Dopamine release regulation by astrocytes during cerebral ischemia
Brain ischemia triggers excessive release of neurotransmitters that mediate neuronal damage following ischemic injury. The striatum is one of the areas most sensitive to ischemia. Release of dopamine (DA) from ischemic neurons is neurotoxic and directly contributes to the cell death in affected area...
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2013-10-01
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doaj-956b12fabb0e4b1a90eb8a6eff9a76ee2021-03-22T12:40:06ZengElsevierNeurobiology of Disease1095-953X2013-10-0158231241Dopamine release regulation by astrocytes during cerebral ischemiaIdaira Oliva0Miriam Fernández1Eduardo D. Martín2Laboratory of Neurophysiology and Synaptic Plasticity, Albacete Science and Technology Park (PCYTA), Institute for Research in Neurological Disabilities (IDINE), University of Castilla-La Mancha, Albacete, SpainLaboratory of Neurophysiology and Synaptic Plasticity, Albacete Science and Technology Park (PCYTA), Institute for Research in Neurological Disabilities (IDINE), University of Castilla-La Mancha, Albacete, SpainCorresponding author at: PCYTA, IDINE, University of Castilla-La Mancha, Almansa 14, 02006 Albacete, Spain. Fax: +34 967 599 360.; Laboratory of Neurophysiology and Synaptic Plasticity, Albacete Science and Technology Park (PCYTA), Institute for Research in Neurological Disabilities (IDINE), University of Castilla-La Mancha, Albacete, SpainBrain ischemia triggers excessive release of neurotransmitters that mediate neuronal damage following ischemic injury. The striatum is one of the areas most sensitive to ischemia. Release of dopamine (DA) from ischemic neurons is neurotoxic and directly contributes to the cell death in affected areas. Astrocytes are known to be critically involved in the physiopathology of cerebrovascular disease. However, their response to ischemia and their role in neuroprotection in striatum are not completely understood. In this study, we used an in vitro model to evaluate the mechanisms of ischemia-induced DA release, and to study whether astrocytes modulate the release of DA in response to short-term ischemic conditions. Using slices of adult mouse brain exposed to oxygen and glucose deprivation (OGD), we measured the OGD-evoked DA efflux using fast cyclic voltammetry and also assessed metabolic impairment by 2,3,5-triphenyltetrazolium chloride (TTC) and tissue viability by propidium iodide (PI) staining. Our data indicate that ischemia induces massive release of DA by dual mechanisms: one which operates via vesicular exocytosis and is action potential dependent and another involving reverse transport by the dopamine transporter (DAT). Simultaneous blockade of astrocyte glutamate transporters and DAT prevented the massive release of dopamine and reduced the brain tissue damage. The present results provide the first experimental evidence that astrocytes function as a key cellular element of ischemia-induced DA release in striatum, constituting a novel and promising therapeutic target in ischemia.http://www.sciencedirect.com/science/article/pii/S0969996113001745StriatumGlutamate transportersFast-scan cyclic voltammetryDopamine transportersExcitotoxicity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Idaira Oliva Miriam Fernández Eduardo D. Martín |
spellingShingle |
Idaira Oliva Miriam Fernández Eduardo D. Martín Dopamine release regulation by astrocytes during cerebral ischemia Neurobiology of Disease Striatum Glutamate transporters Fast-scan cyclic voltammetry Dopamine transporters Excitotoxicity |
author_facet |
Idaira Oliva Miriam Fernández Eduardo D. Martín |
author_sort |
Idaira Oliva |
title |
Dopamine release regulation by astrocytes during cerebral ischemia |
title_short |
Dopamine release regulation by astrocytes during cerebral ischemia |
title_full |
Dopamine release regulation by astrocytes during cerebral ischemia |
title_fullStr |
Dopamine release regulation by astrocytes during cerebral ischemia |
title_full_unstemmed |
Dopamine release regulation by astrocytes during cerebral ischemia |
title_sort |
dopamine release regulation by astrocytes during cerebral ischemia |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2013-10-01 |
description |
Brain ischemia triggers excessive release of neurotransmitters that mediate neuronal damage following ischemic injury. The striatum is one of the areas most sensitive to ischemia. Release of dopamine (DA) from ischemic neurons is neurotoxic and directly contributes to the cell death in affected areas. Astrocytes are known to be critically involved in the physiopathology of cerebrovascular disease. However, their response to ischemia and their role in neuroprotection in striatum are not completely understood. In this study, we used an in vitro model to evaluate the mechanisms of ischemia-induced DA release, and to study whether astrocytes modulate the release of DA in response to short-term ischemic conditions. Using slices of adult mouse brain exposed to oxygen and glucose deprivation (OGD), we measured the OGD-evoked DA efflux using fast cyclic voltammetry and also assessed metabolic impairment by 2,3,5-triphenyltetrazolium chloride (TTC) and tissue viability by propidium iodide (PI) staining. Our data indicate that ischemia induces massive release of DA by dual mechanisms: one which operates via vesicular exocytosis and is action potential dependent and another involving reverse transport by the dopamine transporter (DAT). Simultaneous blockade of astrocyte glutamate transporters and DAT prevented the massive release of dopamine and reduced the brain tissue damage. The present results provide the first experimental evidence that astrocytes function as a key cellular element of ischemia-induced DA release in striatum, constituting a novel and promising therapeutic target in ischemia. |
topic |
Striatum Glutamate transporters Fast-scan cyclic voltammetry Dopamine transporters Excitotoxicity |
url |
http://www.sciencedirect.com/science/article/pii/S0969996113001745 |
work_keys_str_mv |
AT idairaoliva dopaminereleaseregulationbyastrocytesduringcerebralischemia AT miriamfernandez dopaminereleaseregulationbyastrocytesduringcerebralischemia AT eduardodmartin dopaminereleaseregulationbyastrocytesduringcerebralischemia |
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