Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and repetitive behavior. Early indicators are that glial cells—astrocytes, microglia, and oligodendrocytes—are at the center of the etiology and pathogenesis of ASD. A systematic review of literature studies examining glial cell pathology in ASD was conducted. Peer-reviewed literature on astrocyte function, microglial phenotypes, oligodendrocyte-mediated connectivity, and molecular pathways of neurotransmission and neuroinflammation was searched in databases. Astrocytes, playing a crucial role in synaptogenesis and neurotransmitter modulation, exhibit disrupted calcium signaling and increased IL-6 expression in ASD, potentially leading to neuroinflammation and synaptic injury. Microglia, maintaining synaptic homeostasis, become pro-inflammatory (M1) in ASD, which produces cytokines that destroy neurons. Disrupted oligodendrocyte function is linked to aberrant myelination and disrupted neural connectivity. Molecular mechanisms underlie dysregulated activation of toll-like receptors, cytokine signaling, oxidative stress, and dysregulation of glutamate/GABA metabolism. Environmental toxins like chlorpyrifos aggravate excitatory signaling and glial dysfunction. Most of the features of ASD are caused by these glial disorders. Interventions to correct glial dysfunction—e.g., anti-inflammatory medication (e.g., minocycline, ibudilast), gene therapy, and stem cell therapy—are investigated for their potential to restore glia to normal and diminish ASD symptoms. Understanding glial-neuronal communication mechanisms and their role in neuroinflammation offers a hopeful future for accurate, target-specific treatment. Advances in the elucidation of these processes will foretell an enormous increase in therapeutic efficacy and quality of life for individuals with ASD.
Kaur et al. (2026) studied this question.