The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release

Simple item page
dc.article.numbere2307953121
dc.catalogadorjca
dc.contributor.authorDuarte, Y.
dc.contributor.authorQuintana-Donoso, D.
dc.contributor.authorMoraga-Amaro, R.
dc.contributor.authorDinamarca, I.
dc.contributor.authorLemunao, Y.
dc.contributor.authorCardenas, K.
dc.contributor.authorBahamonde, T.
dc.contributor.authorBarrientos, T.
dc.contributor.authorOlivares, P.
dc.contributor.authorNavas, C.
dc.contributor.authorCarvajal, F.J.
dc.contributor.authorSantibanez, Y.
dc.contributor.authorCastro-Lazo, R.
dc.contributor.authorPaz Meza, M.
dc.contributor.authorJorquera, R.
dc.contributor.authorGomez, G.I.
dc.contributor.authorHenke, M.
dc.contributor.authorAlarcon, R.
dc.contributor.authorGabriel, L.A.
dc.contributor.authorSchiffmann, S.
dc.contributor.authorCerpa Nebott, Waldo
dc.contributor.authorRetamal, M.A.
dc.contributor.authorSimon, F.
dc.contributor.authorLinsambarth, S.
dc.contributor.authorGonzalez-Nilo, F.
dc.contributor.authorStehberg, J.
dc.date.accessioned2025-03-12T19:27:29Z
dc.date.available2025-03-12T19:27:29Z
dc.date.issued2024
dc.description.abstractThe role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and glutamate buildup. Moreover, the acute blockade of Cx43 hemichannels induced antidepressant effects in rats previously subjected to CRS or CUMS. This antidepressant effect was prevented by coinjection of glutamate and D-serine. Furthermore, Cx43 hemichannel blockade decreased postsynaptic NMDAR currents in vHipp slices in a glutamate and D-serine-dependent manner. Notably, chronic microinfusion of glutamate and D-serine, L-serine, or the NMDAR agonist NMDA, into the vHipp induced depressive-like symptoms in nonstressed rats. We also identified a small molecule, cacotheline, which blocks Cx43 hemichannels and its systemic administration induced rapid antidepressant effects, preventing stress-induced increases in astroglial Cx43 hemichannel activity and extracellular glutamate in the vHipp, without sedative or locomotor side effects. In conclusion, chronic stress increases Cx43 hemichannel-dependent release of glutamate and D-/L-serine from astrocytes in the vHipp, overactivating postsynaptic NMDARs and triggering depressive-like symptoms. This study highlights the critical role of astroglial gliotransmitter release in chronic stress-induced depression and suggests it can be used as a target for the prevention and treatment of depression.
dc.fechaingreso.objetodigital2025-03-12
dc.format.extent12 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1073/pnas.2307953121
dc.identifier.issn1091-6490
dc.identifier.scopusidSCOPUS_ID:85208516739
dc.identifier.urihttps://doi.org/10.1073/pnas.2307953121
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/102543
dc.information.autorucFacultad de Ciencias Biológicas; Cerpa Nebott, Waldo Francisco; 0000-0001-7344-0144; 16584
dc.issue.numero46
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaProceedings of the National Academy of Sciences of the United States of America
dc.rightsacceso abierto
dc.rights.licenseAttribution- NonCommercial-NoDerivatives License 4.0 (CC BY- NC- ND)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAstrocytes
dc.subjectCacotheline
dc.subjectCx43 hemichannels
dc.subjectDepression
dc.subjectTAT-Cx43L2
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release
dc.typeartículo
dc.volumen121
sipa.codpersvinculados16584
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
duarte-et-al-2024-the-role-of-astrocytes-in-depression-its-prevention-and-treatment-by-targeting-astroglial.pdf
Size:
3.38 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas