An astroglial basis of major depressive disorder? An overview

Glia, Год журнала: 2017, Номер 65(8), С. 1227 - 1250

Опубликована: Март 20, 2017

Abstract Depression is a chronic, recurring, and serious mood disorder that afflicts up to 20% of the global population. The monoamine hypothesis has dominated our understanding pharmacotherapy depression for more than half century; however, pathophysiology pathogenesis major lagged far behind. Astrocytes are most abundant versatile cells in brain, participating most, if not all, brain functions as both passive housekeeper an active player. Mounting evidence from clinical, preclinical post‐mortem studies revealed decrease number or density astrocytes morphological functional astroglial atrophy patients with depressive (MDD) animal models depression. Furthermore, currently available antidepressant treatments at least partially exert their therapeutic effects on astrocytes. More importantly, dysfunctional lead depressive‐like phenotypes animals. Together, current point pathology potential root cause MDD. Thus, shift neuron‐centric astrocyte‐centric MDD gained increasing attention during past two decades. Here we will summarize supporting disease astrocyte highlight previous promising strategies directly target development novel treatments.

Язык: Английский

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G_i/o protein‐coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission

Glia, Год журнала: 2019, Номер 67(6), С. 1076 - 1093

Опубликована: Фев. 23, 2019

Abstract G protein‐coupled receptors (GPCRs) play key roles in intercellular signaling the brain. Their effects on cellular function have been largely studied neurons, but their functional consequences astrocytes are less known. Using both endogenous and chemogenetic approaches with DREADDs, we investigated of q i/o GPCR activation astroglial Ca 2+ ‐based activity, gliotransmitter release, neuronal electrical activity. We found that while led to neurons astrocytes, inhibition astrocytes. Astroglial by either or protein‐mediated stimulated which increased excitability. Additionally, DREADDs vivo astrocyte activity modified network Present results reveal additional complexity excitatory inhibitory neurotransmitters astroglia‐neuron operation brain function.

Язык: Английский

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G-Protein-Coupled Receptors in Astrocyte–Neuron Communication

Neuroscience, Год журнала: 2020, Номер 456, С. 71 - 84

Опубликована: Март 26, 2020

Язык: Английский

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Functional Roles of Astrocyte Calcium Elevations: From Synapses to Behavior

Frontiers in Cellular Neuroscience, Год журнала: 2018, Номер 11

Опубликована: Янв. 16, 2018

Astrocytes are fundamental players in the regulation of synaptic transmission and plasticity. They display unique morphological phenotypical features that allow to monitor dynamically respond changes. One hallmarks astrocytic response is generation calcium elevations, which further affect downstream cellular processes. Technical advances field have allowed spatially temporally quantify qualify these elevations. However, impact on brain function remains poorly understood. In this review, we discuss evidences functional heterogeneous events several regions, their consequences synapses, circuits behavior.

Язык: Английский

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Multiple Lines of Evidence Indicate That Gliotransmission Does Not Occur under Physiological Conditions

Journal of Neuroscience, Год журнала: 2018, Номер 38(1), С. 3 - 13

Опубликована: Янв. 3, 2018

A major controversy persists within the field of glial biology concerning whether or not, under physiological conditions, neuronal activity leads to Ca2+-dependent release neurotransmitters from astrocytes, a phenomenon known as gliotransmission. Our perspective is that, while we and others can apply techniques cause gliotransmission, there considerable evidence gathered using astrocyte-specific more approaches which suggests that gliotransmission pharmacological rather than process. Approaches providing against include stimulation Gq-GPCRs expressed only in well removal primary proposed source astrocyte Ca2+ responsible for These contrast with those supportive mechanical stimulation, strong astrocytic depolarization whole-cell patch-clamp optogenetics, uncaging IP3, chelating BAPTA, nonspecific bath application agonists receptors by multitude cell types. are not subtle therefore recent suggestions requires very specific delicate temporal spatial requirements. Other evidence, including lack propagating waves between astrocytes healthy tissue, expression vesicular machinery, demise d-serine hypothesis, provides additional Overall, data suggest province neurons, intact brain conditions.Dual Perspectives Companion Paper: Gliotransmission: Beyond Black-and-White, Iaroslav Savtchouk Andrea Volterra.

Язык: Английский

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