Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression

dc.article.number39
dc.catalogadoryvc
dc.contributor.authorTichauer Calderón, Juan Enrique
dc.contributor.authorLira Mendieta, Matías Sebastián
dc.contributor.authorCerpa Nebott, Waldo Francisco
dc.contributor.authorOrellana Roca, Juan Andrés
dc.contributor.authorSáez Carreño, Juan Carlos
dc.contributor.authorRovegno Echavarría, David Maximiliano
dc.date.accessioned2024-06-25T15:32:20Z
dc.date.available2024-06-25T15:32:20Z
dc.date.issued2024
dc.date.updated2024-06-16T00:03:13Z
dc.description.abstractSpreading depression (SD) is an intriguing phenomenon characterized by massive slow brain depolarizations that affect neurons and glial cells. This phenomenon is repetitive and produces a metabolic overload that increases secondary damage. However, the mechanisms associated with the initiation and propagation of SD are unknown. Multiple lines of evidence indicate that persistent and uncontrolled opening of hemichannels could participate in the pathogenesis and progression of several neurological disorders including acute brain injuries. Here, we explored the contribution of astroglial hemichannels composed of connexin-43 (Cx43) or pannexin-1 (Panx1) to SD evoked by high-K+ stimulation in brain slices. Results Focal high-K+ stimulation rapidly evoked a wave of SD linked to increased activity of the Cx43 and Panx1 hemichannels in the brain cortex, as measured by light transmittance and dye uptake analysis, respectively. The activation of these channels occurs mainly in astrocytes but also in neurons. More importantly, the inhibition of both the Cx43 and Panx1 hemichannels completely prevented high K+-induced SD in the brain cortex. Electrophysiological recordings also revealed that Cx43 and Panx1 hemichannels critically contribute to the SD-induced decrease in synaptic transmission in the brain cortex and hippocampus. Conclusions Targeting Cx43 and Panx1 hemichannels could serve as a new therapeutic strategy to prevent the initiation and propagation of SD in several acute brain injuries.
dc.fechaingreso.objetodigital2024-06-16
dc.format.extent19 páginas
dc.fuente.origenBiomed Central
dc.identifier.citationBiological Research. 2024 Jun 12;57(1):39
dc.identifier.urihttps://doi.org/10.1186/s40659-024-00519-9
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86850
dc.information.autorucFacultad de Ciencias Biológicas;Tichauer Calderón, Juan Enrique; S/I;1492
dc.information.autorucFacultad de Ciencias Biológicas;Lira Mendieta, Matías Sebastián;S/I;1050702
dc.information.autorucFacultad de Ciencias Biológicas;Cerpa Nebott, Waldo Francisco; 0000-0001-7344-0144;16584
dc.information.autorucFacultad de Ciencias Biológicas;Orellana Roca, Juan Andrés; 0000-0003-4076-207X;126007
dc.information.autorucFacultad de Ciencias Biológicas;Sáez Carreño, Juan Carlos; 0000-0003-3811-0347;99913
dc.information.autorucEscuela de Medicina;Rovegno Echavarría, David Maximiliano; 0000-0002-2882-8024;1004053
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaBiological Research
dc.rightsacceso abierto
dc.rights.licenseCC BY Attribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSpreading depression
dc.subjectConnexin-43
dc.subjectPannexin-1
dc.subjectAstrocyte
dc.subjectNeurons
dc.subjectSynaptic transmission
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression
dc.typeartículo
dc.volumen57
sipa.codpersvinculados1492
sipa.codpersvinculados1050702
sipa.codpersvinculados16584
sipa.codpersvinculados126007
sipa.codpersvinculados99913
sipa.codpersvinculados1004053
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