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Maternal immune activation and abnormal brain development across CNS disorders.

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Maternal infection during pregnancy can lead to neurodevelopmental disorders in children. Maternal immune activation (mIA) primes microglia, increasing offspring risk for conditions like autism, schizophrenia, and neurodegenerative diseases.

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Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Epidemiological studies link maternal infection to offspring schizophrenia and autism.
  • Maternal immune activation (mIA) in animal models causes offspring neurochemical and behavioral abnormalities.
  • Microglial priming is a key consequence of mIA, mediating long-term neuronal dysfunction.

Purpose of the Study:

  • To review evidence linking mIA to a spectrum of CNS disorders.
  • To discuss the role of genetic and environmental interactions in mIA's phenotypic outcomes.
  • To examine clinical trials targeting immune pathways in mIA-related diseases.

Main Methods:

  • Literature review of epidemiological and preclinical studies on mIA.
  • Analysis of animal models demonstrating mIA-induced neurodevelopmental effects.
  • Evaluation of current clinical trials for mIA-associated conditions.

Main Results:

  • mIA is a shared risk factor across diverse CNS disorders, including autism, schizophrenia, epilepsy, cerebral palsy, Alzheimer's, and Parkinson's diseases.
  • Phenotypic outcomes in offspring are influenced by interactions between genetic and additional environmental factors.
  • Clinical trials are investigating immune-targeted therapies for mIA-related diseases.

Conclusions:

  • mIA represents a significant environmental risk factor with broad implications for central nervous system disorders.
  • Understanding gene-environment interactions is crucial for deciphering the diverse outcomes of mIA.
  • Targeting immune pathways offers potential therapeutic strategies for prevention and treatment.