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The Multifaceted Roles of Glia: From Cellular Functions to Neurological...
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The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications

A special issue of Neuroglia (ISSN 2571-6980).

Deadline for manuscript submissions: closed (31 July 2025) | Viewed by 10005

Special Issue Editor

Dr. Penha Barradas

E-Mail Website
Guest Editor
Departament of Pharmacology and Psychobiology, Roberto Alcantara Gomes Biology Institute (IBRAG), Rio de Janeiro State University (UERJ), Rio de Janeiro 20551-030, Brazil
Interests: developmental neurobiology; glial cell differentiation; hypoxia–ischemia in neurodevelopment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are excited to announce a Special Issue titled "The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications". This Special Issue aims to explore the diverse and critical functions of glial cells in the central nervous system, highlighting their roles not only in supporting neuronal health but also in modulating synaptic activity, neuroinflammation, and neurodegeneration. As researchers in the field, we invite you to contribute your findings that delve into the complex interactions between glia and neurons, the implications of glial dysfunction in various neurological disorders, and innovative therapeutic approaches targeting glial cells. Your work can help illuminate the intricate network of cellular communications that underpin brain function and disease. Join us in advancing our understanding of glial biology and its significance in neuroscience. We look forward to your submissions that will enrich this essential dialogue in our field.

Dr. Penha Barradas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Neuroglia is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microglia
  • astroglia
  • oligodendroglia
  • neuroinflammation
  • glial roles in neurodevelopment
  • glial dysfunction

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Related Special Issue

Published Papers (6 papers)

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Research

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21 pages, 5560 KB  
Article
Astrocyte FABP7 Modulates Seizure Activity-Dependent Protein Expression in Mouse Brain
by Adam P. Berg, Shahroz H. Tariq, Carlos C. Flores, Micah Lefton, Yuji Owada, Christopher J. Davis, Thomas N. Ferraro, Jon M. Jacobs, Marina A. Gritsenko, Yool Lee, Wheaton L. Schroeder and Jason R. Gerstner
Neuroglia 2025, 6(3), 33; https://doi.org/10.3390/neuroglia6030033 - 3 Sep 2025
Viewed by 501
Abstract
Background/Objectives: Patients with epilepsy commonly experience patterns of seizures that change with sleep/wake behavior or diurnal rhythms. The cellular and molecular mechanisms that underlie these patterns in seizure activity are not well understood but may involve non-neuronal cells, such as astrocytes. Our previous [...] Read more.
Background/Objectives: Patients with epilepsy commonly experience patterns of seizures that change with sleep/wake behavior or diurnal rhythms. The cellular and molecular mechanisms that underlie these patterns in seizure activity are not well understood but may involve non-neuronal cells, such as astrocytes. Our previous studies show the critical importance of one specific astrocyte factor, the brain-type fatty acid binding protein Fabp7, in the regulation of time-of-day-dependent electroshock seizure threshold and neural activity-dependent gene expression in mice. Here, we examined whether Fabp7 influences differential seizure activity-dependent protein expression, by comparing Fabp7 knockout (KO) to wild-type (WT) mice under control conditions and after reaching the maximal electroshock seizure threshold (MEST). Methods: We analyzed the proteome in cortical–hippocampal extracts from MEST and SHAM groups of WT and KO mice using mass spectrometry (MS), followed by Gene Ontology (GO) and pathway analyses. GO and pathway analyses of all groups revealed a diverse set of up- and downregulated differentially expressed proteins (DEPs). Results: We identified 65 significant DEPs in the comparison of KO SHAM versus WT SHAM; 33 proteins were upregulated and 32 were downregulated. We found downregulation in mitochondrial-associated proteins in WT MEST compared to WT SHAM controls, including Slc1a4, Slc25a27, Cox7a2, Cox8a, Micos10, and Atp5mk. Several upregulated DEPs in the KO SHAM versus WT SHAM comparison were associated with the 20S proteasomal subunit, suggesting proteasomal activity is elevated in the absence of Fabp7 expression. We also observed 92 DEPs significantly altered in the KO MEST versus WT MEST, with 49 proteins upregulated and 43 downregulated. Conclusions: Together, these data suggest that the astrocyte Fabp7 regulation of time-of-day-mediated neural excitability is modulated by multiple cellular mechanisms, which include proteasomal pathways, independent of its role in activity-dependent gene expression. Full article
(This article belongs to the Special Issue The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications)
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Review

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550 KB  
Review
Current Knowledge in Planarian Glia and Its Future Implications in Modeling Neurodegenerative Diseases
by David Gonzalez, Víctor Alarcón and Constanza Vásquez-Doorman
Neuroglia 2025, 6(4), 37; https://doi.org/10.3390/neuroglia6040037 - 24 Sep 2025
Abstract
Neurodegenerative diseases are characterized by progressive loss of neurons and remain largely incurable. Numerous mammalian models have been developed to study the mechanisms underlying their physiopathology; however, their high cost, complexity and time requirements highlight the need for alternative systems. Glial cells are [...] Read more.
Neurodegenerative diseases are characterized by progressive loss of neurons and remain largely incurable. Numerous mammalian models have been developed to study the mechanisms underlying their physiopathology; however, their high cost, complexity and time requirements highlight the need for alternative systems. Glial cells are increasingly recognized as key contributors to neurodegenerative disease progression through non-cell autonomous mechanisms. Planarians possess a nervous system with diverse neuronal subtypes and glial cells, offering an attractive combination of evolutionary conservation and remarkable regenerative capacity. Unlike mammalian glia, planarian glia originate from phagocytic progenitors and exhibit distinctive molecular markers, including if-1, cali and cathepsin. Emerging evidence suggests that planarian glia may contribute to neurotransmitter homeostasis, neuron–glia interactions and phagocytic activity. Additionally, planarians display robust and quantifiable behavioral responses, making them well suited for modeling neurodegenerative disease. In this review, we summarize the current findings regarding neuronal subtypes and glial cells in planaria, emphasizing their relevance as a model system. Further research into planarian glia will be crucial for understanding their roles in pathological contexts and for exploring their potential applications in neurodegenerative diseases research. Planarian simplicity, regenerative capacity, and compatibility with high-throughput approaches position planarians as a powerful model for investigating the cellular and molecular mechanisms underlying neurodegenerative diseases and for identifying potential therapeutic targets. Full article
(This article belongs to the Special Issue The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications)
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27 pages, 708 KB  
Review
Environmental Enrichment as a Possible Adjunct Therapy in Autism Spectrum Disorder: Insights from Animal and Human Studies on the Implications of Glial Cells
by Enrique Hernández-Arteaga, Josué Antonio Camacho-Candia, Roxana Pluma-Romo, María Isabel Solís-Meza, Myriam Nayeli Villafuerte-Vega and Francisco Aguilar-Guevara
Neuroglia 2025, 6(2), 18; https://doi.org/10.3390/neuroglia6020018 - 25 Apr 2025
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Abstract
Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition influenced by genetic, environmental, and epigenetic factors, leading to cognitive, emotional, and social impairments. Due to the heterogeneity of ASD, conventional therapies often have limited effectiveness, highlighting the need for complementary interventions. Enriched [...] Read more.
Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition influenced by genetic, environmental, and epigenetic factors, leading to cognitive, emotional, and social impairments. Due to the heterogeneity of ASD, conventional therapies often have limited effectiveness, highlighting the need for complementary interventions. Enriched environments (EEs), characterized by enhanced sensory, cognitive, and motor stimulation, have shown promise in alleviating ASD symptoms. This review examines the role of glial cells in mediating the effects of EE. Methods: A literature review was conducted, analyzing studies on EE interventions in animal models and humans, with a focus on glial involvement in neuroplasticity and synaptic remodeling. Results: Evidence from animal models suggests that EE induces significant glial modifications, including increased synaptogenesis and enhanced neuronal connectivity. Studies in rodent models of ASD have demonstrated that EE reduces stereotypical behaviors, improves social interactions, and enhances cognitive function, effects that are closely associated with astrocyte and microglia activity. Similarly, human studies indicate that EE interventions lead to reduced autism symptom severity and improved cognitive outcomes, further supporting the hypothesis that glial cells play a central role in mediating the beneficial effects of EE. Conclusions: This review highlights the potential of EE as a modulator of the brain’s microenvironment, emphasizing the critical role of glial processes in ASD intervention. These findings suggest that future therapeutic strategies for ASD should integrate approaches that specifically target a glial function to optimize intervention outcomes. However, further research is needed to optimize EE protocols and address ASD heterogeneity. Full article
(This article belongs to the Special Issue The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications)
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16 pages, 2325 KB  
Review
Central and Peripheral Immunity Responses in Parkinson’s Disease: An Overview and Update
by Ghaidaa Ebrahim, Hunter Hutchinson, Melanie Gonzalez and Abeer Dagra
Neuroglia 2025, 6(2), 17; https://doi.org/10.3390/neuroglia6020017 - 4 Apr 2025
Cited by 1 | Viewed by 1927
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, with increasing evidence supporting the role of immune dysregulation in its pathophysiology. Neuroinflammation, mediated by microglial activation, pro-inflammatory cytokine production, and blood–brain barrier dysfunction, plays a crucial role in [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, with increasing evidence supporting the role of immune dysregulation in its pathophysiology. Neuroinflammation, mediated by microglial activation, pro-inflammatory cytokine production, and blood–brain barrier dysfunction, plays a crucial role in dopaminergic neuronal degeneration. Furthermore, peripheral immune changes, including T cell infiltration, gut microbiota dysbiosis, and systemic inflammation, contribute to disease progression. The bidirectional interaction between the central and peripheral immune systems suggests that immune-based interventions may hold therapeutic potential. While dopaminergic treatments remain the standard of care, immunomodulatory therapies, monoclonal antibodies targeting α-synuclein, and deep brain stimulation (DBS) have demonstrated immunological effects, though clinical efficacy remains uncertain. Advances in immune phenotyping offer new avenues for personalized treatment approaches, optimizing therapeutic responses by stratifying patients based on inflammatory biomarkers. This review highlights the complexities of immune involvement in PD and discusses emerging strategies targeting immune pathways to develop disease-modifying treatments. Full article
(This article belongs to the Special Issue The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications)
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14 pages, 24413 KB  
Review
Rosenfeld’s Staining: A Valuable Tool for In Vitro Assessment of Astrocyte and Microglia Morphology
by Alana Alves Farias, Ana Carla dos Santos Costa, Jéssica Teles Souza, Érica Novaes Soares, Cinthia Cristina de Oliveira Santos Costa, Ravena Pereira do Nascimento, Silvia Lima Costa, Victor Diogenes Amaral da Silva and Maria de Fátima Dias Costa
Neuroglia 2025, 6(2), 16; https://doi.org/10.3390/neuroglia6020016 - 3 Apr 2025
Viewed by 1823
Abstract
In homeostasis, the glial cells support pivotal functions, such as neuronal differentiation, neuroprotection, nutrition, drug metabolism, and immune response in the central nervous system (CNS). Among these cells, astrocytes and microglia have been highlighted due to their role in the pathogenesis of several [...] Read more.
In homeostasis, the glial cells support pivotal functions, such as neuronal differentiation, neuroprotection, nutrition, drug metabolism, and immune response in the central nervous system (CNS). Among these cells, astrocytes and microglia have been highlighted due to their role in the pathogenesis of several diseases or due to their role in the defense against several insults (ex., chemicals, and pathogens). In Vitro cytological analysis of astrocytes and microglia has contributed to the understanding of the role of morphological changes in glial cells associated with a neuroprotective or neurotoxic phenotype. Currently, the main tools used for the investigation of glial cell morphology in culture are phase contrast microscopy or immunolabeling/fluorescence microscopy. However, generally, phase contrast microscopy does not generate images with high resolution and therefore does not contribute to visualizing a single cell morphology in confluent cell cultures. On the other hand, immunolabeling requires high-cost consumable antibodies, epifluorescence microscope or confocal microscope, and presents critical steps during the procedure. Therefore, identifying a fast, reproducible, low-cost alternative method that allows the evaluation of glial morphology is essential, especially for neuroscientists from low-income countries. This article aims to revise the use of Rosenfeld’s staining, as an alternative low-cost and easy-to-reproduce method to analyze astrocytic and microglial morphology in culture. Additionally, it shows Rosenfeld’s staining as a valuable tool to analyze changes in neural cell morphology in toxicological studies. Full article
(This article belongs to the Special Issue The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications)
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18 pages, 689 KB  
Review
Beyond the Neuron: The Integrated Role of Glia in Psychiatric Disorders
by André Demambre Bacchi
Neuroglia 2025, 6(2), 15; https://doi.org/10.3390/neuroglia6020015 - 25 Mar 2025
Cited by 1 | Viewed by 2472
Abstract
In recent decades, substantial evidence has highlighted the integral roles of neuroglia, particularly astrocytes, microglia, oligodendrocytes, and ependymal cells, in the regulation of synaptic transmission, metabolic support, and immune mechanisms within the central nervous system. In addition to their structural role, these cells [...] Read more.
In recent decades, substantial evidence has highlighted the integral roles of neuroglia, particularly astrocytes, microglia, oligodendrocytes, and ependymal cells, in the regulation of synaptic transmission, metabolic support, and immune mechanisms within the central nervous system. In addition to their structural role, these cells actively modulate neurotransmitter homeostasis and influence neuronal plasticity, thereby affecting cognition, mood, and behavior. This review discusses how neuroglial alterations contribute to the pathophysiology of five common psychiatric disorders: major depression, bipolar disorder, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. We synthesized preclinical and clinical findings illustrating that glial dysfunction, including impaired myelination and aberrant neuroinflammatory responses, often parallels disease onset and severity. Moreover, we outline how disruptions in astrocytic glutamate uptake, microglia-mediated synaptic pruning, and blood–brain barrier integrity may underlie the neurobiological heterogeneity observed in these disorders. The therapeutic implications range from anti-inflammatory agents to investigational compounds that aim to stabilize glial function or promote remyelination. However, challenges due to interindividual variability, insufficient biomarkers, and the multifactorial nature of psychiatric illnesses remain. Advances in neuroimaging, liquid biopsy, and more precise molecular techniques may facilitate targeted interventions by stratifying patient subgroups with distinct glial phenotypes. Continued research is essential to translate these insights into clinically efficacious and safe treatments. Full article
(This article belongs to the Special Issue The Multifaceted Roles of Glia: From Cellular Functions to Neurological Implications)
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