Immune signaling in the developing brain in mouse models of autism

  • Awarded: 2014
  • Award Type: Targeted: Innate Immune System
  • Award #: 321998

Immune‐related genes and immune responses to environmental stimuli are receiving attention due to their potential involvement in several neurodevelopmental disorders, including autism. Immune‐related genes have been associated with autism and maternal infection has been found to be the most compelling environmental risk factor for the disorder. Additionally, immune molecules have been shown to play many roles throughout brain development, including the initial establishment of synaptic connections, as well as synaptic plasticity.

These findings converged to create the hypothesis that immune dysregulation from genetic mutations or environmental exposures alters the expression and function of immune molecules in the brain, causing changes in synaptic connectivity, which eventually leads to the behaviors diagnostic of autism.

Recently, Kimberley McAllister and her colleagues at the University of California, Davis provided evidence supporting this hypothesis using a mouse model of maternal immune activation (MIA), which exhibits the three core behavioral phenotypes and the neuropathological signatures of autism. Several classes of immune molecules, including cytokines and major histocompatibility complex I (MHCI) molecules, are altered in the brains of MIA mouse offspring throughout development1,2The elevation of MHCI on neurons in these pups at birth mediates a significant deficit in the ability of cortical neurons to form synapses2. However, it is not known if connections are altered in the brains of MIA pups after birth and, if so, whether those changes are mediated by MHCI expression. In addition, the effect of MHCI expression on autism‐related behaviors and its involvement in MIA‐induced autism behaviors in offspring remain unknown.

McAllister and her colleagues aim to test the hypothesis that MIA causes autism‐related behaviors in offspring by altering neural connectivity via changes in neuronal MHCI expression. If successful, results from this project have the potential to identify novel molecular targets for development of diagnostic tools and therapeutic interventions to ameliorate the effects of neuroimmune dysregulation on brain connections and behavior.



1.Garay P.A. et al. Brain Behav. Immun. 31, 54-68 (2013) PubMed
2.Elmer B.M. et al. J. Neurosci. 33, 13791-13804 (2013) PubMed
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