Astrocytes Are a Key Target for Neurotropic Viral Infection.

Astrocytes are increasingly recognized as important viral host cells in the central nervous system. These cells can produce relatively high quantities of new virions. In part, this can be attributed to the characteristics of astrocyte metabolism and its abundant and dynamic cytoskeleton network.

Ketamine Reduces the Surface Density of the Astroglial Kir4.1 Channel and Inhibits Voltage-Activated Currents in a Manner Similar to the Action of Ba on K Currents.

A single sub-anesthetic dose of ketamine evokes rapid and long-lasting beneficial effects in patients with a major depressive disorder. However, the mechanisms underlying this effect are unknown. It has been proposed that astrocyte dysregulation of extracellular K concentration ([K]) alters neuronal excitability, thus contributing to depression.

Immune Functions of Astrocytes in Viral Neuroinfections.

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.

In human astrocytes neurotropic flaviviruses increase autophagy, yet their replication is autophagy-independent.

Astrocytes, an abundant type of glial cells, are the key cells providing homeostasis in the central nervous system. Due to their susceptibility to infection, combined with high resilience to virus-induced cell death, astrocytes are now considered one of the principal types of cells, responsible for virus retention and dissemination within the brain. Autophagy plays an important role in elimination of intracellular components and in maintaining cellular homeostasis and is also intertwined with the life cycle of viruses.

Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes.

Plectin, a high-molecular-mass cytolinker, is abundantly expressed in the central nervous system (CNS). Currently, a limited amount of data about plectin in the CNS prevents us from seeing the complete picture of how plectin affects the functioning of the CNS as a whole. Yet, by analogy to its role in other tissues, it is anticipated that, in the CNS, plectin also functions as the key cytoskeleton interlinking molecule.

Neurotropic Viruses, Astrocytes, and COVID-19.

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered in China, causing a new coronavirus disease, termed COVID-19 by the WHO on February 11, 2020. At the time of this paper (January 31, 2021), more than 100 million cases have been recorded, which have claimed over 2 million lives worldwide. The most important clinical presentation of COVID-19 is severe pneumonia; however, many patients present various neurological symptoms, ranging from loss of olfaction, nausea, dizziness, and headache to encephalopathy and stroke, with a high prevalence of inflammatory central nervous system (CNS) syndromes.

Inhibiting glycolysis rescues memory impairment in an intellectual disability Gdi1-null mouse.

Objectives: GDI1 gene encodes for αGDI, a protein controlling the cycling of small GTPases, reputed to orchestrate vesicle trafficking. Mutations in human GDI1 are responsible for intellectual disability (ID). In mice with ablated Gdi1, a model of ID, impaired working and associative short-term memory was recorded.

Insights into Cell Surface Expression, Supramolecular Organization, and Functions of Aquaporin 4 Isoforms in Astrocytes.

Aquaporin 4 (AQP4) is the most abundant water channel in the central nervous system (CNS). Its expression is confined to non-neuronal glial cells, predominantly to astrocytes that represent a heterogeneous glial cell type in the CNS. The membrane of astrocyte processes, which align brain capillaries and pia, is particularly rich in AQP4.

Methods for Monitoring Endocytosis in Astrocytes.

Endocytosis is a vesicle-based mechanism by which eukaryotic cells internalize extracellular material. There are several types of this universal mechanism linked to different types of endocytosed cargo, including pathogens; therefore, several approaches can be applied. Here, we describe techniques that are applicable to study the internalization of flaviviruses; dextrans; transporters, such as, glutamate transporter vGlut1; and peptidergic signaling molecules, including atrial natriuretic peptide into astrocytes, the most heterogeneous neuroglial cells, which play a key homeostatic role in the central nervous system.

The Diversity of Intermediate Filaments in Astrocytes.

Despite the remarkable complexity of the individual neuron and of neuronal circuits, it has been clear for quite a while that, in order to understand the functioning of the brain, the contribution of other cell types in the brain have to be accounted for. Among glial cells, astrocytes have multiple roles in orchestrating neuronal functions. Their communication with neurons by exchanging signaling molecules and removing molecules from extracellular space takes place at several levels and is governed by different cellular processes, supported by multiple cellular structures, including the cytoskeleton.

Indirect Role of AQP4b and AQP4d Isoforms in Dynamics of Astrocyte Volume and Orthogonal Arrays of Particles.

Water channel aquaporin 4 (AQP4) plays a key role in the regulation of water homeostasis in the central nervous system (CNS). It is predominantly expressed in astrocytes lining blood-brain and blood-liquor boundaries. AQP4a (M1), AQP4c (M23), and AQP4e, present in the plasma membrane, participate in the cell volume regulation of astrocytes.

ZIKV Strains Differentially Affect Survival of Human Fetal Astrocytes versus Neurons and Traffic of ZIKV-Laden Endocytotic Compartments.

Malformations of the fetal CNS, known as microcephaly, have been linked to Zika virus (ZIKV) infection. Here, the responses of mammalian and mosquito cell lines, in addition to primary human fetal astrocytes and neurons were studied following infection by ZIKV strains Brazil 2016 (ZIKV-BR), French Polynesia 2013 (ZIKV-FP), and Uganda #976 1947 (ZIKV-UG). Viral production, cell viability, infectivity rate, and mobility of endocytotic ZIKV-laden vesicles were compared.

Astrocytes in Flavivirus Infections.

Virus infections of the central nervous system (CNS) can manifest in various forms of inflammation, including that of the brain (encephalitis) and spinal cord (myelitis), all of which may have long-lasting deleterious consequences. Although the knowledge of how different viruses affect neural cells is increasing, understanding of the mechanisms by which cells respond to neurotropic viruses remains fragmented. Several virus types have the ability to infect neural tissue, and astrocytes, an abundant and heterogeneous neuroglial cell type and a key element providing CNS homeostasis, are one of the first CNS cell types to get infected.

AQP4e-Based Orthogonal Arrays Regulate Rapid Cell Volume Changes in Astrocytes.

Water channel aquaporin 4 (AQP4) plays a key role in the regulation of water homeostasis in the brain. It is predominantly expressed in astrocytes at the blood-brain and blood-liquor interfaces. Although several AQP4 isoforms have been identified in the mammalian brain, two, AQP4a (M1) and AQP4c (M23), have been confirmed to cluster into plasma membrane supramolecular structures, termed orthogonal arrays of particles (OAPs) and to enhance water transport through the plasma membrane.

Astrocytic Vesicle-based Exocytosis in Cultures and Acutely Isolated Hippocampal Rodent Slices.

Astrocytes are excitable neural cells that contribute to brain information processing via bidirectional communication with neurons. This involves the release of gliosignaling molecules that affect synapses patterning and activity. Mechanisms mediating the release of these molecules likely consist of non-vesicular and vesicular-based mechanisms.

Astrocyte Aquaporin Dynamics in Health and Disease.

The family of aquaporins (AQPs), membrane water channels, consists of diverse types of proteins that are mainly permeable to water; some are also permeable to small solutes, such as glycerol and urea. They have been identified in a wide range of organisms, from microbes to vertebrates and plants, and are expressed in various tissues. Here, we focus on AQP types and their isoforms in astrocytes, a major glial cell type in the central nervous system (CNS).

Impaired αGDI Function in the X-Linked Intellectual Disability: The Impact on Astroglia Vesicle Dynamics.

X-linked non-syndromic intellectual disability (XLID) is a common mental disorder recognized by cognitive and behavioral deficits. Mutations in the brain-specific αGDI, shown to alter a subset of RAB GTPases redistribution in cells, are linked to XLID, likely via changes in vesicle traffic in neurons. Here, we show directly that isolated XLID mice astrocytes, devoid of pathologic tissue environment, exhibit vesicle mobility deficits.

Hyperpolarization-activated cyclic nucleotide-gated channels and cAMP-dependent modulation of exocytosis in cultured rat lactotrophs.

Hormone and neurotransmitter release from vesicles is mediated by regulated exocytosis, where an aqueous channel-like structure, termed a fusion pore, is formed. It was recently shown that second messenger cAMP modulates the fusion pore, but the detailed mechanisms remain elusive. In this study, we asked whether the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are activated by cAMP, are involved in the regulation of unitary exocytic events.

Single-vesicle architecture of synaptobrevin2 in astrocytes.

Exocytic transmitter release is regulated by the SNARE complex, which contains a vesicular protein, synaptobrevin2 (Sb2). However, Sb2 vesicular arrangement is unclear. Here we use super-resolution fluorescence microscopy to study the prevalence and distribution of endogenous and exogenous Sb2 in single vesicles of astrocytes, the most abundant glial cells in the brain.

Tick-borne encephalitis virus infects rat astrocytes but does not affect their viability.

Tick-borne encephalitis virus (TBEV) causes one of the most dangerous human neuroinfections in Europe and Asia. To infect neurons it must cross the blood-brain-barrier (BBB), and presumably also cells adjacent to the BBB, such as astrocytes, the most abundant glial cell type. However, the knowledge about the viral infection of glial cells is fragmental.

Astrocytic vesicle mobility in health and disease.

Astrocytes are no longer considered subservient to neurons, and are, instead, now understood to play an active role in brain signaling. The intercellular communication of astrocytes with neurons and other non-neuronal cells involves the exchange of molecules by exocytotic and endocytotic processes through the trafficking of intracellular vesicles. Recent studies of single vesicle mobility in astrocytes have prompted new views of how astrocytes contribute to information processing in nervous tissue.

Regulation of AQP4 surface expression via vesicle mobility in astrocytes.

Aquaporin 4 (AQP4) is the predominant water channel in the brain, expressed mainly in astrocytes and involved in water transport in physiologic and pathologic conditions. Besides the classical isoforms M1 (a) and M23 (c), additional ones may be present at the plasma membrane, such as the recently described AQP4b, d, e, and f. Water permeability regulation by AQP4 isoforms may involve several processes, such as channel conformational changes, the extent and arrangement of channels at the plasma membrane, and the dynamics of channel trafficking to/from the plasma membrane.

Astrocytes negatively regulate neurogenesis through the Jagged1-mediated Notch pathway.

Adult neurogenesis is regulated by a number of cellular players within the neurogenic niche. Astrocytes participate actively in brain development, regulation of the mature central nervous system (CNS), and brain plasticity. They are important regulators of the local environment in adult neurogenic niches through the secretion of diffusible morphogenic factors, such as Wnts.

IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments.

Background: In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-γ (IFN-γ) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking.