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Role of Glia in Human Health and Disease—2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 1642

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Guest Editor
Department of Health Sciences, University of Florence, 50134 Florence, Italy
Interests: neuropharmacology; neurodegeneration; neuroinflammation; glia; microbiota; neurodegenerative diseases; hippocampus; behaviour
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Special Issue Information

Dear Colleagues,

The majority of brain cells are glia, and yet, over a century after their discovery, their real functions have still not been fully unraveled. Currently, our understanding of the role of glia in central nervous system (CNS) physiology and in neurodevelopmental, neurodegenerative, and demyelinating pathology is rapidly progressing. Glia, with their multiple functions, maintain the homeostasis of the CNS. Astrocytes are the most numerous and ubiquitous glial cells in the CNS and have many housekeeping functions; they bind the gray matter and enwrap synapses, maintain ion and neurotransmitter homeostasis, and regulate synaptogenesis. Microglia, the primary immune cells of the central nervous system, dynamically and continuously survey brain parenchyma to detect and eliminate debris from damaged neurons via phagocytosis and participate in shaping synaptic connectivity in the developing brain. Oligodendrocytes and Schwann cells myelinate axons, shaping the connectome.

Glia are vital, as their interactions with neurons determine the operation of the brain in health and disease states. These interactions form the basis of networks that show morphological and functional reciprocal reliance and dependency.

Alterations affecting one cell population reverberate and affect the others, favoring or dysregulating their activities. Glial cell phenomic dysfunction, whether in the form of atrophy with loss of function or reactivity, is associated with brain diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and glioblastoma, as well as autism and psychiatric disorders. Understanding the roles of glia will allow us to assess how their interactions can influence the state and progression of diseases and will be critical in identifying therapeutic strategies.

This Special Issue will comprise an in-depth analysis of how different types of glia participate in the physiological and pathological mechanisms behind CNS function and contribute to the onset or progression of brain diseases. In this regard, investigators are invited to contribute original research articles and reviews to improve our understanding of the role of glia in health and disease.

Dr. Daniele Lana
Guest Editor

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Keywords

  • astrocytes
  • microglia
  • oligodendrocytes
  • Schwann cells
  • neurodegeneration

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Published Papers (2 papers)

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18 pages, 13137 KB  
Article
Microglial Activation Is Associated with Hippocampal Synaptic Degeneration and Cognitive Deficits Following Repeated Propofol Exposure
by Liyun Deng, Mengchan Su, Ying Cui, Jiahui Wu, Guo Chen, Ruotian Jiang and Chan Chen
Int. J. Mol. Sci. 2026, 27(14), 6293; https://doi.org/10.3390/ijms27146293 - 15 Jul 2026
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Abstract
Propofol is a widely used intravenous anesthetic with recognized abuse potential; however, the effects of repeated propofol exposure on hippocampal function and cognition remain poorly understood. In the present study, we established a rat model of repeated subanesthetic intraperitoneal propofol administration and demonstrated [...] Read more.
Propofol is a widely used intravenous anesthetic with recognized abuse potential; however, the effects of repeated propofol exposure on hippocampal function and cognition remain poorly understood. In the present study, we established a rat model of repeated subanesthetic intraperitoneal propofol administration and demonstrated that propofol induced robust conditioned place preference, indicating rewarding properties. Propofol-exposed rats exhibited significant impairments in hippocampus-dependent cognitive tasks. Transcriptomic analysis revealed marked transcriptional alterations enriched in pathways related to synaptic organization and plasticity following repeated propofol exposure. Consistently, Western blotting, transmission electron microscopy, and Golgi staining demonstrated pronounced reductions in dendritic spine density and synaptic integrity within the hippocampus. Moreover, aberrant microglial activation was observed in the hippocampus and was closely associated with synaptic degeneration and cognitive deficits. Importantly, pharmacological inhibition of microglial activation with minocycline effectively ameliorated propofol-induced cognitive impairment and synaptic degeneration. Collectively, these findings suggest that microglial activation is associated with hippocampal synaptic degeneration and cognitive deficits following repeated propofol exposure and may contribute to these pathological changes. Full article
(This article belongs to the Special Issue Role of Glia in Human Health and Disease—2nd Edition)
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10 pages, 2529 KB  
Brief Report
SPARCL1 Enrichment at the Glioblastoma Invasive Front Is Consistent with Synaptogenic and Angiogenic Tumor Niches
by JuliAnne E. Allgood, Torrance Johnson and Jessica E. Pullan
Int. J. Mol. Sci. 2026, 27(9), 4017; https://doi.org/10.3390/ijms27094017 - 30 Apr 2026
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Abstract
Astrocytes regulate key aspects of the neural microenvironment that can be co-opted by cancer to support tumor growth and invasion. Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is a matricellular glycoprotein expressed by astrocytes and stromal cells, whose expression varies across [...] Read more.
Astrocytes regulate key aspects of the neural microenvironment that can be co-opted by cancer to support tumor growth and invasion. Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is a matricellular glycoprotein expressed by astrocytes and stromal cells, whose expression varies across cancer types. While SPARCL1 is downregulated in many peripheral cancers, reports of its expression in gliomas, specifically glioblastoma (GBM), are inconsistent. The biological context underlying these divergent findings, and the role of SPARCL1 in GBM malignancy, remains unclear. Publicly available transcriptomic datasets from the Ivy Glioblastoma Atlas Project (Ivy GAP), GlioVis, and TCGA were analyzed to evaluate SPARCL1 expression across GBM cohorts. Spatially resolved gene expression data from Ivy GAP were used to assess SPARCL1 expression from defined tumor regions. Microarray and RNA sequencing datasets from GlioVis and TCGA, respectively, were used to assess SPARCL1 expression across whole-tumor samples. Spatial transcriptomics from Ivy GAP show SPARCL1 expression was upregulated along the leading edge and in infiltrating tumor regions. Microarray datasets showed greater SPARCL1 expression in tumors of astrocyte lineage as opposed to oligodendrocyte lineage. Bulk RNA sequencing showed high SPARCL1 expression in low-grade gliomas, which is consistent with astrocytic lineage, IDH mutation, and spatial averaging effects that might obscure regional associations. These findings demonstrate that SPARCL1 expression in GBM is shaped by tumor architecture, molecular classification, and microenvironment interactions. Enrichment of SPARCl1 at invasive tumor margins is consistent with prior studies linking SPARCL1 to neuron–glioma synapse formation and angiogenesis. Full article
(This article belongs to the Special Issue Role of Glia in Human Health and Disease—2nd Edition)
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