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Does microglial dysfunction play a role in autism and Rett syndrome?

Published online by Cambridge University Press:  30 April 2012

Izumi Maezawa*
Affiliation:
M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Instituteand Department of Pathology and Laboratory Medicine, Sacramento, CA, USA
Marco Calafiore
Affiliation:
M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Instituteand Department of Pathology and Laboratory Medicine, Sacramento, CA, USA
Heike Wulff
Affiliation:
Department of Pharmacology, University of California Davis, Davis, CA, USA
Lee-Way Jin*
Affiliation:
M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Instituteand Department of Pathology and Laboratory Medicine, Sacramento, CA, USA Alzheimer's Disease Center, University of California Davis Medical Center, Sacramento, CA, USA
*
Correspondence should be addressed to: Izumi Maezawa or Lee-Way Jin, Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA 95817USA phone: 916-703-0272 or 916-703-0392 email: imaezawa@ucdavis.edu or lee-way.jin@ucdmc.ucdavis.edu
Correspondence should be addressed to: Izumi Maezawa or Lee-Way Jin, Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA 95817USA phone: 916-703-0272 or 916-703-0392 email: imaezawa@ucdavis.edu or lee-way.jin@ucdmc.ucdavis.edu

Abstract

Autism spectrum disorders (ASDs) including classic autism is a group of complex developmental disabilities with core deficits of impaired social interactions, communication difficulties and repetitive behaviors. Although the neurobiology of ASDs has attracted much attention in the last two decades, the role of microglia has been ignored. Existing data are focused on their recognized role in neuroinflammation, which only covers a small part of the pathological repertoire of microglia. This review highlights recent findings on the broader roles of microglia, including their active surveillance of brain microenvironments and regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis. Emerging evidence suggests that microglia respond to pre- and postnatal environmental stimuli through epigenetic interface to change gene expression, thus acting as effectors of experience-dependent synaptic plasticity. Impairments of these microglial functions could substantially contribute to several major etiological factors of autism, such as environmental toxins and cortical underconnectivity. Our recent study on Rett syndrome, a syndromic autistic disorder, provides an example that intrinsic microglial dysfunction due to genetic and epigenetic aberrations could detrimentally affect the developmental trajectory without evoking neuroinflammation. We propose that ASDs provide excellent opportunities to study the influence of microglia on neurodevelopment, and this knowledge could lead to novel therapies.

Type
Reviews
Copyright
Copyright © Cambridge University Press 2012

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References

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