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Connexin 43 hemichannels and pannexin-1 channels contribute to the α-synuclein-induced dysfunction and death of astrocytes

dc.contributor.authorDíaz E.F.
dc.contributor.authorLabra V.C.
dc.contributor.authorAlvear T.F.
dc.contributor.authorMellado L.A.
dc.contributor.authorInostroza C.A.
dc.contributor.authorOyarzún J.E.
dc.contributor.authorSalgado N.
dc.contributor.authorQuintanilla R.A.
dc.contributor.authorOrellana J.A.
dc.date.accessioned2020-09-02T22:16:49Z
dc.date.available2020-09-02T22:16:49Z
dc.date.issued2019
dc.identifier10.1002/glia.23631
dc.identifier.citation67, 8, 1598-1619
dc.identifier.issn08941491
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4345
dc.descriptionDiverse studies have suggested that cytoplasmic inclusions of misfolded α-synuclein in neuronal and glial cells are main pathological features of different α-synucleinopathies, including Parkinson's disease and dementia with Lewy bodies. Up to now, most studies have focused on the effects of α-synuclein on neurons, whereas the possible alterations of astrocyte functions and neuron–glia crosstalk have received minor attention. Recent evidence indicates that cellular signaling mediated by hemichannels and pannexons is critical for astroglial function and dysfunction. These channels constitute a diffusional route of communication between the cytosol and the extracellular space and during pathological scenarios they may lead to homeostatic disturbances linked to the pathogenesis and progression of different diseases. Here, we found that α-synuclein enhances the opening of connexin 43 (Cx43) hemichannels and pannexin-1 (Panx1) channels in mouse cortical astrocytes. This response was linked to the activation of cytokines, the p38 MAP kinase, the inducible nitric oxide synthase, cyclooxygenase 2, intracellular free Ca2+ concentration ([Ca2+]i), and purinergic and glutamatergic signaling. Relevantly, the α-synuclein-induced opening of hemichannels and pannexons resulted in alterations in [Ca2+]i dynamics, nitric oxide (NO) production, gliotransmitter release, mitochondrial morphology, and astrocyte survival. We propose that α-synuclein-mediated opening of astroglial Cx43 hemichannels and Panx1 channels might constitute a novel mechanism involved in the pathogenesis and progression of α-synucleinopathies. © 2019 Wiley Periodicals, Inc.
dc.language.isoen
dc.publisherJohn Wiley and Sons Inc.
dc.subjectconnexin
dc.subjectglia
dc.subjectneuroinflammation
dc.subjectpannexin
dc.subjectα-synucleinopathies
dc.subjectalpha synuclein
dc.subjectbrain protein
dc.subjectconnexin 43
dc.subjectcyclooxygenase 2
dc.subjectethidium
dc.subjectglutamic acid
dc.subjectinducible nitric oxide synthase
dc.subjectmitogen activated protein kinase p38
dc.subjectnitric oxide
dc.subjectpannexin 1
dc.subjectunclassified drug
dc.subjectagents interacting with transmitter, hormone or drug receptors
dc.subjectalpha synuclein
dc.subjectcalcium channel
dc.subjectconnexin 43
dc.subjectcytokine
dc.subjectgap junction protein
dc.subjectGJA1 protein, mouse
dc.subjectnerve protein
dc.subjectnitric oxide
dc.subjectPanx1 protein, mouse
dc.subjectsmall interfering RNA
dc.subjectSnca protein, mouse
dc.subjectanimal experiment
dc.subjectArticle
dc.subjectastrocyte
dc.subjectbrain cortex
dc.subjectcalcium cell level
dc.subjectcell death
dc.subjectcell survival
dc.subjectcontrolled study
dc.subjectglutamatergic synapse
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectanimal
dc.subjectastrocyte
dc.subjectbiosynthesis
dc.subjectcell communication
dc.subjectcell culture
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectmitochondrion
dc.subjectmouse
dc.subjectpathology
dc.subjectultrastructure
dc.subjectalpha-Synuclein
dc.subjectAnimals
dc.subjectAstrocytes
dc.subjectCalcium Channels
dc.subjectCell Communication
dc.subjectCell Death
dc.subjectCells, Cultured
dc.subjectConnexin 43
dc.subjectConnexins
dc.subjectCytokines
dc.subjectMice
dc.subjectMitochondria
dc.subjectNerve Tissue Proteins
dc.subjectNeurotransmitter Agents
dc.subjectNitric Oxide
dc.subjectRNA, Small Interfering
dc.titleConnexin 43 hemichannels and pannexin-1 channels contribute to the α-synuclein-induced dysfunction and death of astrocytes
dc.typeArticle


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