scholarly journals Microglial ASD-related genes are involved in oligodendrocyte differentiation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuta Takanezawa ◽  
Shogo Tanabe ◽  
Daiki Kato ◽  
Rie Ozeki ◽  
Masayo Komoda ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Differentiation ◽  
Spectrum Disorders ◽  
Oligodendrocyte Precursor ◽  
Oligodendrocyte Development ◽  
Igf1 Expression ◽  
Phagocytosis Activity

AbstractAutism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial functions and microglia-mediated brain development remains unclear. In this study, we investigated the role of microglial Chd8 and Tsc2 in cytokine expression, phagocytosis activity, and neuro/gliogenesis from neural stem cells (NSCs) in vitro. Chd8 or Tsc2 knockdown in microglia reduced insulin-like growth factor-1(Igf1) expression under lipopolysaccharide (LPS) stimulation. In addition, phagocytosis activity was inhibited by Tsc2 deficiency, microglia-mediated oligodendrocyte development was inhibited, in particular, the differentiation of oligodendrocyte precursor cells to oligodendrocytes was prevented by Chd8 or Tsc2 deficiency. These results suggest that ASD-related gene expression in microglia is involved in oligodendrocyte differentiation, which may contribute to the white matter pathology relating to ASD.

A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1097-1108 ◽  
Author(s):  
B.A. Barres ◽  
M.A. Lazar ◽  
M.C. Raff
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Precursor Cells ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Differentiation ◽  
Cell Divisions ◽  
Oligodendrocyte Precursor ◽  
Oligodendrocyte Development

The timing of oligodendrocyte differentiation is thought to depend on an intrinsic clock in oligodendrocyte precursor cells that counts time or cell divisions and limits precursor cell proliferation. We show here that this clock mechanism can be separated into a counting component and an effector component that stops cell proliferation: whereas the counting mechanism is driven by mitogens that activate cell-surface receptors, the effector mechanism depends on hydrophobic signals that activate intracellular receptors, such as thyroid hormones, glucocorticoids and retinoic acid. When purified oligodendrocyte precursor cells are cultured at clonal density in serum-free medium in the presence of mitogens but in the absence of these hydrophobic signals, the cells divide indefinitely and do not differentiate into postmitotic oligodendrocytes. In the absence of mitogens, the precursor cells stop dividing and differentiate prematurely into oligodendrocytes even in the absence of these hydrophobic signals, indicating that these signals are not required for differentiation. The levels of these signals in vivo may normally regulate the timing of oligodendrocyte differentiation, as the maximum number of precursor cell divisions in culture depends on the concentration of such signals and injections of thyroid hormone into newborn rats accelerates oligodendrocyte development. As thyroid hormone, glucocorticoids and retinoic acid have been shown to promote the differentiation of many types of vertebrate cells, it is possible that they help coordinate the timing of differentiation by signalling clocks in precursor cells throughout a developing animal.

Critical role of dysfunctional mitochondria and defective mitophagy in autism spectrum disorders

2021 ◽  
Vol 168 ◽  
pp. 138-145
Author(s):  
Yuan-Mei Wang ◽  
Ming-Yue Qiu ◽  
Qing Liu ◽  
Huang Tang ◽  
Hong-Feng Gu
Keyword(s):  
Autism Spectrum Disorders ◽  
Critical Role ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals Mutation analysis of the NRXN1 gene in autism spectrum disorders

2016 ◽  
Vol 19 (2) ◽  
pp. 17-22 ◽  
Author(s):  
H Onay ◽  
D Kacamak ◽  
AN Kavasoglu ◽  
B Akgun ◽  
M Yalcinli ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum Disorders ◽  
Children And Adolescents ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Syndromic Autism ◽  
Spectrum Disorders ◽  
Strong Candidate ◽  
Reduced Penetrance

AbstractThe aim of this study was to identify the sequence mutations in the Neurexin 1 (NRXN1) gene that has been considered as one of the strong candidate genes. A total of 30 children and adolescents (aged 3-18) with non syndromic autism were enrolled this study. Sequencing of the coding exons and the exon-intron boundaries of the NRXN1 gene was performed. Two known mutations were described in two different cases. Heterozygous S14L was determined in one patient and heterozygous L748I was determined in another patient. The S14L and L748I mutations have been described in the patients with autism before. Both of these mutations were inherited from their father. In this study, two of 30 (6.7%) autism spectrum disorder (ASD) patients carrying NRXN1 gene mutations were detected. It indicates that variants in the NRXN1 gene might confer a risk of developing nonsyndromic ASD. However, due to the reduced penetrance in the gene, the causal role of the NRXN1 gene mutations must be evaluated carefully in all cases.

scholarly journals TCF12 controls oligodendroglial cell proliferation and regulates signaling pathways conserved in gliomas

2021 ◽  
Author(s):  
Sofia Archontidi ◽  
Corentine Marie ◽  
Beata Gyorgy ◽  
Justine Guegan ◽  
Marc Sanson ◽  
...  
Keyword(s):  
Biological Processes ◽  
Oligodendrocyte Differentiation ◽  
Gene Encoding ◽  
Genome Wide ◽  
Diffuse Gliomas ◽  
Mrna And Protein Expression ◽  
Oligodendrocyte Precursor ◽  
Oligodendrocyte Development ◽  
Chromatin Profiling

Diffuse gliomas are primary brain tumors originating from the transformation of glial cells. In particular, oligodendrocyte precursor cells constitute the major tumor-amplifying population in the gliomagenic process. We previously identified the TCF12 gene, encoding a transcription factor of the E protein family, as being recurrently mutated in oligodendrogliomas. In this study, we sought to understand the function of TCF12 in oligodendroglial cells, the glioma lineage of origin. We first describe TCF12 mRNA and protein expression pattern in oligodendroglial development in the mouse brain. Second, by TCF12 genome wide chromatin profiling in oligodendroglial cells, we show that TCF12 binds active promoters of genes involved in proliferation, translation/ribosomes, and pathways involved in oligodendrocyte development and cancer. Finally, we perform OPC-specific Tcf12 inactivation in vivo and demonstrate by immunofluorescence and transcriptomic analyses that TCF12 is transiently required for OPC proliferation but dispensable for oligodendrocyte differentiation. We further show that Tcf12 inactivation results in deregulation of biological processes that are also altered in oligodendrogliomas. Together, our data suggest that TCF12 directly regulates transcriptional programs in oligodendroglia development that are relevant in a glioma context.

scholarly journals The role of genetic factors and pre- and peri-natal influences in the etiology of autism spectrum disorders – indications for genetic referral

2016 ◽  
Vol 50 (3) ◽  
pp. 543-554 ◽  
Author(s):  
Filip Rybakowski ◽  
Izabela Chojnicka ◽  
Piotr Dziechciarz ◽  
Andrea Horvath ◽  
Małgorzata Janas-Kozik ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Genetic Factors ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals Preparation for Independent Life of People with ASD and Other Developmental Disorders in The Autonomous Noncommercial Organization «Adain Lo» (ANO «Adain Lo»).

2018 ◽  
Vol 16 (1) ◽  
pp. 29-35
Author(s):  
A.A. Ginsburg ◽  
M.E. Gitshabash ◽  
Ya.L. Ivanova
Keyword(s):  
Developmental Disorders ◽  
Autism Spectrum ◽  
Adults With Autism ◽  
Saint Petersburg ◽  
Independent Life ◽  
Spectrum Disorders ◽  
Self Service ◽  
Role Of Parents ◽  
Commercial Organization

The problems of preparation of children and adults with autism spectrum disorders and other developmental disabilities for independent life, modern ways of development of their independence are considered. The role of parents in this process and parent-specialist interaction are stressed. The techniques of tutor support, parents and other specialists are described. Presented techniques are realized in autonomous non-commercial organization «Adain Lo» (Saint-Petersburg) and aimed for maintenance of independent life, self-service, game, communication and education of people with special needs.

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