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Immune Functions of Astrocytes
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Immune Functions of Astrocytes

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 16241

Special Issue Editors

Dr. Hiroko Ikeshima-Kataoka

E-Mail Website
Guest Editor
Department of Biology, Keio University, 4-1-1, Hiyoshi, Kohoku-ku, Yokohama 223-8521, Japan
Interests: activated atrocytes; blood–brain barrier integrity; blood stream; blood vessel; endothelial cell; neuroinflammation; microglia; pericyte; traumatic brain injury
Dr. Maja Potokar

E-Mail Website
Guest Editor
Laboratory of Neuroendocrinology–Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia
Interests: astroglia; neurons; cytoskeleton; vesicle trafficking; neuroinfections; autophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Astrocytes, specialized glial cells in the central nervous system (CNS), have a plethora of functions in the brain and the spinal cord. Among others, astrocytes maintain the integrity of the blood–brain barrier and control blood flow; constitute a tripartite synapse and thus affect learning and memory consolidation by gliotransmission and signal integration; and provide neuronal support and control water homeostasis and glucose metabolism. In recent decades, a growing body of evidence has amassed, suggesting that astrocytes are critically involved not only in many physiological processes but also in different pathological conditions, where they contribute importantly to the development and modulation of neuropathologies. Namely, following CNS injury or infection, astrocytes change their morphological, molecular, and functional features; they become reactive and participate in the formation of glial scars together with microglial cells, pericytes, ependymal cells, and the extra-cellular matrix. Moreover, in an injured CNS, astrocytes critically affect innate and adaptive immune responses by releasing several cytokines and chemokines, thereby either exacerbating inflammatory processes and increasing tissue damage, or promoting immunosuppression and tissue repair. This Special Issue of the International Journal of Molecular Sciences will focus on the immune functions of astrocytes in connection to the CNS trauma and regeneration.

Dr. Hiroko Ikeshima-Kataoka
Dr. Maja Potokar
Guest Editors

Manuscript Submission Information

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Keywords

  • reactive astrocytes
  • blood–brain barrier integrity
  • blood stream
  • blood vessel
  • endothelial cell
  • neuroinflammation
  • neuroinfection
  • microglia
  • pericyte
  • ependyma
  • traumatic brain injury

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Published Papers (5 papers)

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Research

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10 pages, 1085 KiB  
Article
Age-Related Changes in Neurons and Satellite Glial Cells in Mouse Dorsal Root Ganglia
by Menachem Hanani, David C. Spray and Tian-Ying Huang
Int. J. Mol. Sci. 2023, 24(3), 2677; https://doi.org/10.3390/ijms24032677 - 31 Jan 2023
Cited by 3 | Viewed by 2182
Abstract
The effects of aging on the nervous system are well documented. However, most previous studies on this topic were performed on the central nervous system. The present study was carried out on the dorsal root ganglia (DRGs) of mice, and focused on age-related [...] Read more.
The effects of aging on the nervous system are well documented. However, most previous studies on this topic were performed on the central nervous system. The present study was carried out on the dorsal root ganglia (DRGs) of mice, and focused on age-related changes in DRG neurons and satellite glial cells (SGCs). Intracellular electrodes were used for dye injection to examine the gap junction-mediated coupling between neurons and SGCs, and for intracellular electrical recordings from the neurons. Tactile sensitivity was assessed with von Frey hairs. We found that 3-23% of DRG neurons were dye-coupled to SGCs surrounding neighboring neurons in 8–24-month (Mo)-old mice, whereas in young adult (3 Mo) mice, the figure was 0%. The threshold current for firing an action potential in sensory neurons was significantly lower in DRGs from 12 Mo mice compared with those from 3 Mo mice. The percentage of neurons with spontaneous subthreshold membrane potential oscillation was greater by two-fold in 12 Mo mice. The withdrawal threshold was lower by 22% in 12 Mo mice compared with 3 Mo ones. These results show that in the aged mice, a proportion of DRG neurons is coupled to SGCs, and that the membrane excitability of the DRG neurons increases with age. We propose that augmented neuron–SGC communications via gap junctions are caused by low-grade inflammation associated with aging, and this may contribute to pain behavior. Full article
(This article belongs to the Special Issue Immune Functions of Astrocytes)
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Review

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14 pages, 3010 KiB  
Review
Modern Microscopic Approaches to Astrocytes
by Mitsuhiro Morita
Int. J. Mol. Sci. 2023, 24(6), 5883; https://doi.org/10.3390/ijms24065883 - 20 Mar 2023
Cited by 4 | Viewed by 3291
Abstract
Microscopy started as the histological analysis based on intrinsic optical properties of tissues such as the refractive index and light absorption, and is expanding to include the visualization of organelles by chemical staining, localization of molecules by immunostaining, physiological measurements such as Ca [...] Read more.
Microscopy started as the histological analysis based on intrinsic optical properties of tissues such as the refractive index and light absorption, and is expanding to include the visualization of organelles by chemical staining, localization of molecules by immunostaining, physiological measurements such as Ca2+ imaging, functional manipulation by optogenetics, and comprehensive analysis of chemical composition by Raman spectra. The microscope is one of the most important tools in neuroscience, which aims to reveal the complex intercellular communications underlying brain function and pathology. Many aspects of astrocytes, including the structures of their fine processes and physiological activities in concert with neurons and blood vessels, were revealed in the course of innovations in modern microscopy. The evolution of modern microscopy is a consequence of breakthroughs in spatiotemporal resolutions and expansions in molecular and physiological targets due to the progress in optics and information technology, as well as the inventions of probes using organic chemistry and molecular biology. This review overviews the modern microscopic approach to astrocytes. Full article
(This article belongs to the Special Issue Immune Functions of Astrocytes)
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20 pages, 2960 KiB  
Review
Immune Functions of Astrocytes in Viral Neuroinfections
by Jernej Jorgačevski and Maja Potokar
Int. J. Mol. Sci. 2023, 24(4), 3514; https://doi.org/10.3390/ijms24043514 - 9 Feb 2023
Cited by 17 | Viewed by 2679
Abstract
Neuroinfections of the central nervous system (CNS) can be triggered by various pathogens. Viruses are the most widespread and have the potential to induce long-term neurologic symptoms with potentially lethal outcomes. In addition to directly affecting their host cells and inducing immediate changes [...] Read more.
Neuroinfections of the central nervous system (CNS) can be triggered by various pathogens. Viruses are the most widespread and have the potential to induce long-term neurologic symptoms with potentially lethal outcomes. In addition to directly affecting their host cells and inducing immediate changes in a plethora of cellular processes, viral infections of the CNS also trigger an intense immune response. Regulation of the innate immune response in the CNS depends not only on microglia, which are fundamental immune cells of the CNS, but also on astrocytes. These cells align blood vessels and ventricle cavities, and consequently, they are one of the first cell types to become infected after the virus breaches the CNS. Moreover, astrocytes are increasingly recognized as a potential viral reservoir in the CNS; therefore, the immune response initiated by the presence of intracellular virus particles may have a profound effect on cellular and tissue physiology and morphology. These changes should be addressed in terms of persisting infections because they may contribute to recurring neurologic sequelae. To date, infections of astrocytes with different viruses originating from genetically distinct families, including Flaviviridae, Coronaviridae, Retroviridae, Togaviridae, Paramyxoviridae, Picomaviridae, Rhabdoviridae, and Herpesviridae, have been confirmed. Astrocytes express a plethora of receptors that detect viral particles and trigger signaling cascades, leading to an innate immune response. In this review, we summarize the current knowledge on virus receptors that initiate the release of inflammatory cytokines from astrocytes and depict the involvement of astrocytes in immune functions of the CNS. Full article
(This article belongs to the Special Issue Immune Functions of Astrocytes)
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17 pages, 2435 KiB  
Review
Astrocyte Immune Functions and Glaucoma
by Youichi Shinozaki, Kenji Kashiwagi and Schuichi Koizumi
Int. J. Mol. Sci. 2023, 24(3), 2747; https://doi.org/10.3390/ijms24032747 - 1 Feb 2023
Cited by 3 | Viewed by 3464
Abstract
Astrocytes, a non-neuronal glial cell type in the nervous system, are essential for regulating physiological functions of the central nervous system. In various injuries and diseases of the central nervous system, astrocytes often change their phenotypes into neurotoxic ones that participate in pro-inflammatory [...] Read more.
Astrocytes, a non-neuronal glial cell type in the nervous system, are essential for regulating physiological functions of the central nervous system. In various injuries and diseases of the central nervous system, astrocytes often change their phenotypes into neurotoxic ones that participate in pro-inflammatory responses (hereafter referred to as “immune functions”). Such astrocytic immune functions are not only limited to brain diseases but are also found in ocular neurodegenerative diseases such as glaucoma, a retinal neurodegenerative disease that is the leading cause of blindness worldwide. The eye has two astrocyte-lineage cells: astrocytes and Müller cells. They maintain the physiological environment of the retina and optic nerve, thereby controlling visual function. Dysfunction of astrocyte-lineage cells may be involved in the onset and progression of glaucoma. These cells become reactive in glaucoma patients, and animal studies have suggested that their immune responses may be linked to glaucoma-related events: tissue remodeling, neuronal death, and infiltration of peripheral immune cells. In this review, we discuss the role of the immune functions of astrocyte-lineage cells in the pathogenesis of glaucoma. Full article
(This article belongs to the Special Issue Immune Functions of Astrocytes)
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17 pages, 743 KiB  
Review
Astrocytic Neuroimmunological Roles Interacting with Microglial Cells in Neurodegenerative Diseases
by Mari Gotoh, Yasunori Miyamoto and Hiroko Ikeshima-Kataoka
Int. J. Mol. Sci. 2023, 24(2), 1599; https://doi.org/10.3390/ijms24021599 - 13 Jan 2023
Cited by 17 | Viewed by 3629
Abstract
Both astrocytic and microglial functions have been extensively investigated in healthy subjects and neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently and is making dramatic progress. In this review paper, we mostly focus on [...] Read more.
Both astrocytic and microglial functions have been extensively investigated in healthy subjects and neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently and is making dramatic progress. In this review paper, we mostly focus on the functional role of astrocytes in the extracellular matrix and on interactions between reactive astrocytes and reactive microglia in normal states and in neurodegenerative diseases, because the authors feel it is necessary to elucidate the mechanisms among activated glial cells in the pathology of neurological diseases in order to pave the way for drug discovery. Finally, we will review cyclic phosphatidic acid (cPA), a naturally occurring phospholipid mediator that induces a variety of biological activities in the brain both in vivo and in vitro. We propose that cPA may serve as a novel therapeutic molecule for the treatment of brain injury and neuroinflammation. Full article
(This article belongs to the Special Issue Immune Functions of Astrocytes)
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