ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
This article is part of the Research TopicThe developing brain: pathway disruptions contributing to Autism and Intellectual DisabilitiesView all articles
Astrocytic gatekeeping of neural circuitry and synaptic balance in an autism mouse model: Mechanistic Insights Beyond Gryllus bimaculatus extract-derived Therapy
Provisionally accepted
- Jeonbuk National University, Jeonju, Republic of Korea
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Background Autism spectrum disorder (ASD) is characterized by impaired synaptic development and disrupted excitation/inhibition (E/I) balance. While neuronal mechanisms have been extensively studied, accumulating evidence indicates that glial cells—particularly astrocytes—play a crucial role in maintaining synaptic homeostasis and regulating neurotransmission during brain development. However, the functional contribution of astrocytes to ASD pathogenesis remains insufficiently defined. Methods This study aimed to explore astrocyte-mediated regulation of E/I balance in ASD using Gryllus bimaculatus (Gb) extract as a neuroprotective biological probe. A valproic acid (VPA)-induced ASD mouse model was established, and glial-neuronal interactions were assessed through analyses of neural progenitor cells, primary cortical neurons, astrocytes, and neuron-astrocyte co-cultures. Results Gb extract reversed VPA-induced alterations in neural progenitor proliferation and differentiation and restored expression of key synaptic proteins (neuroligins, neurexin, synaptophysin). Notably, astrocyte-specific markers (GFAP, EAAT1/2) and E/I-related transporters (vGluT1, VGAT, GABA R1α, NMDA R1) were dysregulated in the ASD model and normalized by Gb treatment. Co-culture experiments demonstrated that astrocytes from VPA-treated animals, rather than neurons alone, were primarily responsible for E/I imbalance and synaptic abnormalities. Gb extract acted as a modulator of astrocytic function, restoring synaptic integrity and neurodevelopmental stability. Conclusion Our findings underscore the pivotal role of astrocytes in the development and modulation of ASD-related synaptic pathology. Gb extract served as a valuable biological tool to reveal glial contributions to synaptic regulation and E/I balance. These insights support targeting astrocytic pathways with Gb extract as a novel therapeutic strategy for ASD.
Keywords: Astrocyte dysfunction, Autism Spectrum Disorder, excitation/inhibition balance, Glial-neuronal interaction, Natural extract, Synaptic regulation
Received: 01 Aug 2025; Accepted: 06 Nov 2025.
Copyright: © 2025 Lee, Tran and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sook-Jeong Lee, sj@jbnu.ac.kr
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