Ammonia triggers exocytotic release of <scp>L</scp>‐glutamate from cultured rat astrocytes

Görg, Boris; Morwinsky, Anke; Keitel, Verena; Qvartskhava, Natalia; Schrör, Karsten; Häussinger, Dieter

doi:10.1002/glia.20955

Cited by 53 publications

(10 citation statements)

References 63 publications

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“…However, this is rather an overly simplistic and speculative view. The strong experimental support for contribution of VRAC is currently lacking and other mechanisms for neurotransmitter release have also been proposed (see for example [69] and review [137]).…”

Section: Common and Unique Roles Of Vrac Within The Brainmentioning

confidence: 99%

Volume-regulated anion channel—a frenemy within the brain

Mongin

2015

Pflugers Arch - Eur J Physiol

115

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Volume regulated anion channel (VRAC) is a ubiquitously expressed yet highly enigmatic member of the superfamily of chloride/anion channels. It is activated by cellular swelling and mediates regulatory cell volume decrease in a majority of vertebrate cells, including those in the central nervous system (CNS). In the brain, besides its crucial role in cellular volume regulation, VRAC is thought to play a part in cell proliferation, apoptosis, migration, and release of physiologically active molecules. Although these roles are not exclusive to the CNS, the relative significance of VRAC in the brain is amplified by several unique aspects of its physiology. One important example is contribution of VRAC to release of the excitatory amino acid neurotransmitters, glutamate and aspartate. This latter process is thought to have impact on both normal brain functioning (such as astrocyte-neuron signaling) and neuropathology (via promoting the excitotoxic death of neuronal cells in stroke and traumatic brain injury). In spite of much work in the field the molecular nature of VRAC remained unknown until less than two years ago. Two pioneer publications identified VRAC as the hetero-hexamer formed by the leucine-rich repeat-containing 8 (LRRC8) proteins. These findings galvanized the field and are likely to result in dramatic revisions to our understanding of the place and role of VRAC in the brain, as well as other organs and tissues. The present review briefly recapitulates critical findings in the CNS, and focuses on anticipated impact on the LRRC8 discovery on further progress in neuroscience research.

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Section: Common and Unique Roles Of Vrac Within The Brainmentioning

confidence: 99%

Volume-regulated anion channel—a frenemy within the brain

Mongin

2015

Pflugers Arch - Eur J Physiol

115

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“…Recent observations demonstrated that in conditions of increased ammonium astrocytes rapidly undergo functional remodeling which severely compromises their homeostatic capabilities. This is represented by: (i) failure in K + buffering due to (at least in part) decreased expression of astroglial K ir 4.1 mediated through N-methyl D-aspartate (NMDA) type of glutamate receptors (Obara-Michlewska et al ., 2014; Rangroo Thrane et al ., 2013); (ii) aberrant astroglial Ca 2+ signaling and Ca 2+ homoeostasis due to an increase in expression of voltage-gated Ca 2+ channels and Ca 2+ -permeable transient receptor potential (TRP) channels as well as in abnormal Ca 2+ release from intracellular stores (Haack et al ., 2014; Liang et al ., 2014; Wang et al ., 2015); (iii) aberrant Ca 2+ signals trigger exocytotic astroglial glutamate release which may add to excitotoxic damage of the brain (Gorg et al ., 2010; Montana et al ., 2014); and (iv) massive pathological elevations in cytosolic Na + concentration and compromised H + transport which leads to abnormalities in pH regulation (Kelly et al ., 2009; Kelly and Rose, 2010). This astroglial remodeling may fundamentally contribute to the hyperammonemia damage.…”

Section: Toxic Damage To the Brainmentioning

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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“…Peripheral organ damage can lead to increases in circulating and brain ammonia concentrations through increases in brain glutamate (Chan et al, 2000; Gorg et al, 2010; Halpin et al, 2014). Ammonia can also induce oxidative stress via superoxide and nitric oxide production as well as through decreases in antioxidant enzymes (Kosenko et al, 1997a,b).…”

Section: Meth-induced Bbb Damagementioning

confidence: 99%

Methamphetamine effects on blood-brain barrier structure and function

Northrop¹

2015

Front. Neurosci.

103

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Methamphetamine (Meth) is a widely abuse psychostimulant. Traditionally, studies have focused on the neurotoxic effects of Meth on monoaminergic neurotransmitter terminals. Recently, both in vitro and in vivo studies have investigated the effects of Meth on the BBB and found that Meth produces a decrease in BBB structural proteins and an increase in BBB permeability to various molecules. Moreover, preclinical studies are validated by clinical studies in which human Meth users have increased concentrations of toxins in the brain. Therefore, this review will focus on the structural and functional disruption of the BBB caused by Meth and the mechanisms that contribute to Meth-induced BBB disruption. The review will reveal that the mechanisms by which Meth damages dopamine and serotonin terminals are similar to the mechanisms by which the blood-brain barrier (BBB) is damaged. Furthermore, this review will cover the factors that are known to potentiate the effects of Meth (McCann et al., 1998) on the BBB, such as stress and HIV, both of which are co-morbid conditions associated with Meth abuse. Overall, the goal of this review is to demonstrate that the scope of damage produced by Meth goes beyond damage to monoaminergic neurotransmitter systems to include BBB disruption as well as provide a rationale for investigating therapeutics to treat Meth-induced BBB disruption. Since a breach of the BBB can have a multitude of consequences, therapies directed toward the treatment of BBB disruption may help to ameliorate the long-term neurodegeneration and cognitive deficits produced by Meth and possibly even Meth addiction.

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Ammonia triggers exocytotic release of L‐glutamate from cultured rat astrocytes

Cited by 53 publications

References 63 publications

Volume-regulated anion channel—a frenemy within the brain

Volume-regulated anion channel—a frenemy within the brain

Translational potential of astrocytes in brain disorders

Methamphetamine effects on blood-brain barrier structure and function

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