Enteric Glial Cells in Brain Aging and Neurodegeneration: From Historical Roots to Neuroinflammatory Paradigms in the Gut-Brain Axis

Enteric glial cells (EGCs) are increasingly recognized as vital communicators between the gut and the brain. Once thought to play only a supportive role in gastrointestinal physiology, EGCs are now understood as dynamic players that help regulate both gut homeostasis and central nervous system (CNS) function. Over the past decade, enteric neuroscience has revealed that these cells are key mediators of bidirectional signaling within the gut brain axis. Emerging evidence suggests that EGC dysfunction can contribute to the chronic neuroinflammatory processes associated with aging and neurodegenerative diseases. Despite their peripheral location, EGCs influence systemic inflammation through cytokine signaling, oxidative stress modulation, and effects on intestinal barrier integrity. Major open questions include how age related changes in EGC phenotype and activity affect gut brain communication and whether pharmacological modulation of these cells might delay neuronal decline in disorders such as Parkinson’s and Alzheimer’s diseases. While recent work using multi omic, pharmacological, and translational models has advanced our understanding of EGC biology, important gaps remain in defining their precise mechanisms in the onset and progression of neuroinflammation across the lifespan. Bridging these gaps calls for an integrated approach that connects historical insights with modern molecular and pharmacological research.This Research Topic aims to advance understanding of how enteric glial networks shape the inflammatory and degenerative trajectories of the aging brain. It seeks to consolidate recent advances linking EGC biology to neuroinflammatory paradigms along the gut-brain axis, explore pharmacological interventions that target EGC-mediated signaling, and address fundamental questions regarding their translational potential. Specifically, it encourages studies that clarify how modulating EGC activity can influence neurodegenerative disease progression and identify novel therapeutic strategies rooted in glial pharmacology. By uniting researchers across neuroinflammation, glial biology, and neuropharmacology, this Topic will illuminate the complex interdependence between peripheral gastrointestinal networks and central neural aging.To gather further insights into the intersections of enteric glial biology, neuropharmacology, and aging neuroscience, we welcome articles that address, but are not limited to, the following themes:- Age-related changes in EGC morphology, function, and signaling cascades- Pharmacological modulation of EGC-mediated neuroinflammation and gut-brain communication- Mechanisms linking gut barrier integrity, microbiota alterations, and systemic inflammation to CNS neurodegeneration- EGC contributions to disease progression in Parkinson’s disease, Alzheimer’s disease, and related conditions- Advanced in vivo, ex vivo, and computational methodologies for studying EGC function across aging- Translational and drug discovery approaches targeting glial and immune pathways within the gut-brain axisThis Research Topic will accept original research articles, reviews, mini-reviews, meta-analyses, and opinion pieces that deepen the field’s understanding of enteric glial physiology and pharmacological strategies to counter brain aging and neurodegeneration. This Research Topic is centered on enteric glial mechanisms in the context of aging and neurodegeneration; studies focused primarily on the gut microbiome or intestinal barrier without a direct enteric glial component may fall outside the intended scope. Submissions addressing acute gastrointestinal conditions, pediatric or developmental models, or neuropathies unrelated to aging are also likely to be a poor fit for this Topic.The Topic Editors declare no competing interests in relation to this Research Topic. Topic editors: Giuseppe Esposito, Irene Palenca, Vladimir Grubišić Source: https://www.frontiersin.org/research-topics/83196/enteric-glial-cells-in-brain-aging-and-neurodegeneration-from-historical-roots-to-neuroinflammatory-paradigms-in-the-gut-brain-axis