Proteomic Explorations of Autism Brain - Part 1

ABSTRACT: Autism Spectrum Disorder (ASD) is a group of common neurodevelopmental conditions with impairments in socialization, communication and restricted behaviors. Only a minority of ASD cases are determined to have a definitive etiology and the pathogenesis of most ASD remains poorly understood. In this study, we made use of the power of proteomics, heretofore little utilized in the study of the biology of ASD, and analyzed the proteomes of two brain regions, Brodmann area 19 (BA19) and posterior inferior cerebellum (CB), from 9 idiopathic ASD cases/9 matched controls by label-free HPLC-tandem mass spectrometry (MS) and validated the differentially expressed protein findings with selected-reaction monitoring MS. The data revealed marked differences between ASD and control brain proteomes for both brain regions, with numerous differentially expressed proteins, although the proteomic difference between brain regions was not attenuated in ASD brain. Bioinformatic analyses based on the differentially expressed proteins highlighted multiple canonical pathways and protein-protein interaction networks that are implicated in the differential biology of ASD vs. controls. Canonical pathways involving glutamate receptor signaling and RXR activation were enriched for both BA19 and CB; others such as cell-cell junction signaling and fatty acid oxidation were enriched for BA19 and CB, respectively. Network analysis revealed a protein interaction network related to synaptic biology in BA19 and another involving cytoskeletal/vesicular functions in CB. Upstream regulator analysis for both regions revealed multiple neurodegeneration-associated proteins. The finding of several shared canonical pathways and upstream regulators for both regions underscores likely common ASD pathophysiology that has distinctive regional expression.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Electrically Active Cell

DISEASE(S): Neurodevelopmental Abnormality

SUBMITTER: Kathleen Lundberg  

LAB HEAD: Marvin Natowicz

PROVIDER: PXD012755 | Pride | 2019-09-16

REPOSITORIES: Pride