title: Proteomic analysis of post mortem brain tissue from autism patients: evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity-related proteins.
abstract: BACKGROUND
  Autism is a neurodevelopmental disorder characterized by impaired language, communication and social skills. Although genetic studies have been carried out in this field, none of the genes identified have led to an explanation of the underlying causes. Here, we have investigated molecular alterations by proteomic profiling of post mortem brain samples from autism patients and controls. The analysis focussed on prefrontal cortex and cerebellum as previous studies have found that these two brain regions are structurally and functionally connected, and they have been implicated in autism.
  
  
  METHODS
  Post mortem prefrontal cortex and cerebellum samples from autism patients and matched controls were analysed using selected reaction monitoring mass spectrometry (SRM-MS). The main objective was to identify significantly altered proteins and biological pathways and to compare these across these two brain regions.
  
  
  RESULTS
  Targeted SRM-MS resulted in identification of altered levels of proteins related to myelination, synaptic vesicle regulation and energy metabolism. This showed decreased levels of the immature astrocyte marker vimentin in both brain regions, suggesting a decrease in astrocyte precursor cells. Also, decreased levels of proteins associated with myelination and increased synaptic and energy-related proteins were found in the prefrontal cortex, indicative of increased synaptic connectivity. Finally, opposite directional changes were found for myelination and synaptic proteins in the cerebellum.
  
  
  CONCLUSIONS
  These findings suggest altered structural and/or functional connectivity in the prefrontal cortex and cerebellum in autism patients, as shown by opposite effects on proteins involved in myelination and synaptic function. Further investigation of these findings could help to increase our understanding of the mechanisms underlying autism relating to brain connectivity, with the ultimate aim of facilitating novel therapeutic approaches.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, CB2 1QT Cambridge, UK.
authors.forename: Jantine Ac
authors.initials: JA
authors.lastname: Broek
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, CB2 1QT Cambridge, UK.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, CB2 1QT Cambridge, UK.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, CB2 1QT Cambridge, UK ; Department of Neuroscience, Erasmus Medical Centre, Dr. Molenwaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
keywords: Autism; Molecular profiling; Post mortem brain; Proteome; Selected reaction monitoring mass spectrometry; Synaptic regulation