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Mol Neurobiol. 2016 Aug;53(6):4019-4025. doi: 10.1007/s12035-015-9351-7. Epub 2015 Jul 21.

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

Author information

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. fzchulia.biomed@gmail.com.
2
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.
3
Department of Biomedical Sciences, University of South Carolina School of Medicine - Greenville Campus, Greenville, SC, USA.
4
Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
5
Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry, Krasnoyarsk State Medical University, Krasnoyarsk, Russia.
6
Faculty of Life Sciences, The University of Manchester, Manchester, UK.
7
IKERBASQUE, Basque Foundation for Science, Bilbao, Spain and Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa, Spain.
8
University of Nizhny Novgorod, Nizhny Novgorod, Russia.

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; Connectivity; Development; Glia; Oligodendrocytes; Psychiatric disorders; White matter

PMID:
26189831
DOI:
10.1007/s12035-015-9351-7
[Indexed for MEDLINE]

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