title: Up-Regulation of Oligodendrocyte Lineage Markers in the Cerebellum of Autistic Patients: Evidence from Network Analysis of Gene Expression.
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).
authors.affiliation: 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.
authors.forename: Fares
authors.initials: F
authors.lastname: Zeidán-Chuliá
authors.affiliation: 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.
authors.forename: Ben-Hur Neves
authors.initials: BN
authors.lastname: de Oliveira
authors.affiliation: Department of Biomedical Sciences, University of South Carolina School of Medicine - Greenville Campus, Greenville, SC, USA.
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Casanova
authors.affiliation: Department of Biomedical Sciences, University of South Carolina School of Medicine - Greenville Campus, Greenville, SC, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Casanova
authors.affiliation: Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry, Krasnoyarsk State Medical University, Krasnoyarsk, Russia.
authors.forename: Alla B
authors.initials: AB
authors.lastname: Salmina
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, UK.|IKERBASQUE, Basque Foundation for Science, Bilbao, Spain and Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa, Spain.|University of Nizhny Novgorod, Nizhny Novgorod, Russia.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D015415:Biomarkers
keywords: ASD; Connectivity; Development; Glia; Oligodendrocytes; Psychiatric disorders; White matter