AI Article Synopsis
- Autism spectrum disorder (ASD) is associated with social and cognitive difficulties, and certain genetic mutations, particularly in the Shank3 gene, are linked to specific cases of monogenic ASD.
- Research using the InsG3680 mouse model shows that Shank3 plays an important role in the functioning of oligodendrocytes (cells that support myelin in the brain) and affects their development negatively when mutated.
- The study found that InsG3680 mice had significant issues with myelin formation and motor skills, showing that problems with Shank3 and oligodendrocytes may contribute to the neurological aspects of ASD.
Article Abstract
Autism spectrum disorder (ASD) is characterized by social and neurocognitive impairments, with mutations of the gene being prominent in patients with monogenic ASD. Using the InsG3680 mouse model with a mutation seen in humans, we revealed an unknown role for Shank3 in postsynaptic oligodendrocyte (OL) features, similar to its role in neurons. This was shown by impaired molecular and physiological glutamatergic traits of InsG3680-derived primary OL cultures. In vivo, InsG3680 mice exhibit significant reductions in the expression of key myelination-related transcripts and proteins, along with deficits in myelin ultrastructure, white matter, axonal conductivity, and motor skills. Last, we observed significant impairments, with clinical relevance, in induced pluripotent stem cell-derived OLs from a patient with the InsG3680 mutation. Together, our study provides insight into Shank3's role in OLs and reveals a mechanism of the crucial connection of myelination to ASD pathology.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468907 | PMC |
| http://dx.doi.org/10.1126/sciadv.adl4573 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Role of Glial Cells in Autism Spectrum Disorder: Molecular Mechanisms and Therapeutic Approaches.
CNS Neurol Disord Drug Targets
January 2025
Department of Pharmacy, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad (UP)-244001, India.
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Emerging evidence highlights the significant role of glial cells, particularly astrocytes and microglia, in the pathophysiology of ASD. Glial cells are crucial for maintaining homeostasis, modulating synaptic function, and responding to neural injury.
View Article and Find Full Text PDFTargeting S100A9 attenuates social dysfunction by modulating neuroinflammation and myelination in a mouse model of autism.
Pharmacol Res
January 2025
Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing 40038, China. Electronic address:
Growing evidence supports a role for dysregulated neuroinflammation in autism. However, the underlying mechanisms of microglia-evoked neuroinflammation in the development of autistic phenotypes have not been elucidated. This study aimed to investigate the role and underlying mechanisms of microglial S100 calcium-binding protein A9 (S100A9) in autistic phenotypes.
View Article and Find Full Text PDF["Pseudoneurotransmission" and gut microbiome - brain communication in neuropsychiatric disorders].
Psychiatriki
December 2024
Democritus University of Thrace, Alexandroupolis, Greece.
The gut microbiome, which comprises symbiotic bacteria colonizing the human digestive tract, undergoes dynamic changes during the lifespan, as evidenced by the fact that the number of species and the diversity of their composition decrease significantly with age. The aim of this review is to illuminate bilateral neuroimmunological pathways that determine the role of gut microbiome dysbiosis, not only as a cause but also as a byproduct of many neurodegenerative diseases of the CNS, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but also in the frame of several behavioral and psychiatric pathological conditions such as depressive and anxiety disorders, schizophrenia, and autism spectrum disorder (ASD). Dysbiosis, in particular, reveals a model of "deceptive" mimicry of host molecules that might cause abnormal folding ("misfolding") and pathological aggregation of Aβ-peptide, leading to its dispersion through the gut-brain axis, precipitating microglia cell activation.
View Article and Find Full Text PDFAssociation of Gene Polymorphic Variants with the Clinical Phenotype of Autism Spectrum Disorder.
J Clin Med
November 2024
Department of Biochemistry and Medical Genetics, School of Health Sciences in Katowice, Medical University of Silesia in Katowice, Medykow Street 18, 40-752 Katowice, Poland.
: The gene encodes chromodomain helicase DNA-binding protein 8 (CHD8), which is a transcriptional regulator involved in neuron development, myelination, and synaptogenesis. Some gene mutations lead to neurodevelopmental syndromes with core symptoms of autism. The aim of this study was to perform an analysis of the family-based association of gene polymorphisms with the occurrence and clinical phenotype of autism spectrum disorder (ASD).
View Article and Find Full Text PDFInvolvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder.
BMC Med
November 2024
Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China.
Background: Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear.
Methods: The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!