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Mechanical Stretch Disrupts Calcium Dynamics and Redistributes Piezo1 in Human Astrocytes.

PURPOSE: Astrocytes regulate the activity of nearby neurons so disruption of astrocyte calcium dynamics by traumatic brain injury (TBI) could have profound consequences for neural network activity in the brain. This study aimed to define how mechanical stretch injury alters calcium signaling, mitochondrial membrane potential, and mechanosensitive ion channel organization in human induced pluripotent stem cell (hiPSC)-derived astrocytes. METHODS: Human iPSC-derived astrocytes were subjected to controlled two-dimensional stretch injury across multiple severities. Live-cell calcium and mitochond…

Aberrant Potassium Handling by Astrocytes and Epileptic Seizures: A Synthetic Update.

Excessive extracellular accumulation of K+ plays a key role in the induction and propagation of seizures associated with temporal lobe epilepsy (TLE), and astrocytes are largely responsible for K+ clearance from the extracellular space. Here, we review the TLE-related changes in the content and/or activity of proteins contributing to K+ transport across the astrocytic cell membranes. Seizures, whether genetic or acquired, are linked with decreased expression and/or mislocalization of the two key astroglia-specific drivers of K+ uptake: the inward rectifying potassium channel Kir4.1 and its spa…

Hopx(+) optic nerve head-astrocytes counter neuronal stress and glaucoma damage.

Retinal ganglion cell (RGC) axons form the optic nerve (ON). Numerous age-related ON diseases, including glaucoma, the second most common cause of worldwide blindness, result from multiple RGC stressors. Nearly all ON astrocytes in the optic nerve head (ONH): the junctional region between the ON and the retina in young-adult rodents expresses the homeodomain only (Hopx) protein. Hopx(+) ONH astrocytes are depleted during aging. ONH primary cultures which include Hopx(+) astrocytes secrete extracellular vesicles (ONH-EVs) which selectively enhance RGC survival and neurite extension in culture, …

Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration.

Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkins … rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astroc …

Human Endogenous Retrovirus K in Astrocytes Is Altered in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative movement disease. Human endogenous retroviruses (HERVs) are provir … y Unified Parkinson's Disease Rating Scale Part III. RESULTS: HERV-K is predominantly expressed in astrocytes and colocalized with astrocytic GFAP, with decreased expression of both HERV-K and GFAP in PD brain compared with controls. Consistent with this, HERV-K levels were decreased in PD blood compared with controls and were correlated to blood GFAP level …

Chemogenetic Control of Striatal Astrocytes Improves Parkinsonian Motor Deficits in Mice.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source for striatal neuromodulation. There is substantial evidence for norepinephrine-mediated recruitment of cortical astrocyte activity during movement and locomotion. However, it is unclear how astrocytes in the striatum, a region devoid of norepinephrine neuromodulatory inputs, respond during locomotion. Moreover, it remains unknown how dopamine loss af…

Astrocytes upregulate interleukin-15 in response to neuroinflammation during Alzheimer's disease.

BackgroundInterleukin (IL)-15 is a pleiotropic cytokine linked to cognition that is increased in the cerebrospinal fluid of Alzheimer's dise … sultsIn the prefrontal cortex of AD patients, we observed increased IL-15 colocalization with GFAP+ astrocytes (p = 0.0181) near Aβ plaques and demonstrate that astrocytes, but not neurons, upregulate IL-15 in response to interferon-γ and tumor necrosis factor-α in vitro (p = 0.0003 and p < 0.0001, respectively). We also show that neurons express increased I …

Brain Synapses: Neurons, Astrocytes, and Extracellular Vesicles in Health and Diseases.

Synapses, abundant in the brain, are structures needed for life. Our Introduction, based on the forms of such structures published few decad … re- and post-synaptic thickness remains unchanged. In additional responses, neurons co-operate with astrocytes and extracellular vesicles (EVs), the latter dependent on extracellular and intracellular spaces. Astrocyte and microglia cells and/or EV secretions induce neurons by various effects including traveling changes. Pre-synaptic responses are defined as …

A Novel Serum-Free Triculture Model of Glioblastoma, Astrocytes, and Macrophages.

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. While in vitro patient-derived xenografts (PDX) lines are useful for studying GBM, they often exclude astrocytes and macrophages, which contribute significantly to tumor growth, invasion, and chemoradioresistance. Integrating these cells into tumor models is difficult due to their need for serum, which triggers GBM-PDX lines to lose their stem-like properties. The aim of this study was to develop a serum-free triculture model of GBM-PDX lines, normal human astrocytes (NHAs), and macrophages. Serum-free media altern…

Knockdown of PDPN in astrocytes reduces hippocampal inflammation in T2DM mice.

AIMS: Individuals with type 2 diabetes mellitus (T2DM) are at-risk for developing vascular dementia (VaD). Hyperglycemia leads to the activation of astrocytes. These activated cells produce proinflammatory mediators like cytokines or chemokines, that cause cerebrovascular damage. Previous sequencing showed Pdpn's high expression in activated stellate cells and possible inflammation involvement. Our study aims to reveal its role in T2DM-induced hippocampal inflammation in VaD. METHODS: Firstly, we will validate the expression of the Pdpn gene in T2DM astrocytes via qPCR and Western blot. Subse…

pH Sensor-Based Engulfment Assays to Measure Phagocytic Activity of Astrocytes.

Astrocytes play a crucial role in eliminating unnecessary synapses, neural debris, and pathogenic proteins such as amyloid β plaque through phagocytosis. Emerging evidence suggests that the phagocytic roles of astrocytes are critical for remodeling our neural circuits during development as well as maintaining brain homeostasis in adulthood. Moreover, abnormal astrocytic phagocytosis can have direct implications for the initiation and progression of various brain disorders. However, classical methods for identifying phagocytic events in the brains have utilized immunostaining-based and/or elect…

Astrocytes Mediate Psychostimulant-Induced Alterations of Spike-Timing Dependent Synaptic Plasticity.

At cellular and circuit levels, drug addiction is considered a dysregulation of synaptic plasticity. In addition, dysfunction of the glutamate transporter 1 (GLT-1) in the nucleus accumbens (NAc) has also been proposed as a mechanism underlying drug addiction. However, the cellular and synaptic impact of GLT-1 alterations in the NAc remain unclear. Here we show in the NAc that 10 days withdraw after 5 days treatment with cocaine or amphetamine decreases GLT-1 expression in astrocytes, which results in the prolongation of the excitatory postsynaptic potential (EPSP) decay kinetics in D1 recepto…

Rostral ventromedial medulla astrocytes regulate chronic itch and anxiety-related behaviors.

Itch (pruritus), a maladaptive and debilitating cutaneous symptom, is commonly associated with many skin conditions; however, the available therapies with sufficient efficacy are lacking. The role of astrocytes in the rostral ventromedial medulla (RVM), a crucial brain region in the descending pain modulation system, in chronic itch remains uncertain. In this study, we examined the chronic itch behavior and itch-related anxiety behavior in the diphenylcyclopripenone (DCP)-induced contact dermatitis mice, and also observed the activation of astrocytes in the RVM in the DCP mice. Reducing calciu…

Astrocytes in the mouse brain respond bilaterally to unilateral retinal neurodegeneration.

Glaucomatous optic neuropathy, or glaucoma, is the world's primary cause of irreversible blindness. Glaucoma is comorbid with other neurodeg … ic tract are the first to lose transport function. Although degeneration was induced in one retina, astrocytes in both brain hemispheres responded to transport loss in a retinotopic pattern that mirrored the degenerating RGCs. A subpopulation of these astrocytes in contact with large descending blood vessels were immunopositive for LCN2, a marker associated …

На производство цитокина и химокина астроцитами влияет цистатин С.

Астроциты играют важную роль в гомеостазисе как структурные и функциональные компоненты трехстороннего синапсового сигнала, целостности мозгового барьера и буферизации нейротрансмиттера. Однако эти глиа могут стать реактивными в таких болезнях, как множественный склероз (MS), где они могут усугублять провоспалительную среду путем вербовки и поощрения активности иммунных клеток путем секреции цитокинов и хемокинов и, возможно, представления антигенов. Неполно известны молекулярные регуляторы активации астроцитов. Изменяющиеся уровни Cst3 mRNA и Cystatin C (CysC) были зарегистрированы в различны

Совпадение в аннотации оригинала
Astrocytes play essential roles during homeostasis as structural and functional components of tripartite synapse signaling, blood brain barrier integrity, and neurotransmitter buffering. However, these glia can become reactive in diseases such as multiple sclerosis (MS), where they can exacerbate pro-inflammatory environments by recruiting and promoting immu…

Metabolic Reprogramming of Astrocytes in Pathological Conditions: Implications for Neurodegenerative Diseases.

Astrocytes play a pivotal role in maintaining brain energy homeostasis, supporting neuronal function through glycolysis and lipid metabolism. This review explores the metabolic intricacies of astrocytes in both physiological and pathological conditions, highlighting their adaptive plasticity and diverse functions. Under normal conditions, astrocytes modulate synaptic activity, recycle neurotransmitters, and maintain the blood-brain barrier, ensuring a balanced energy supply and protection against oxidative stress. However, in response to central nervous system pathologies such as neurotrauma, …

Mitochondrial Dysfunction of Astrocytes Mediates Lipid Accumulation in Temporal Lobe Epilepsy.

Lipid-accumulated reactive astrocytes (LARAs) have recently been confirmed to be a pivotal cell type present in temporal lobe epilepsy (TLE) lesions. These cells not only induce anomalous lipid accumulation within the epileptic foci but also decrease the seizure threshold by employing upregulated activation of the adenosine A2A receptor (A2AR). Furthermore, disturbances in mitochondrial oxidative phosphorylation (OxPhos) have been noted as significant drivers of lipid accumulation in astrocytes. Moreover, the deficiency of OxPhos in astrocytes can induce severe neuroinflammation, which can wor…

Metabolic preferences of astrocytes: Functional metabolic mapping reveals butyrate outcompetes acetate.

Disruptions to the gut-brain-axis have been linked to neurodegenerative disorders. Of these disruptions, reductions in the levels of short-chain fatty acids (SCFAs), like butyrate, have been observed in mouse models of Alzheimer's disease (AD). Butyrate supplementation in mice has shown promise in reducing neuroinflammation, amyloid-β accumulation, and enhancing memory. However, the underlying mechanisms remain unclear. To address this, we investigated the impact of butyrate on energy metabolism in mouse brain slices, primary cultures of astrocytes and neurons and in-vivo by dynamic isotope la…

Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.

Memory refers to the imprint accumulated in the brain by life experiences and represents the basis for humans to engage in advanced psychological activities such as thinking and imagination. Previously, research activities focused on memory have always targeted neurons. However, in addition to neurons, astrocytes are also involved in the encoding, consolidation, and extinction of memory. In particular, astrocytes are known to affect the recruitment and function of neurons at the level of local synapses and brain networks. Moreover, the involvement of astrocytes in memory and memory-related dis…

Brainstem astrocytes regulate breathing and may affect arousal state in rats.

Variations in arousal levels can impact respiratory patterns. The mechanisms by which breathing behaviors can influence arousal state is not fully understood. In this study, we investigated the role of astrocytes in the preBötzinger complex (preBötC) in modulating arousal states via breathing in adult conscious rats. Using viral vector tools, we selectively interfered with astrocytic signaling in the preBötC. Rats with inhibited astrocytic signaling exhibited slower breathing rates and behaviors indicative of a calmer state, whereas enhanced purinergic signaling in preBötC astrocytes led to fa…