ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Cellular and Molecular Mechanisms of Brain-aging
This article is part of the Research TopicThe Role of Neurotransmitters: From Normal Aging to Age-Related Diseases, Volume IIView all 4 articles
A transcriptomic resource for glial GABA-associated ASH neuronal aging and candidate pathways
Provisionally accepted
- Zhejiang University, Hangzhou, China
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Neuronal aging is tightly linked to neurodegeneration, with dysregulation of GABA (gamma-aminobutyric acid), the primary inhibitory neurotransmitter, contributing to age-associated neuronal impairment. Our prior work demonstrated that restoring UNC-25 (glutamic acid decarboxylase, GAD), the key GABA-synthesizing enzyme, in Caenorhabditis elegans AMsh glia mitigates age-related neurodegeneration. Here, we present transcriptomic data of glutamatergic ASH sensory neurons (a critical target of aging-related neurodegeneration) from three aging groups: wild-type worms, unc-25 (GABA-deficient) mutants, and unc-25 mutants with AMsh glia-specific UNC-25 rescue. This study aims to provide a transcriptomic resource and identify potential pathways associated with glial GABA modulation during neuronal aging. Transcriptomic analyses revealed distinct transcriptional profiles across groups. Notably, the Hedgehog signaling pathway and its transcriptional effector TRA-1/GLI , the C. elegans GLI ortholog, were specifically upregulated in the glial rescue group, while the neuroprotective transcription factor HSF-1 was downregulated, suggesting these pathways as potential mediators of glial GABA-associated neuroprotection. We also provide transcriptomic comparisons between AMsh glia and ASH neurons in young worms, laying a foundation for understanding glia-neuron crosstalk. This work establishes a valuable transcriptomic resource for glial GABA-associated ASH neuronal aging and identifies candidate pathways, offering critical molecular insights to dissect age-related neurodegeneration mechanisms and inform potential therapeutic targets.
Keywords: C. elegans, GABA, glia-neuronal interaction, neuronal aging, Transcriptomic analyses
Received: 01 Aug 2025; Accepted: 23 Jan 2026.
Copyright: © 2026 Al-Sheikh, Cheng, Abdulsalam, He, Chen, Zhan, Kang and ZHANG. 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: Lijun Kang
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