Neuroimmunologic and Neurotrophic Interactions in Autism Spectrum Disorders: Relationship to Neuroinflammation

Neuromolecular Med. 2018 Jun;20(2):161-173. doi: 10.1007/s12017-018-8488-8. Epub 2018 Apr 24.

Abstract

Autism spectrum disorders (ASD) are the most prevalent set of pediatric neurobiological disorders. The etiology of ASD has both genetic and environmental components including possible dysfunction of the immune system. The relationship of the immune system to aberrant neural circuitry output in the form of altered behaviors and communication characterized by ASD is unknown. Dysregulation of neurotrophins such as BDNF and their signaling pathways have been implicated in ASD. While abnormal cortical formation and autistic behaviors in mouse models of immune activation have been described, no one theory has been described to link activation of the immune system to specific brain signaling pathways aberrant in ASD. In this paper we explore the relationship between neurotrophin signaling, the immune system and ASD. To this effect we hypothesize that an interplay of dysregulated immune system, synaptogenic growth factors and their signaling pathways contribute to the development of ASD phenotypes.

Keywords: ASD; Brain-derived neurotrophic factor; Cytokines; Microglia; PI3 kinase signaling; T cells.

Publication types

  • Review

MeSH terms

  • Autism Spectrum Disorder / etiology
  • Autism Spectrum Disorder / immunology
  • Autism Spectrum Disorder / therapy*
  • Brain-Derived Neurotrophic Factor / immunology
  • Child
  • Gene-Environment Interaction
  • Humans
  • Immunization / adverse effects
  • Infections / immunology
  • Intercellular Signaling Peptides and Proteins / physiology
  • Microglia / immunology
  • Models, Immunological
  • Nerve Growth Factors / physiology
  • Neuroimmunomodulation
  • Receptor Protein-Tyrosine Kinases / immunology
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology
  • Transforming Growth Factor beta / physiology
  • Wnt Signaling Pathway / immunology

Substances

  • Brain-Derived Neurotrophic Factor
  • Intercellular Signaling Peptides and Proteins
  • Nerve Growth Factors
  • Transforming Growth Factor beta
  • BDNF protein, human
  • Receptor Protein-Tyrosine Kinases