Immune Transcript disturbances in temp cortex of ASD brains

[Guest guest]

Title: Immune transcript disturbances in temporal cortex of autistic brains

Location: San Diego Convention Center: Halls B-H

Presentation Start/End Time: Saturday, Nov 03, 2007, 3:00 PM - 4:00 PM

Authors: *K. A. GARBETT1, P. EBERT1, C. LINTAS3,4, K. MIRNICS1,2, A. M.

PERSICO3,4;

1Psychiatry, 2Kennedy Ctr. for Human Develop., Vanderbilt Univ.,

Nashville, TN; 3Lab. of Mol. Psychiatry and Neurogenetics, Univ. Campus

Bio-Medico, Rome, Italy; 4IRCCS Fondazione Santa Lucia, Rome, Italy

Autistic spectrum disorder (ASD) is a common neurodevelopmental disorder

characterized by communicative, social and behavioral dysfunctions. It

is considered to be a result of complex interactions of genetic,

environmental and immunological factors. In order to elucidate the

molecular events occurring in autistic brains we attempted to describe

the global transcriptome changes in temporal cortical tissue from the

postmortem brains of autistic individuals using oligonucleotide DNA

microarray analyses. Our study indicates significant upregulation of 238

and downregulation of 48 genes in six autistic brains compared to age

and gender matched healthy controls. We validated changes in >20

selected genes using real-time qPCR, with a success rate of 100%. The

obtained dataset, when analyzed by Gene Set Enrichment Analysis (GSEA) /

Biocarta functional classification, revealed statistically significant

enrichment in transcripts belonging to 30 different molecular cascades,

including the previously reported MET pathway. In a follow-up,

custom-designed pathway analysis a large subset of the upregulated genes

were identified as immune system-associated genes encoding either

signaling molecules, receptors, or transcription factors involved in

cell-cell communication, extracellular matrix maintenance and regulation

of cell growth or apoptosis. Many of the genes in this subgroup are

known to be directly or indirectly regulated by cytokines or modulating

cytokine production. We speculate that the observed transcriptome

changes are related to cytokine induction and may represent the reaction

of autistic brains to either environmental insults or to self-antigens

with enhanced and prolonged immune system activation. In follow-up

genetic association studies, we are testing if this altered immune

system response is rooted in genetic predisposition toward autism.

Disclosures: K.A. Garbett, None; P. Ebert, None; C. Lintas, None; K.

Mirnics, None; A.M. Persico, None.

Support: We wish to acknowledge the generosity of the donor families and

the help and support of the Autism Tissue Program

VUKC Startup Fund (KM)

R01 MH079299 (KM)

K02 MH070786 (KM)

MIUR-PRIN 2006058195 (AMP)