title: Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles.
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.
authors: Department of Psychology, University of Hawaii, 2530 Dole Street, Honolulu, HI 96822, USA.
authors: Brandon L
authors: BL
authors: Pearson
authors: Michael J
authors: MJ
authors: Corley
authors: Amy
authors: A
authors: Vasconcellos
authors: D Caroline
authors: DC
authors: Blanchard
authors: Robert J
authors: RJ
authors: Blanchard
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002675:Child, Preschool; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006497:Heparan Sulfate / Q000172:deficiency*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055495:Neurogenesis / Q000502:physiology; D014015:Tissue Banks; D055815:Young Adult
chemical_list: D006497:Heparan Sulfate; D007797:Laminin