Antidepressants act directly on astrocytes: Evidences and functional consequences

Czéh, Boldizsár; Benedetto, Barbara Di

doi:10.1016/j.euroneuro.2012.04.017

Cited by 114 publications

(77 citation statements)

References 191 publications

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“…Likewise, inhibition of astroglial plasmalemmal glutamate transporters also induced anhedonia (Bechtholt-Gompf et al ., 2010). Chronic treatment with antidepressants directly affected astroglia, by increasing expression of receptors and transporters responsible for CNS homeostasis and limiting glutamate release (Czeh and Di Benedetto, 2013; Dong et al ., 2015; Liu et al ., 2015; Ren et al ., 2015). In conclusion, mood disorders are associated with astrodegeneration and astroglial asthenia, which in turn affect brain homeostatic reserve and arguably synaptic transmission.…”

Section: Astroglia In Major Neuropsychiatric Diseasesmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

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Section: Astroglia In Major Neuropsychiatric Diseasesmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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“…Functional changes undergone by reactive astrocytes in response to specific molecular triggers can impact neurons via (1) down-regulation of glutamine synthase associated with reduced inhibitory synaptic currents in local neurons (Ortinski et al 2010), (2) increased expression of xCT (Slc7a11), a cysteine-glutamate transporter associated with increased glutamate signaling, seizures, and excitotoxicity (Jackman et al 2010;Buckingham et al 2011), and (3) changes in the expression of multiple GPCRs and G proteins and calcium signaling evoked by their ligands (Hamby et al 2012). There is increasing evidence for astrocyte participation in complex behaviors including sleep (Halassa and Haydon 2010), pain (Hansen and Malcangio 2013), mood, depression (Halassa and Haydon 2010; Paradise et al 2012;Czeh and Di Benedetto 2013;Martin et al 2013), and certain childhood behavioral disorders with altered synapse development (Stephan et al 2012;Clarke and Barres 2013). Astrocytes are primary targets of cytokines and inflammatory mediators increasingly implicated not only in sickness behaviors, such as social withdrawal, reduced activity, loss of appetite, and cognitive disturbances, but also in certain kinds of sleep disturbances, mood disturbances, major depressive disorders, and CNS developmental disorders (Dantzer et al 2008;Dowlati et al 2010;Irwin and Cole 2011;Jurgens et al 2012;Patterson 2012;Sofroniew 2013).…”

Section: Astrogliosis and Neuronal Function And Behaviormentioning

confidence: 99%

Astrogliosis

Sofroniew¹

2014

Cold Spring Harb Perspect Biol

552

513

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“…The leading mechanism of Wernicke encephalopathy (clinically expressed as Korsakoff syndrome) is directly associated with profound downregulation of astroglial glutamate transporters with ensuing excitotoxic neuronal death [151,152]. Astrocytes therefore are increasingly considered as a legitimate target for cellspecific therapy in various neuropsychiatric conditions [153,154].…”

Section: Neuropathology As a Homeostatic Failure: Central Role For Asmentioning

confidence: 99%

The homeostatic astroglia emerges from evolutionary specialization of neural cells

Verkhratsky

2016

Phil. Trans. R. Soc. B

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Evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed from electrically excitable neuronal networks connected with chemical synapses and non-excitable glial cells that provide for homeostasis and defence. Astrocytes are integrated into neural networks through multipartite synapses; astroglial perisynaptic processes closely enwrap synaptic contacts and control homeostasis of the synaptic cleft, supply neurons with glutamate and GABA obligatory precursor glutamine and contribute to synaptic plasticity, learning and memory. In neuropathology, astrocytes may undergo reactive remodelling or degeneration; to a large extent, astroglial reactions define progression of the pathology and neurological outcome. This article is part of the themed issue 'Evolution brings Ca 2þ and ATP together to control life and death'. Evolution of the nervous system: cellular distribution of functionsThe human brain, which crowns 3.5 billion years of biological evolution, is arguably the most complex structure known to the natural sciences. The brain tissue is composed out of approximately 200 billion neurons and neuroglial cells that are connected by more than 15 trillion electrical and chemical synapses into the networks with extraordinary computing and memory storage capacity-the latter being estimated to reach a petabite mark [1]. High density of electrically excited cells, which rely on constant movement of ions across their membranes, the process requiring ATP in quantity (a single human cortical neuron is claimed to use approximately 4.7 billion ATP molecules per second [2]), makes the brain the major energy consumer in the organism [3]. The high disbursement of ATP stipulates high mitochondrial activity, whereas the oxidative phosphorylation produces reactive oxygen species that have to be scavenged to avoid profound cellular damage. Ion redistribution associated with brain activity has to be controlled, as ion accumulation in the extracellular space seriously affects neuronal excitability. Similarly, the neurotransmitters released in the course of synaptic transmission have to be properly handled to exclude associated neurotoxicity (and glutamate, the main excitatory neurotransmitter, is the most effective endogenous neurotoxin). Finally, these cellular networks and the cells making them are constantly changing their structure, which underlies neural plasticity and learning. These are only a few of the major logistical problems associated with brain function, which are managed surprisingly well in the course of about 100 years of human life. Even more remarkably, the human brain is highly resilient to the passing years and the brain appears as one of the most age-resilient systems of the human body. Indeed, the 40-year-old athlete cannot compete in the sprint with youngsters, whereas a 60-year-old academic has, as a rule, much higher intellectual output than many of his 20-year-old

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Antidepressants act directly on astrocytes: Evidences and functional consequences

Cited by 114 publications

References 191 publications

Translational potential of astrocytes in brain disorders

Translational potential of astrocytes in brain disorders

Astrogliosis

The homeostatic astroglia emerges from evolutionary specialization of neural cells

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