Microglia as Biosensors and Effectors of Neurodysfunction

Abstract

Systemic inflammation has been hypothesized to induce or exacerbate the onset and progression of autism spectrum disorders. Dendritic spines receive the majority of excitatory synapses in the brain and play a critical role in cognitive development and learning. Defects in dendritic spine formation have been found in the brains of patients with some autistic spectrum disorders. Here we explored the effects of systemic inflammation on secondary neuroinflammation and dendritic spine development. We found that systemic inflammation triggered a much greater influx of macrophages into the young developing brain than into the mature brain without causing changes in dendritic spine formation or maturation. Our data suggest that this may be due to developmentally regulated changes in CNS-intrinsic immunity. Specifically, the expression of high levels of anti-inflammatory, neuroprotective receptors by CNS-resident microglia may be required to sustain optimal brain function in infancy and childhood when individuals are likely to be exposed to common inflammatory insults. Our completed studies provide a de facto screen to identify genetic and/or environmental factor that alter the normal developmental progression of CNS-intrinsic immunity and/or CNS intrinsic responses to systemic inflammation reported in our studies.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2010
Accession Number
ADA546077

Entities

People

  • Monica J. Carson

Organizations

  • University of California, Riverside

Tags

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Autism
  • Biosensors
  • Brain
  • California
  • Cells
  • Cellular Structures
  • Central Nervous System
  • Diseases And Disorders
  • Immune System
  • Immunity
  • Macrophages
  • Nervous System
  • Neurodevelopmental Disorders
  • Neuroglia
  • Neurons
  • Synapses

Fields of Study

  • Medicine

Readers

  • Child and Adolescent Substance Abuse Science in Autism Spectrum Disorders.
  • Immunology and Pathology
  • Neuroscience

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech