Abstract
Autism Spectrum Disorder (ASD) is an early neurodevelopmental disorder that involves deficits in interpersonal communication, social interaction, and repetitive behaviors. Although ASD pathophysiology is still uncertain, alterations in the abnormal development of the frontal lobe, limbic areas, and putamen generate an imbalance between inhibition and excitation of neuronal activity. Interestingly, recent findings suggest that a disruption in neuronal connectivity is associated with neural alterations in white matter production and myelination in diverse brain regions of patients with ASD. This review is aimed to summarize the most recent evidence that supports the notion that abnormalities in the oligodendrocyte generation and axonal myelination in specific brain regions are involved in the pathophysiology of ASD. Fundamental molecular mediators of these pathological processes are also examined. Determining the role of alterations in oligodendrogenesis and myelination is a fundamental step to understand the pathophysiology of ASD and identify possible therapeutic targets.
Highlights
In 1943, Kanner described the first symptoms of Autism Spectrum Disorder (ASD) as an innate disturbance of affective contact
We described the general pathogenesis and neuroanatomical changes found in several regions of the ASD brain and many of these areas correspond to white matter regions
Disruption of phosphatase and tensin homolog (PTEN) activity by increasing Akt phosphorylation at Ser437 produces severe changes in the population of oligodendrocyte precursor cells (OPCs) and in the genes and proteins involved in myelination (MBP, PLP, and myelin-associated glycoprotein-MAG), which induces social deficits that mimic some symptoms of ASD [156], such as increased anxiety and reduced social interest [153]
Summary
In 1943, Kanner described the first symptoms of Autism Spectrum Disorder (ASD) as an innate disturbance of affective contact. Pathological changes in the cytoarchitecture of white matter in all brain lobes [30] and altered myelination rate in corpus callosum [1,37] may explain the dysfunctional connectivity found in medial parietal and temporoparietal regions [16] These structural disruptions have been correlated to parental age [38] and may explain the severity of stereotypes and deficits in social interaction [31]. Taken together, these reports suggest that some pathological changes observed in the white matter may explain the abnormal brain development related to ASD
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call