Calcium signaling in astrocytes and gliotransmitter release

Frontiers in Synaptic Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 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.

Language: Английский

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Foundations and implications of astrocyte heterogeneity during brain development and disease

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 45(9), P. 692 - 703

Published: July 23, 2022

Language: Английский

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Astrocyte heterogeneity and interactions with local neural circuits

Essays in Biochemistry, Journal Year: 2023, Volume and Issue: 67(1), P. 93 - 106

Published: Feb. 7, 2023

Astrocytes are ubiquitous within the central nervous system (CNS). These cells possess many individual processes which extend out into neuropil, where they interact with a variety of other cell types, including neurons at synapses. now known to be active players in all aspects synaptic life cycle, synapse formation and elimination, maturation, maintenance homeostasis modulation transmission. Traditionally, astrocytes have been studied as homogeneous group cells. However, recent studies uncovered surprising degree heterogeneity their development function, suggesting that may matched support local circuits. Hence, better understanding astrocyte its implications needed understand brain function.

Language: Английский

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Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 9067 - 9067

Published: May 22, 2023

Alzheimer’s disease (AD) is a chronic neurodegenerative and the most frequent cause of progressive dementia in senior adults. It characterized by memory loss cognitive impairment secondary to cholinergic dysfunction N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed amyloid-β (Aβ), selective neurodegeneration are anatomopathological hallmarks this disease. The dysregulation calcium may be present all stages AD, it associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, neuroinflammation. Although cytosolic alterations AD not completely elucidated, some calcium-permeable channels, transporters, pumps, receptors have been shown involved at neuronal glial levels. In particular, relationship between glutamatergic NMDA receptor (NMDAR) activity amyloidosis has widely documented. Other mechanisms dyshomeostasis include activation L-type voltage-dependent transient potential ryanodine receptors, among many others. This review aims update calcium-dysregulation discuss targets molecules therapeutic based on their modulation.

Language: Английский

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Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 22, 2023

Calcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present longitudinal study the PS2APP mouse model of Alzheimer's disease (AD) linking astrocyte Ca2+ hypoactivity to memory loss. At onset plaque deposition, somatosensory cortical AD female mice exhibit drastic reduction signaling, closely associated with decreased endoplasmic reticulum concentration reduced expression sensor STIM1. In parallel, astrocyte-dependent long-term declines circuitry, anticipating specific tactile Notably, show both signaling are fully recovered by selective STIM1 overexpression astrocytes. Our data unveil neocortical as functional hallmark early stages indicate astrocytic target rescue deficits.

Language: Английский

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Astrocyte Mitochondria Are a Sensitive Target of PCB52 and its Human-Relevant Metabolites

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(15), P. 2729 - 2740

Published: July 2, 2024

Polychlorinated biphenyls (PCBs) are industrial chemicals that ubiquitously found in the environment. Exposure to these compounds has been associated with neurotoxic outcomes; however, underlying mechanisms for such outcomes remain be fully understood. Recent studies have shown astrocytes, most abundant glial cell type brain, susceptible PCB exposure as well human-relevant metabolites of PCBs. Astrocytes critical maintaining healthy brain function due their unique functional attributes and positioning within neuronal networks brain. In this study, we assessed toxicity PCB52, one abundantly congeners outdoor indoor air, two its metabolites, on astrocyte mitochondria. We exposed C6 cells, an line, PCB52 or all showed increased galactose-containing media compared glucose-containing media, indicating involvement mitochondria observed toxicity. Additionally, also oxidative stress upon metabolites. All three caused a loss mitochondrial membrane potential, distinct changes structure, impaired function. The hydroxylated metabolite 4-OH-PCB52 likely functions uncoupler This is first study report adverse effects structure astrocytes.

Language: Английский

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Side-by-side comparison of the effects of Gq- and Gi-DREADD-mediated astrocyte modulation on intracellular calcium dynamics and synaptic plasticity in the hippocampal CA1

Molecular Brain, Journal Year: 2021, Volume and Issue: 14(1)

Published: Sept. 20, 2021

Abstract Astrocytes express a plethora of G protein-coupled receptors (GPCRs) that are crucial for shaping synaptic activity. Upon GPCR activation, astrocytes can respond with transient variations in intracellular Ca 2+ . In addition, -dependent and/or -independent release gliotransmitters occur, allowing them to engage bidirectional neuron-astrocyte communication. The development designer exclusively activated by drugs (DREADDs) has facilitated many new discoveries on the roles both physiological and pathological conditions. They an excellent tool, as they target endogenous GPCR-mediated signal transduction pathways specifically astrocytes. With increasing interest accumulating research this topic, several discrepancies astrocytic signalling astrocyte-mediated effects plasticity have emerged, preventing clear-cut consensus about downstream DREADDs present study, we performed side-by-side evaluation bath application DREADD agonist, clozapine-N-oxide (10 µM), Gq- Gi-DREADD activation mouse CA1 hippocampal doing so, aimed avoid confounding factors, such differences experimental procedures, directly compare actions dynamics acute slices. We used adeno-associated viral vector approach transduce dorsal hippocampi male, 8-week-old C57BL6/J mice, drive expression either Gq-DREADD or A lacking construct was generate controls. Here, show agonism Gq-DREADDs, but not Gi-DREADDs, induced consistent increases spontaneous events. Moreover, demonstrate well Gi-DREADD-mediated induces long-lasting potentiation Schaffer collateral pathway absence high frequency stimulus. report first time is sufficient elicit de novo potentiation. Our data Gq Gi drives through mechanisms, respectively.

Language: Английский

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Targetability of the neurovascular unit in inflammatory diseases of the central nervous system

Immunological Reviews, Journal Year: 2022, Volume and Issue: 311(1), P. 39 - 49

Published: July 31, 2022

Summary The blood–brain barrier (BBB) is a selectively permeable separating the periphery from central nervous system (CNS). BBB restricts flow of most material into and out CNS, including many drugs that could be used as potent therapies. permeability modulated by several cells are collectively called neurovascular unit (NVU). NVU consists specialized CNS endothelial (ECs), pericytes, astrocytes, microglia, neurons. ECs maintain complex “seal” via tight junctions, forming BBB; breakdown these junctions leads to disruption. Pericytes control vascular within capillaries help basal lamina. Astrocytes much has moved beyond EC layer can form secondary under inflammatory conditions. Microglia survey border for noxious material. Neuronal activity also plays role in maintenance BBB. Since neurons all able modulate BBB, understating contributions each member will potentially uncover novel effective methods delivery neurotherapies CNS.

Language: Английский

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Striatal astrocytic A2A-D2 receptor-receptor interactions and their role in neuropsychiatric disorders

Neuropharmacology, Journal Year: 2023, Volume and Issue: 237, P. 109636 - 109636

Published: June 15, 2023

It is now generally accepted that astrocytes are active players in synaptic transmission, so a neurocentric perspective of the integrative signal communication central nervous system shifting towards neuro-astrocentric perspective. Astrocytes respond to activity, release chemical signals (gliotransmitters) and express neurotransmitter receptors (G protein-coupled ionotropic receptors), thus behaving as co-actors with neurons system. The ability G physically interact through heteromerization, forming heteromers receptor mosaics new distinct recognition transduction pathways, has been intensively studied at neuronal plasma membrane, changed view One best-known examples receptor-receptor interaction relevant consequences for both physiological pharmacological points view, given by adenosine A2A dopamine D2 on membrane striatal neurons. Here we review evidence native can heteromerization well. Astrocytic A2A-D2 were found able control glutamate from astrocyte processes. processes discussed far their potential relevance glutamatergic transmission striatum concerned, including roles dysregulation pathological conditions schizophrenia or Parkinson's disease.

Language: Английский

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Comparative assessment of the effects of DREADDs and endogenously expressed GPCRs in hippocampal astrocytes on synaptic activity and memory

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 27, 2023

Designer Receptors Exclusively Activated by Drugs (DREADDs) have proven themselves as one of the key in vivo techniques modern neuroscience, allowing for unprecedented access to cellular manipulations living animals. With respect astrocyte research, DREADDs become a popular method examine functional aspects activity, particularly G-protein coupled receptor (GPCR)-mediated intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) dynamics. this it has possible directly link physiological astrocytic function cognitive processes such memory. As result, multitude studies explored impact DREADD activation astrocytes on synaptic activity However, emergence varying results prompts us reconsider degree which expressed accurately mimic endogenous GPCR activity. Here we compare major downstream signaling mechanisms, synaptic, behavioral effects stimulating Gq-, Gs-, Gi-DREADDs hippocampal adult mice those endogenously GPCRs.

Language: Английский

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