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Cells
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The Emerging Role of Astrocytes in Health and Neurological Diseases
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The Emerging Role of Astrocytes in Health and Neurological Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 12911

Special Issue Editor

Dr. Italia Di Liegro

E-Mail Website
Guest Editor
Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università degli Studi di Palermo, Via del Vespro 129, 90127 Palermo, Italy
Interests: post-transcriptional regulation of gene expression; RNA–protein interactions; role of extracellular vesicles in the nervous system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For a long time, astrocytes have mainly been considered for the metabolic support they provide to neurons and their ability to regulate the extracellular levels of many molecules, from ions to neurotransmitters, thus ensuring the maintenance of the best environment for neuronal functioning. More recently, however, it is becoming increasingly clear that astrocyte functions are more complex: they can respond to many neurotransmitters and release their own signaling molecules (gliotransmitters), thus regulating neuronal firing. Initially, the term “tripartite synapse” was proposed to describe the interaction between astrocytes and synapses; however, it has since been realized that astrocytes actually form a sort of network, kept together by gap junctions. Thanks to this organization, astrocytes can actually embrace many synapses at a time, and neurons can thus interact with each other even when they are not close together (“lateral regulation”). All these connections are fundamental for the basic function of the nervous system and also for the highest cognitive abilities. However, the same connections become a serious problem when the normal functioning of neurons and/or astrocytes is compromised. This Special Issue aims to discuss, in particular, the role of astrocytes in healthy and pathological conditions.

Dr. Italia Di Liegro
Guest Editor

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Keywords

  • astrocyte network
  • gliotransmitters
  • astrocytes in learning and memory
  • astrocytes and the blood–brain barrier
  • astrocyte pathologies

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Published Papers (6 papers)

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Research

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20 pages, 4892 KiB  
Article
Abnormal Morphology and Synaptogenic Signaling in Astrocytes Following Prenatal Opioid Exposure
by Ethan B. Niebergall, Daron Weekley, Anna Mazur, Nathan A. Olszewski, Kayla M. DeSchepper, N. Radant, Aishwarya S. Vijay and W. Christopher Risher
Cells 2024, 13(10), 837; https://doi.org/10.3390/cells13100837 - 14 May 2024
Viewed by 1421
Abstract
In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system [...] Read more.
In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and morphological development in cortical cell culture. Acute buprenorphine treatment had no effect on the excitatory synapse number in astrocyte-free neuron cultures. In conditions where neurons shared culture media with astrocytes, buprenorphine attenuated the synaptogenic capabilities of astrocyte-secreted factors. Neurons cultured from drug-naïve mice showed no change in synapses when treated with factors secreted by astrocytes from POE mice. However, this same treatment was synaptogenic when applied to neurons from POE mice, indicating a complex neuroadaptive response in the event of impaired astrocyte signaling. In addition to promoting morphological and connectivity changes in neurons, POE exerted a strong influence on astrocyte development, disrupting their structural maturation and promoting the accumulation of lipid droplets (LDs), suggestive of a maladaptive stress response in the developing CNS. Full article
(This article belongs to the Special Issue The Emerging Role of Astrocytes in Health and Neurological Diseases)
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Review

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24 pages, 964 KiB  
Review
Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes
by Polina Shichkova, Jay S. Coggan, Henry Markram and Daniel Keller
Cells 2024, 13(20), 1714; https://doi.org/10.3390/cells13201714 - 17 Oct 2024
Viewed by 1993
Abstract
The regulation of energy in the brain has garnered substantial attention in recent years due to its significant implications in various disorders and aging. The brain’s energy metabolism is a dynamic and tightly regulated network that balances energy demand and supply by engaging [...] Read more.
The regulation of energy in the brain has garnered substantial attention in recent years due to its significant implications in various disorders and aging. The brain’s energy metabolism is a dynamic and tightly regulated network that balances energy demand and supply by engaging complementary molecular pathways. The crosstalk among these pathways enables the system to switch its preferred fuel source based on substrate availability, activity levels, and cell state-related factors such as redox balance. Brain energy production relies on multi-cellular cooperation and is continuously supplied by fuel from the blood due to limited internal energy stores. Astrocytes, which interface with neurons and blood vessels, play a crucial role in coordinating the brain’s metabolic activity, and their dysfunction can have detrimental effects on brain health. This review characterizes the major energy substrates (glucose, lactate, glycogen, ketones and lipids) in astrocyte metabolism and their role in brain health, focusing on recent developments in the field. Full article
(This article belongs to the Special Issue The Emerging Role of Astrocytes in Health and Neurological Diseases)
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29 pages, 1639 KiB  
Review
Gut–Brain Interactions and Their Impact on Astrocytes in the Context of Multiple Sclerosis and Beyond
by Julia Zißler, Veit Rothhammer and Mathias Linnerbauer
Cells 2024, 13(6), 497; https://doi.org/10.3390/cells13060497 - 13 Mar 2024
Cited by 7 | Viewed by 2383
Abstract
Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) that leads to physical and cognitive impairment in young adults. The increasing prevalence of MS underscores the critical need for innovative therapeutic approaches. Recent advances in neuroimmunology have [...] Read more.
Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) that leads to physical and cognitive impairment in young adults. The increasing prevalence of MS underscores the critical need for innovative therapeutic approaches. Recent advances in neuroimmunology have highlighted the significant role of the gut microbiome in MS pathology, unveiling distinct alterations in patients’ gut microbiota. Dysbiosis not only impacts gut-intrinsic processes but also influences the production of bacterial metabolites and hormones, which can regulate processes in remote tissues, such as the CNS. Central to this paradigm is the gut–brain axis, a bidirectional communication network linking the gastrointestinal tract to the brain and spinal cord. Via specific routes, bacterial metabolites and hormones can influence CNS-resident cells and processes both directly and indirectly. Exploiting this axis, novel therapeutic interventions, including pro- and prebiotic treatments, have emerged as promising avenues with the aim of mitigating the severity of MS. This review delves into the complex interplay between the gut microbiome and the brain in the context of MS, summarizing current knowledge on the key signals of cross-organ crosstalk, routes of communication, and potential therapeutic relevance of the gut microbiome. Moreover, this review places particular emphasis on elucidating the influence of these interactions on astrocyte functions within the CNS, offering insights into their role in MS pathophysiology and potential therapeutic interventions. Full article
(This article belongs to the Special Issue The Emerging Role of Astrocytes in Health and Neurological Diseases)
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24 pages, 1812 KiB  
Review
Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood–Brain Barrier
by Gabriella Schiera, Carlo Maria Di Liegro, Giuseppe Schirò, Gabriele Sorbello and Italia Di Liegro
Cells 2024, 13(2), 150; https://doi.org/10.3390/cells13020150 - 12 Jan 2024
Cited by 13 | Viewed by 2966
Abstract
The blood–brain barrier (BBB) is a fundamental structure that protects the composition of the brain by determining which ions, metabolites, and nutrients are allowed to enter the brain from the blood or to leave it towards the circulation. The BBB is structurally composed [...] Read more.
The blood–brain barrier (BBB) is a fundamental structure that protects the composition of the brain by determining which ions, metabolites, and nutrients are allowed to enter the brain from the blood or to leave it towards the circulation. The BBB is structurally composed of a layer of brain capillary endothelial cells (BCECs) bound to each other through tight junctions (TJs). However, its development as well as maintenance and properties are controlled by the other brain cells that contact the BCECs: pericytes, glial cells, and even neurons themselves. Astrocytes seem, in particular, to have a very important role in determining and controlling most properties of the BBB. Here, we will focus on these latter cells, since the comprehension of their roles in brain physiology has been continuously expanding, even including the ability to participate in neurotransmission and in complex functions such as learning and memory. Accordingly, pathological conditions that alter astrocytic functions can alter the BBB’s integrity, thus compromising many brain activities. In this review, we will also refer to different kinds of in vitro BBB models used to study the BBB’s properties, evidencing its modifications under pathological conditions. Full article
(This article belongs to the Special Issue The Emerging Role of Astrocytes in Health and Neurological Diseases)
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21 pages, 6314 KiB  
Review
Mechanisms of Activation of Brain’s Drainage during Sleep: The Nightlife of Astrocytes
by Dmitry Postnov, Oxana Semyachkina-Glushkovskaya, Elena Litvinenko, Jürgen Kurths and Thomas Penzel
Cells 2023, 12(22), 2667; https://doi.org/10.3390/cells12222667 - 20 Nov 2023
Cited by 6 | Viewed by 2202
Abstract
The study of functions, mechanisms of generation, and pathways of movement of cerebral fluids has a long history, but the last decade has been especially productive. The proposed glymphatic hypothesis, which suggests a mechanism of the brain waste removal system (BWRS), caused an [...] Read more.
The study of functions, mechanisms of generation, and pathways of movement of cerebral fluids has a long history, but the last decade has been especially productive. The proposed glymphatic hypothesis, which suggests a mechanism of the brain waste removal system (BWRS), caused an active discussion on both the criticism of some of the perspectives and our intensive study of new experimental facts. It was especially found that the intensity of the metabolite clearance changes significantly during the transition between sleep and wakefulness. Interestingly, at the cellular level, a number of aspects of this problem have been focused on, such as astrocytes–glial cells, which, over the past two decades, have been recognized as equal partners of neurons and perform many important functions. In particular, an important role was assigned to astrocytes within the framework of the glymphatic hypothesis. In this review, we return to the “astrocytocentric” view of the BWRS function and the explanation of its activation during sleep from the viewpoint of new findings over the last decade. Our main conclusion is that the BWRS’s action may be analyzed both at the systemic (whole-brain) and at the local (cellular) level. The local level means here that the neuro-glial-vascular unit can also be regarded as the smallest functional unit of sleep, and therefore, the smallest functional unit of the BWRS. Full article
(This article belongs to the Special Issue The Emerging Role of Astrocytes in Health and Neurological Diseases)
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Other

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14 pages, 1167 KiB  
Systematic Review
A Systematic Review of Delta-9-Tetrahydrocannabinol (∆9-THC) in Astrocytic Markers
by Christian Ramos-Jiménez, Sarah Petkau and Romina Mizrahi
Cells 2024, 13(19), 1628; https://doi.org/10.3390/cells13191628 - 29 Sep 2024
Viewed by 1359
Abstract
Background: Astrocytic reactivity in substance use disorders (SUDs) has been extensively studied, yet the molecular effect of delta-9-tetrahydrocannabinol (∆9-THC, the main psychoactive compound in cannabis) on glial cells, especially astrocytes, remains poorly understood. Exploring ∆9-THC’s impact on astrocytic markers can provide insight into [...] Read more.
Background: Astrocytic reactivity in substance use disorders (SUDs) has been extensively studied, yet the molecular effect of delta-9-tetrahydrocannabinol (∆9-THC, the main psychoactive compound in cannabis) on glial cells, especially astrocytes, remains poorly understood. Exploring ∆9-THC’s impact on astrocytic markers can provide insight into its effects on brain functions such as homeostasis, synaptic transmission, and response to neuronal injury. This systematic review synthesizes findings from studies investigating ∆9-THC’s impact on astrocytic markers. Methods: A systematic review was conducted using EMBASE, Medline, and PsychoInfo via the OvidSP platform. Studies reporting astrocytic markers following ∆9-THC exposure in animals and humans were included. Data were extracted from twelve eligible full-text articles, and the risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation. Results: This research identified several astrocytic markers, including glial fibrillary acidic protein (GFAP), nestin, and glutamate–aspartate transporter (GLAST). Both GFAP and nestin expressions increased in adulthood following adolescence and adult ∆9-THC exposure. An increase in GLAST expression was also noted during early development after ∆9-THC exposure. Conclusions: This review indicates varying levels of astrocytic reactivity to ∆9-THC across different developmental stages, including adolescence and adulthood. ∆9-THC appears to impact maturation, particularly during early developmental stages, and exhibits sex-dependent effects. Full article
(This article belongs to the Special Issue The Emerging Role of Astrocytes in Health and Neurological Diseases)
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