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

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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).

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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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Acknowledgements

FZC holds a PNPD postdoctoral position (Programa de Pós Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul) funded by CAPES. AV was supported in part by the grant (agreement from 27 August 2013 No. 02.B.49.21.0003) between The Ministry of Education and Science of the Russian Federation and Lobachevsky State University of Nizhny Novgorod and by the grant of the Russian Scientific Foundation No.14-15-00633.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600-anexo-Bairro Santana, 90035-003, Porto Alegre, RS, Brazil

    Fares Zeidán-Chuliá & Ben-Hur Neves de Oliveira

  2. Department of Biomedical Sciences, University of South Carolina School of Medicine - Greenville Campus, Greenville, SC, USA

    Manuel F. Casanova & Emily L. Casanova

  3. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

    Mami Noda

  4. Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry, Krasnoyarsk State Medical University, Krasnoyarsk, Russia

    Alla B. Salmina

  5. Faculty of Life Sciences, The University of Manchester, Manchester, UK

    Alexei Verkhratsky

  6. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain and Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa, Spain

    Alexei Verkhratsky

  7. University of Nizhny Novgorod, Nizhny Novgorod, Russia

    Alexei Verkhratsky

Authors
  1. Fares Zeidán-Chuliá
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  2. Ben-Hur Neves de Oliveira
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  3. Manuel F. Casanova
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  4. Emily L. Casanova
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  5. Mami Noda
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  6. Alla B. Salmina
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  7. Alexei Verkhratsky
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Correspondence to Fares Zeidán-Chuliá.

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Zeidán-Chuliá, F., de Oliveira, BH.N., Casanova, M.F. et al. Up-Regulation of Oligodendrocyte Lineage Markers in the Cerebellum of Autistic Patients: Evidence from Network Analysis of Gene Expression. Mol Neurobiol 53, 4019–4025 (2016). https://doi.org/10.1007/s12035-015-9351-7

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  • DOI: https://doi.org/10.1007/s12035-015-9351-7

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