Astrocytes: The Underlying Contributor to the Development of Autism
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Published
Jun 26, 2025
Abstract
Astrocytes, traditionally viewed as mere support cells in the central nervous system, have gained increasing recognition for their active roles in synaptic development, neurotransmission regulation, immune modulation, and neural circuitry refinement. Recent studies have implicated astrocyte dysfunction in a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). This hypothesis article explores the proposition that astrocytes are not peripheral participants but central contributors to the pathophysiology of ASD. By examining the developmental roles of astrocytes, their interactions with neurons and microglia, and how their dysfunction might influence core features of autism such as impaired social communication, repetitive behaviors, and sensory sensitivities, this paper aims to reframe our understanding of autism's neurobiological roots. Incorporating evidence from animal models, human postmortem studies, genetic analyses, and neuroimaging, this article calls for a paradigm shift in autism research, highlighting astrocytes as potential diagnostic biomarkers and therapeutic targets.
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Keywords
Astrocytes, Autism Spectrum Disorder, Neuronal Connections, Therapeutics, Neurobiology
References
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Vakilzadeh, G., Falcone, C., Dufour, B., Hong, T., Noctor, S. C., & Martínez-Cerdeño, V. (2022). Decreased number and increased activation state of astrocytes in gray and white matter of the prefrontal cortex in autism. Cerebral Cortex, 32(21), 4902–4912. DOI: https://doi.org/10.1093/cercor/bhab523
Wood, E. T., Cummings, K. K., Jung, J., Patterson, G., Okada, N., Guo, J., O’Neill, J., Dapretto, M., Bookheimer, S. Y., & Green, S. A. (2021). Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits. Translational Psychiatry, 11(1). DOI: https://doi.org/10.1038/s41398-020-01154-0
Xia, S., & Xu, H. (2022). Astrocytic gap junctions contribute to aberrant neuronal synchronization in a mouse model of MECP2 duplication syndrome. Neuroscience Bulletin, 38(6), 591–606. DOI: https://doi.org/10.1007/s12264-022-00824-x
Xiong, Y., Chen, J., & Li, Y. (2023). Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder. Frontiers in Neuroscience, 17. DOI: https://doi.org/10.3389/fnins.2023.1125428
Borroto-Escuela, D. O., Gonzalez-Cristo, E., Ochoa-Torres, V., Serra-Rojas, E. M., Ambrogini, P., Arroyo-García, L. E., & Fuxe, K. (2024). Understanding electrical and chemical transmission in the brain. Frontiers in Cellular Neuroscience, 18. DOI: https://doi.org/10.3389/fncel.2024.1398862
Cresto, N., Pillet, L., Billuart, P., & Rouach, N. (2019). Do astrocytes play a role in intellectual disabilities? Trends in Neurosciences, 42(8), 518–527. DOI: https://doi.org/10.1016/j.tins.2019.05.011
Ehinger, Y., Matagne, V., Cunin, V., Borloz, E., Seve, M., Bourgoin-Voillard, S., Borges-Correia, A., Villard, L., & Roux, J. (2021). Analysis of astroglial secretomic profile in the MECP2-Deficient male mouse model of RETT Syndrome. International Journal of Molecular Sciences, 22(9), 4316. DOI: https://doi.org/10.3390/ijms22094316
Gzielo, K., & Nikiforuk, A. (2021). Astroglia in autism spectrum disorder. International Journal of Molecular Sciences, 22(21), 11544. DOI: https://doi.org/10.3390/ijms222111544
Han, V. X., Jones, H. F., Patel, S., Mohammad, S. S., Hofer, M. J., Alshammery, S., Maple-Brown, E., Gold, W., Brilot, F., & Dale, R. C. (2021). Emerging evidence of Toll-like receptors as a putative pathway linking maternal inflammation and neurodevelopmental disorders in human offspring: A systematic review. Brain Behavior and Immunity, 99, 91–105. DOI: https://doi.org/10.1016/j.bbi.2021.09.009
Ilic, N., & Sarajlija, A. (2025). Neuroglial dysregulation in autism Spectrum Disorder: pathogenetic insights, genetic threads, and therapeutic horizons. Neuroglia, 6(1), 11. DOI: https://doi.org/10.3390/neuroglia6010011
Kowiański, P., Lietzau, G., Czuba, E., Waśkow, M., Steliga, A., & Moryś, J. (2017). BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity. Cellular and Molecular Neurobiology, 38(3), 579–593. DOI: https://doi.org/10.1007/s10571-017-0510-4
Lawrence, J. M., Schardien, K., Wigdahl, B., & Nonnemacher, M. R. (2023). Roles of neuropathology-associated reactive astrocytes: a systematic review. Acta Neuropathologica Communications, 11(1). DOI: https://doi.org/10.1186/s40478-023-01526-9
Liu, X., Ying, J., Wang, X., Zheng, Q., Zhao, T., Yoon, S., Yu, W., Yang, D., Fang, Y., & Hua, F. (2021). Astrocytes in neural circuits: key factors in synaptic regulation and potential targets for neurodevelopmental disorders. Frontiers in Molecular Neuroscience, 14. DOI: https://doi.org/10.3389/fnmol.2021.729273
Liu, Z., Mao, S., Hu, Y., Liu, F., & Shao, X. (2023). Hydrogel platform facilitating astrocytic differentiation through cell mechanosensing and YAP-mediated transcription. Materials Today Bio, 22, 100735. DOI: https://doi.org/10.1016/j.mtbio.2023.100735
Marinov, D., Eyubova, S., Toneva, A., Chamova, R., Braykova, R., Hadzhieva, S., & Pancheva, R. (2025). Linking Dietary patterns to autism severity and Developmental Outcomes: A correlational study using food frequency questionnaires; The Childhood Autism Rating Scale, second Edition; and Developmental Profile 3. Biomedicines, 13(5), 1178. DOI: https://doi.org/10.3390/biomedicines13051178
Matta, S. M., Hill-Yardin, E. L., & Crack, P. J. (2019). The influence of neuroinflammation in Autism Spectrum Disorder. Brain Behavior and Immunity, 79, 75–90. DOI: https://doi.org/10.1016/j.bbi.2019.04.037
Pereira, A. C., Leonard, A., Velthuis, H., Wong, N. M. L., Ponteduro, F. M., Dimitrov, M., Ellis, C. L., Kowalewski, L., Lythgoe, D. J., Rotaru, D., Edden, R. a. E., Ivin, G., Pretzsch, C. M., Daly, E., Murphy, D. G. M., & McAlonan, G. M. (2024). Frontal and occipital brain glutathione levels are unchanged in autistic adults. PLoS ONE, 19(8), e0308792. DOI: https://doi.org/10.1371/journal.pone.0308792
Rabindran, Madanagopal, D., & Shasidaran. (2020). Sensory Processing Dysfunction in Children with Autism Spectrum Disorder. Scholars Journal of Applied Medical Sciences, 8(9), 2085–2089. DOI: https://doi.org/10.36347/sjams.2020.v08i09.021
Ramya, V., Shyam, K. P., Kowsalya, E., Balavigneswaran, C. K., & Kadalmani, B. (2022). Dual roles of coconut oil and its major component lauric acid on Redox Nexus: focus on cytoprotection and cancer cell death. Frontiers in Neuroscience, 16. DOI: https://doi.org/10.3389/fnins.2022.833630
Sauer, A. K., Stanton, J. E., Hans, S., & Grabrucker, A. M. (2021). Autism Spectrum Disorders: Etiology and Pathology. In Exon Publications eBooks (pp. 1–16). DOI: https://doi.org/10.36255/exonpublications.autismspectrumdisorders.2021.etiology
Scimemi, A., Meabon, J. S., Woltjer, R. L., Sullivan, J. M., Diamond, J. S., & Cook, D. G. (2013). Amyloid-Β1–42Slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1. Journal of Neuroscience, 33(12), 5312–5318. DOI: https://doi.org/10.1523/jneurosci.5274-12.2013
Vakilzadeh, G., Falcone, C., Dufour, B., Hong, T., Noctor, S. C., & Martínez-Cerdeño, V. (2022). Decreased number and increased activation state of astrocytes in gray and white matter of the prefrontal cortex in autism. Cerebral Cortex, 32(21), 4902–4912. DOI: https://doi.org/10.1093/cercor/bhab523
Wood, E. T., Cummings, K. K., Jung, J., Patterson, G., Okada, N., Guo, J., O’Neill, J., Dapretto, M., Bookheimer, S. Y., & Green, S. A. (2021). Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits. Translational Psychiatry, 11(1). DOI: https://doi.org/10.1038/s41398-020-01154-0
Xia, S., & Xu, H. (2022). Astrocytic gap junctions contribute to aberrant neuronal synchronization in a mouse model of MECP2 duplication syndrome. Neuroscience Bulletin, 38(6), 591–606. DOI: https://doi.org/10.1007/s12264-022-00824-x
Xiong, Y., Chen, J., & Li, Y. (2023). Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder. Frontiers in Neuroscience, 17. DOI: https://doi.org/10.3389/fnins.2023.1125428
How to Cite
Agustina, P. (2025). Astrocytes: The Underlying Contributor to the Development of Autism. Science Insights, 46(6), 1857–1861. https://doi.org/10.15354/si.25.hp010
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Section
Hypothesis
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