Sera from children with autism alter proliferation of human neuronal progenitor cells exposed to oxidation

Neurotox Res. 2009 Jul;16(1):87-95. doi: 10.1007/s12640-009-9052-y. Epub 2009 Apr 18.

Abstract

Altered brain development during embryogenesis and early postnatal life has been hypothesized to be responsible for the abnormal behaviors of people with autism. The specific genetic background that alters vulnerability to some environmental insults has been suggested in the etiology of autism; however, the specific pathomechanisms have not been identified. Recently, we showed that sera from children with autism alter the maturation of human neuronal progenitor cells (NPCs) in culture. Results suggest that pre-programmed neurogenesis, i.e., neuronal proliferation, migration, differentiation, growth, and circuit organization, can be affected differently by factors present in autistic sera. In this report, we tested the effect of autistic sera on the vulnerability of NPCs to oxidative stress-a recognized risk factor of autism. We found that mild oxidative stress reduced proliferation of differentiating NPCs but not immature NPCs. This decrease of proliferation was less prominent in cultures treated with sera from children with autism than from age-matched controls. These results suggest that altered response of NPCs to oxidative stress may play a role in the etiology of autism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Analysis of Variance
  • Apoptosis / drug effects
  • Autistic Disorder / blood*
  • Bromodeoxyuridine / metabolism
  • Carbocyanines / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Doublecortin Domain Proteins
  • Embryonic Stem Cells / drug effects*
  • Female
  • Ferrous Compounds / pharmacology
  • Fetus
  • Humans
  • Infant
  • Intermediate Filament Proteins / metabolism
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Oxidative Stress / physiology*
  • Phosphopyruvate Hydratase / metabolism
  • SOXB1 Transcription Factors / metabolism
  • Serum / chemistry*
  • Time Factors
  • Tubulin / metabolism

Substances

  • Carbocyanines
  • Doublecortin Domain Proteins
  • Ferrous Compounds
  • Intermediate Filament Proteins
  • MAP2 protein, human
  • Microtubule-Associated Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nestin
  • Neuropeptides
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • TO-PRO-3
  • TUBB3 protein, human
  • Tubulin
  • Phosphopyruvate Hydratase
  • Bromodeoxyuridine
  • ferrous chloride