Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

Behav Brain Res. 2013 Apr 15;243:138-45. doi: 10.1016/j.bbr.2012.12.062. Epub 2013 Jan 11.

Abstract

Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n=4) and age-matched typically developing (TD) individuals (n=4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Autistic Disorder / metabolism*
  • Autistic Disorder / pathology
  • Cell Proliferation
  • Child, Preschool
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Heparitin Sulfate / deficiency*
  • Humans
  • Laminin / metabolism
  • Lateral Ventricles / cytology
  • Lateral Ventricles / metabolism*
  • Lateral Ventricles / pathology
  • Male
  • Middle Aged
  • Neurogenesis / physiology
  • Tissue Banks
  • Young Adult

Substances

  • Laminin
  • Heparitin Sulfate