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

Simple item page
dc.contributor.authorDuarte, Yorley
dc.contributor.authorQuintana, Daisy
dc.contributor.authorMoraga-Amaro, Rodrigo
dc.contributor.authorDinamarca, Ivanka
dc.contributor.authorLemunao, Yordan
dc.contributor.authorCárdenas, Kevin
dc.contributor.authorBahamonde, Tamara
dc.contributor.authorBarrientos, Tabita
dc.contributor.authorOlivares, Pedro
dc.contributor.authorNavas, Camila
dc.contributor.authorCarvajal, Francisco J.
dc.contributor.authorSantibáñez, Yessenia
dc.contributor.authorCastro, Raimundo
dc.contributor.authorMeza, María Paz
dc.contributor.authorJorquera, Ramón
dc.contributor.authorGómez, Gonzalo I.
dc.contributor.authorHenke, Marina
dc.contributor.authorAlarcón, Rodrigo
dc.contributor.authorGabriel, Laureen A.
dc.contributor.authorSchiffmann, Susanne
dc.contributor.authorCerpa, Waldo
dc.contributor.authorRetamal, Mauricio A.
dc.contributor.authorSimon, Felipe
dc.contributor.authorLinsambarth, Sergio
dc.contributor.authorGonzález Nilo, Fernando
dc.contributor.authorStehberg, Jimmy
dc.date.accessioned2024-12-31T15:36:09Z
dc.date.available2024-12-31T15:36:09Z
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.description.versionVersión enviada
dc.format.extent68 p.
dc.identifier.citationY. Duarte, D. Quintana-Donoso, R. Moraga-Amaro, I. Dinamarca, Y. Lemunao, K. Cárdenas, T. Bahamonde, T. Barrientos, P. Olivares, C. Navas, F.J. Carvajal, Y. Santibánez, R. Castro-Lazo, M. Paz Meza, R. Jorquera, G.I. Gómez, M. Henke, R. Alarcón, L.A. Gabriel, S. Schiffmann, W. Cerpa, M.A. Retamal, F. Simon, S. Linsambarth, F. Gonzalez-Nilo, J. Stehberg, The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release, Proc. Natl. Acad. Sci. U.S.A. 121 (46) e2307953121, https://doi.org/10.1073/pnas.2307953121
dc.identifier.doihttps://doi.org/10.1073/pnas.2307953121
dc.identifier.urihttps://hdl.handle.net/11447/9547
dc.language.isoen
dc.subjectDepression
dc.subjectCx43 hemichannels
dc.subjectTAT-Cx43L2
dc.subjectCacotheline
dc.subject57 gliotransmission
dc.subjectAstrocytes
dc.titleThe role of astrocytes in depression, its prevention and treatment by targeting astroglial gliotransmitter release
dc.typeArticle
dcterms.accessRightsAcceso abierto
dcterms.sourceThe Proceedings of the National Academy of Sciences (PNAS)
dspace.entity.typePublication
relation.isAuthorOfPublication01e4a6fa-e55f-47c5-a1b6-383d5fc6f474
relation.isAuthorOfPublication.latestForDiscovery01e4a6fa-e55f-47c5-a1b6-383d5fc6f474

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
2024 PNAS Duarte et al_Proofs.pdf
Size:
3.37 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
347 B
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services