Update on atypicalities of central nervous system in autism spectrum disorder

• Main Authors: Ismail, J. (Author), Jayusman, P.A (Author), Mohamed, I.N (Author), Nor, N.K (Author), Shuid, A.N (Author), Shuid, N. (Author)
• Format: Article
• Language: English
• Published: MDPI AG, 2020
• Subjects: 4 aminobutyric acid receptor; adenosine triphosphate; alanine; amygdala; anterior cingulate; asparagine; Asperger syndrome; autism; Autism; Autism Diagnostic Questionnaire; Autism spectrum disorder; behavior change; biopterin; Brain; brain function; central nervous system; Central nervous system; cerebellum nucleus; cerebrospinal fluid examination; chemokine; creatine kinase; creatinine; cytokine; disorders of mitochondrial functions; emotional disorder; enzyme linked immunosorbent assay; functional magnetic resonance imaging; gamma interferon; gas chromatography; glia cell; glutamate receptor; glutamic acid; granulocyte macrophage colony stimulating factor; high performance liquid chromatography; hippocampus; human; immune dysregulation; innate immunity; intelligence quotient; interleukin 10; interleukin 12; interleukin 13; interleukin 1beta; interleukin 6; interleukin 8; lysine; metalloproteinase; mild cognitive impairment; monocyte chemotactic protein 1; nerve cell plasticity; nervous system development; nervous system inflammation; neurologic disease; neurotransmission; neurotransmitter release; perception; phenylalanine; polymerase chain reaction; proton nuclear magnetic resonance; questionnaire; quinolinic acid; Review; signal transduction; social cognition; social Responsiveness Scale; spectrophotometry; steroid hormone; target of rapamycin kinase; thrombocyte poor plasma; time of flight mass spectrometry; transforming growth factor beta1; tumor necrosis factor; tyrosine; unindexed drug; Western blotting; white matter
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 20763425 (ISSN)
• ISSN: 20763425 (ISSN)
• DOI: 10.3390/brainsci10050309

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.