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

• Published in: Molecular neurobiology Vol. 53; no. 6; pp. 4019 - 4025
• Main Authors: Zeidán-Chuliá, Fares, de Oliveira, Ben-Hur Neves, Casanova, Manuel F., Casanova, Emily L., Noda, Mami, Salmina, Alla B., Verkhratsky, Alexei
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2016; Springer Nature B.V
• Subjects: Analysis; Autism; Autistic Disorder - genetics; Biomarkers; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Lineage - genetics; Cerebellum - metabolism; Cerebellum - pathology; Gene expression; Gene Expression Profiling; Gene Regulatory Networks; Humans; Neurobiology; Neurology; Neurosciences; Oligodendroglia - metabolism; Oligodendroglia - pathology; Up-Regulation - genetics; ASD; Oligodendrocytes; Development; Connectivity; Glia; Psychiatric disorders; White matter
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-015-9351-7

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).