Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models.

Autor:	Vacharasin JM; Department of Biological Sciences, and Center for Childhood Neurotherapeutics, Univ. of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA.; Department of Biological Sciences, Francis Marion University, 4822 East Palmetto Street, Florence, S.C. 29506, USA., Ward JA; Department of Molecular Biology, Cell Biology, & Biochemistry, Brown University, 185 Meeting Street, Providence, RI 02912, USA.; Center for Translational Neuroscience, Carney Institute of Brain Science, Brown University, 70 Ship Street, Providence, RI 02903, USA., McCord MM; Department of Biological Sciences, and Center for Childhood Neurotherapeutics, Univ. of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA., Cox K; Department of Biological Sciences, and Center for Childhood Neurotherapeutics, Univ. of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA., Imitola J; Laboratory of Neural Stem Cells and Functional Neurogenetics, UConn Health, Departments of Neuroscience, Neurology, Genetics and Genome Sciences, UConn Health, 263 Farmington Avenue, Farmington, CT 06030-5357, USA., Lizarraga SB; Department of Molecular Biology, Cell Biology, & Biochemistry, Brown University, 185 Meeting Street, Providence, RI 02912, USA.; Center for Translational Neuroscience, Carney Institute of Brain Science, Brown University, 70 Ship Street, Providence, RI 02903, USA.
Jazyk:	angličtina
Zdroj:	Oxford open neuroscience [Oxf Open Neurosci] 2024 Feb 22; Vol. 3, pp. kvae003. Date of Electronic Publication: 2024 Feb 22 (Print Publication: 2024).
DOI:	10.1093/oons/kvae003
Abstrakt:	Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed in males than in females. Core features of ASD are impaired social interactions, repetitive behaviors and deficits in verbal communication. ASD is a highly heterogeneous and heritable disorder, yet its underlying genetic causes account only for up to 80% of the cases. Hence, a subset of ASD cases could be influenced by environmental risk factors. Maternal immune activation (MIA) is a response to inflammation during pregnancy, which can lead to increased inflammatory signals to the fetus. Inflammatory signals can cross the placenta and blood brain barriers affecting fetal brain development. Epidemiological and animal studies suggest that MIA could contribute to ASD etiology. However, human mechanistic studies have been hindered by a lack of experimental systems that could replicate the impact of MIA during fetal development. Therefore, mechanisms altered by inflammation during human pre-natal brain development, and that could underlie ASD pathogenesis have been largely understudied. The advent of human cellular models with induced pluripotent stem cell (iPSC) and organoid technology is closing this gap in knowledge by providing both access to molecular manipulations and culturing capability of tissue that would be otherwise inaccessible. We present an overview of multiple levels of evidence from clinical, epidemiological, and cellular studies that provide a potential link between higher ASD risk and inflammation. More importantly, we discuss how stem cell-derived models may constitute an ideal experimental system to mechanistically interrogate the effect of inflammation during the early stages of brain development. Competing Interests: The authors declare no conflict of interests. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu