Immune transcript disturbances in temporal cortex of autistic brains

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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)

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