Molecular Neurobiology

, Volume 53, Issue 6, pp 4019–4025 | Cite as

Up-Regulation of Oligodendrocyte Lineage Markers in the Cerebellum of Autistic Patients: Evidence from Network Analysis of Gene Expression

  • Fares Zeidán-Chuliá
  • Ben-Hur Neves de Oliveira
  • Manuel F. Casanova
  • Emily L. Casanova
  • Mami Noda
  • Alla B. Salmina
  • Alexei Verkhratsky
Article

Abstract

Autism is a neurodevelopmental disorder manifested by impaired social interaction, deficits in communication skills, restricted interests, and repetitive behaviors. In neurodevelopmental, neurodegenerative, and psychiatric disorders, glial cells undergo morphological, biochemical, and functional rearrangements, which are critical for neuronal development, neurotransmission, and synaptic connectivity. Cerebellar function is not limited to motor coordination but also contributes to cognition and may be affected in autism. Oligodendrocytes and specifically oligodendroglial precursors are highly susceptible to oxidative stress and excitotoxic insult. In the present study, we searched for evidence for developmental oligodendropathy in the context of autism by performing a network analysis of gene expression of cerebellar tissue. We created an in silico network model (OLIGO) showing the landscape of interactions between oligodendrocyte markers and demonstrated that more than 50 % (16 out of 30) of the genes within this model displayed significant changes of expression (corrected p value <0.05) in the cerebellum of autistic patients. In particular, we found up-regulation of OLIG2-, MBP-, OLIG1-, and MAG-specific oligodendrocyte markers. We postulate that aberrant expression of oligodendrocyte-specific genes, potentially related to changes in oligodendrogenesis, may contribute to abnormal cerebellar development, impaired myelination, and anomalous synaptic connectivity in autism spectrum disorders (ASD).

Keywords

ASD Psychiatric disorders White matter Glia Oligodendrocytes Connectivity Development 

Abbreviations

APP

amyloid protein precursor

ASD

autism spectrum disorders

CNS

central nervous system

FDR

false discovery rate

OL

oligodendrocyte

OPCs

oligodendroglial precursors.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Fares Zeidán-Chuliá
    • 1
  • Ben-Hur Neves de Oliveira
    • 1
  • Manuel F. Casanova
    • 2
  • Emily L. Casanova
    • 2
  • Mami Noda
    • 3
  • Alla B. Salmina
    • 4
  • Alexei Verkhratsky
    • 5
    • 6
    • 7
  1. 1.Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  2. 2.Department of Biomedical SciencesUniversity of South Carolina School of Medicine - Greenville CampusGreenvilleUSA
  3. 3.Laboratory of Pathophysiology, Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  4. 4.Department of Biochemistry, Medical, Pharmaceutical & Toxicological ChemistryKrasnoyarsk State Medical UniversityKrasnoyarskRussia
  5. 5.Faculty of Life SciencesThe University of ManchesterManchesterUK
  6. 6.IKERBASQUE, Basque Foundation for Science, Bilbao, Spain and Department of NeurosciencesUniversity of the Basque Country UPV/EHULeioaSpain
  7. 7.University of Nizhny NovgorodNizhny NovgorodRussia

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