Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Язык: Английский

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Astrocyte energy and neurotransmitter metabolism in Alzheimer’s disease: Integration of the glutamate/GABA-glutamine cycle

Progress in Neurobiology, Год журнала: 2022, Номер 217, С. 102331 - 102331

Опубликована: Июль 21, 2022

Язык: Английский

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Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Янв. 26, 2022

Mechanical damage is one of the predisposing factors inflammation, and it runs through entire inflammatory pathological process. Repeated or persistent damaging mechanical irritation leads to chronic diseases. The mechanism how forces induce inflammation not fully understood. Piezo1 a newly discovered mechanically sensitive ion channel. channel opens in response stimuli, transducing signals into an cascade cell leading tissue inflammation. A large amount evidence shows that plays vital role occurrence progression This mini-review briefly presents new responds different stresses trigger various tissues. discovery provides insights for treatment diseases related stress. Inhibiting transduction can inhibit improve outcome at early stage. pharmacology has shown bright prospects. development tissue-specific drugs clinical use may be target treating

Язык: Английский

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Ultrastructural view of astrocyte arborization, astrocyte-astrocyte and astrocyte-synapse contacts, intracellular vesicle-like structures, and mitochondrial network

Progress in Neurobiology, Год журнала: 2022, Номер 213, С. 102264 - 102264

Опубликована: Март 11, 2022

Язык: Английский

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Astrocyte regulation of neural circuit activity and network states

Glia, Год журнала: 2022, Номер 70(8), С. 1455 - 1466

Опубликована: Апрель 22, 2022

Abstract Astrocytes are known to influence neuronal activity through different mechanisms, including the homeostatic control of extracellular levels ions and neurotransmitters exchange signaling molecules that regulate synaptic formation, structure, function. While a great effort done in past has defined many molecular mechanisms cellular processes involved astrocyte‐neuron interactions at level, consequences these network level vivo have only relatively recently been identified. This review describes discusses recent findings on regulatory effects astrocytes networks vivo. Accumulating but still limited, evidence indicates rhythmic synchronization as well brain states. These studies demonstrate critical contribution paving way for more thorough understanding bases

Язык: Английский

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Calcium signaling in astrocytes and gliotransmitter release

Frontiers in Synaptic Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Март 2, 2023

Glia are as numerous in the brain neurons and widely known to serve supportive roles such structural scaffolding, extracellular ionic neurotransmitter homeostasis, metabolic support. However, over past two decades, several lines of evidence indicate that astrocytes, which a type glia, play active neural information processing. Astrocytes, although not electrically active, can exhibit form excitability by dynamic changes intracellular calcium levels. They sense synaptic activity release neuroactive substances, named gliotransmitters, modulate neuronal transmission areas, thus impacting animal behavior. This "dialogue" between astrocytes is embodied concept tripartite synapse includes integral elements function. Here, we review recent work discuss how via calcium-mediated processing at various spatial time scales.

Язык: Английский

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Milestone Review: Metabolic dynamics of glutamate and GABA mediated neurotransmission — The essential roles of astrocytes

Journal of Neurochemistry, Год журнала: 2023, Номер 166(2), С. 109 - 137

Опубликована: Март 15, 2023

Abstract Since it was first generally accepted that the two amino acids glutamate and GABA act as principal neurotransmitters, several landmark discoveries relating to this function have been uncovered. Synaptic homeostasis of these transmitters involves cell types working in close collaboration is facilitated by specialized cellular processes. Notably, are extensively recycled between neurons astrocytes a process known glutamate/GABA‐glutamine cycle, which essential maintain synaptic transmission. The cycle intimately coupled energy metabolism relies on metabolic both astrocytes. Importantly, display unique features allowing extensive metabolite release, hereby providing support for neurons. Furthermore, undergo complex adaptations response injury pathology, may greatly affect transmission during disease. In Milestone Review we outline major relation balancing signaling, including uptake, metabolism, recycling. We provide special focus how astrocyte contribute sustain neuronal through transfer. Recent advances reviewed context brain toxicity neurodegeneration. Finally, consider pathological serve potential target intervention. Integrating multitude fine‐tuned processes supporting neurotransmitter recycling, will aid next generation homeostasis. image

Язык: Английский

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Astrocyte morphology

Trends in Cell Biology, Год журнала: 2023, Номер 34(7), С. 547 - 565

Опубликована: Окт. 26, 2023

Astrocytes are predominant glial cells that tile the central nervous system (CNS). A cardinal feature of astrocytes is their complex and visually enchanting morphology, referred to as bushy, spongy, star-like. precept this review such morphological shapes evolved allow contact signal with diverse at a range distances in order sample, regulate, contribute extracellular milieu, thus participate widely cell–cell signaling during physiology disease. The recent use improved imaging methods cell-specific molecular evaluations has revealed new information on structural organization underpinnings astrocyte mechanisms morphogenesis, contributions disease states reduced morphology. These insights have reignited interest complexity cornerstone fundamental biology critical substrate for multicellular spatial physiological interactions CNS.

Язык: Английский

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Electroacupuncture prevents astrocyte atrophy to alleviate depression

Cell Death and Disease, Год журнала: 2023, Номер 14(5)

Опубликована: Май 29, 2023

Abstract Astrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and animal models depression. Here we show that electroacupuncture prevents astrocyte prefrontal cortex alleviates depressive-like behaviour mice subjected to chronic unpredictable mild stress (CUMS). Treatment with CUMS induced phenotypes as confirmed by sucrose preference test, tail suspension forced swimming test. These behavioural changes were paralleled morphological astrocytes cortex, revealed analysis 3D reconstructions confocal Z-stack images mCherry expressing astrocytes. This was accompanied a decrease expression cytoskeletal linker Ezrin, associated formation astrocytic leaflets, which form astroglial synaptic cradle. Electroacupuncture at acupoint ST36, well treatment anti-depressant fluoxetine, prevented behaviours, atrophy, down-regulation ezrin. In conclusion, our data further strengthen notion primary role depression reveal cellular target for disorders.

Язык: Английский

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Axonal energy metabolism, and the effects in aging and neurodegenerative diseases

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Июль 20, 2023

Abstract Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of (NDAs), such as Alzheimer’s disease, Parkinson’s Huntington’s Amyotrophic lateral sclerosis. Glucose is the major brain fuel glucose hypometabolism has been observed regions vulnerable to NDAs. Many susceptible are topological central hub connectome, linked by densely interconnected long-range axons. Axons, key components have high metabolic needs support neurotransmission other essential activities. Long-range axons particularly injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy often an early sign neurodegeneration. Recent ascribe axonal maintenance failures local dysregulation. With this review, we aim stimulate research exploring metabolically oriented neuroprotection strategies enhance or normalize bioenergetics NDA models. Here start summarizing evidence from human patients animal models reveal correlation between connectomic disintegration aging/NDAs. To encourage mechanistic investigations on how dysregulation occurs during aging/NDAs, first review current literature distinct subdomains: axon initial segments, myelinated arbors harboring pre-synaptic boutons. In each subdomain, focus organization, activity-dependent regulation system, external glial support. Second, mechanisms regulating nicotinamide adenine dinucleotide (NAD + ) homeostasis, molecule for energy metabolism processes, including NAD biosynthetic, recycling, consuming pathways. Third, highlight innate vulnerability connectome discuss its perturbation As deficits developing into NDAs, especially asymptomatic phase, they likely exaggerated further impaired energetic cost neural network hyperactivity, pathology. Future interrogating causal relationship vulnerability, axonopathy, amyloid/tau pathology, cognitive decline will provide fundamental knowledge therapeutic interventions.

Язык: Английский

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