Gliotransmission: Exocytotic release from astrocytes

Parpura, Vladimir; Zorec, Robert

doi:10.1016/j.brainresrev.2009.11.008

Cited by 340 publications

(287 citation statements)

References 97 publications

(138 reference statements)

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“…We did, however, fail to confirm the report that extracellular glutamate is not reduced following intra-hippocampal KYNA infusion (Moroni et al, 2005). This indicates that modulation by KYNA may constitute an additional general mechanism by which astrocytes influence glutamatergic neurotransmission in the brain (Hamilton and Attwell, 2010;Hertz and Zielke, 2004;Parpura and Zorec, 2010).…”

Section: Discussioncontrasting

confidence: 88%

Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory

Pocivavsek

Potter

et al. 2011

Neuropsychopharmacol

146

158

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Kynurenic acid (KYNA), an astrocyte-derived metabolite, antagonizes the a7 nicotinic acetylcholine receptor (a7nAChR) and, possibly, the glycine co-agonist site of the NMDA receptor at endogenous brain concentrations. As both receptors are involved in cognitive processes, KYNA elevations may aggravate, whereas reductions may improve, cognitive functions. We tested this hypothesis in rats by examining the effects of acute up-or downregulation of endogenous KYNA on extracellular glutamate in the hippocampus and on performance in the Morris water maze (MWM). Applied directly by reverse dialysis, KYNA (30-300 nM) reduced, whereas the specific kynurenine aminotransferase-II inhibitor (S)-4-(ethylsulfonyl)benzoylalanine (ESBA; 0.3-3 mM) raised, extracellular glutamate levels in the hippocampus. Co-application of KYNA (100 nM) with ESBA (1 mM) prevented the ESBA-induced glutamate increase. Comparable effects on hippocampal glutamate levels were seen after intra-cerebroventricular (i.c.v.) application of the KYNA precursor kynurenine (1 mM, 10 ml) or ESBA (10 mM, 10 ml), respectively. In separate animals, i.c.v. treatment with kynurenine impaired, whereas i.c.v. ESBA improved, performance in the MWM. I.c.v. co-application of KYNA (10 mM) eliminated the pro-cognitive effects of ESBA. Collectively, these studies show that KYNA serves as an endogenous modulator of extracellular glutamate in the hippocampus and regulates hippocampus-related cognitive function. Our results suggest that pharmacological interventions leading to acute reductions in hippocampal KYNA constitute an effective strategy for cognitive improvement. This approach might be especially useful in the treatment of cognitive deficits in neurological and psychiatric diseases that are associated with increased brain KYNA levels.

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Section: Discussioncontrasting

confidence: 88%

Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory

Pocivavsek

Potter

et al. 2011

Neuropsychopharmacol

146

158

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“…Indeed, astrocytes respond with intracellular calcium elevations to neurotransmitters released from synaptic terminals [14 -18]. These calcium elevations have been shown to stimulate the release of gliotransmitters through different mechanisms [19][20][21][22][23][24], which still remain debated (for recent reviews, see [25][26][27]). …”

Section: Introductionmentioning

confidence: 99%

Astrocytes in endocannabinoid signalling

Navarrete

Díez

Araque

2014

Phil. Trans. R. Soc. B

113

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Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour.

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“…Astrocytes can release several gliotransmitters such as glutamate, g-aminobutyric acid, D-serine, neuropeptides, and ATP in a calcium-dependent manner (Parpura & Zorec 2010). Astrocytes release D-serine at glutamatergic synapses where it then acts as a co-agonist for N-methyl-D-aspartic acid receptors (Henneberger et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Astrocytes: new targets of melanocortin 4 receptor actions

Caruso¹,

Carniglia²,

Durand³

et al. 2013

Journal of Molecular Endocrinology

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Astrocytes exert a wide variety of functions with paramount importance in brain physiology. After injury or infection, astrocytes become reactive and they respond by producing a variety of inflammatory mediators that help maintain brain homeostasis. Loss of astrocyte functions as well as their excessive activation can contribute to disease processes; thus, it is important to modulate reactive astrocyte response. Melanocortins are peptides with well-recognized anti-inflammatory and neuroprotective activity. Although melanocortin efficacy was shown in systemic models of inflammatory disease, mechanisms involved in their effects have not yet been fully elucidated. Central anti-inflammatory effects of melanocortins and their mechanisms are even less well known, and, in particular, the effects of melanocortins in glial cells are poorly understood. Of the five known melanocortin receptors (MCRs), only subtype 4 is present in astrocytes. MC4R has been shown to mediate melanocortin effects on energy homeostasis, reproduction, inflammation, and neuroprotection and, recently, to modulate astrocyte functions. In this review, we will describe MC4R involvement in anti-inflammatory, anorexigenic, and anti-apoptotic effects of melanocortins in the brain. We will highlight MC4R action in astrocytes and discuss their possible mechanisms of action. Melanocortin effects on astrocytes provide a new means of treating inflammation, obesity, and neurodegeneration, making them attractive targets for therapeutic interventions in the CNS.

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Gliotransmission: Exocytotic release from astrocytes

Cited by 340 publications

References 97 publications

Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory

Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory

Astrocytes in endocannabinoid signalling

Astrocytes: new targets of melanocortin 4 receptor actions

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