Urs eMeyer,
  • Qi eLi,
  • Po-Wah eSo,
  • Grainne eMcAlonan

DOI
https://doi.org/10.3389/fnbeh.2015.00343
Journal volume & issue
Vol. 9

Abstract

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An imbalance between excitatory (E) glutamate and inhibitory (I) GABA transmission may underlie neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC), which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in-vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviours relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span.

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