Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice

Bibliographic Details
Main Author: Queiroga, Cláudia S F
Publication Date: 2016
Other Authors: Alves, Raquel M A, V Conde, Silvia, Alves, Paula M, Vieira, Helena L A
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/21942
Summary: © 2016. Published by The Company of Biologists Ltd.
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spelling Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in miceApoptosisBrainCarbon monoxideCo-culturesPurinergicPreconditioning© 2016. Published by The Company of Biologists Ltd.The neuroprotective role of carbon monoxide (CO) has been studied in a cell-autonomous mode. Herein, a new concept is disclosed - CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A2A-R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A2A-R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNQueiroga, Cláudia S FAlves, Raquel M AV Conde, SilviaAlves, Paula MVieira, Helena L A2017-07-13T22:01:16Z2016-08-152016-08-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://hdl.handle.net/10362/21942eng0021-9533PURE: 1755286https://doi.org/10.1242/jcs.187260info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-05-26T01:38:41Zoai:run.unl.pt:10362/21942Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T16:57:48.231908Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
title Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
spellingShingle Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
Queiroga, Cláudia S F
Apoptosis
Brain
Carbon monoxide
Co-cultures
Purinergic
Preconditioning
title_short Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
title_full Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
title_fullStr Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
title_full_unstemmed Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
title_sort Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice
author Queiroga, Cláudia S F
author_facet Queiroga, Cláudia S F
Alves, Raquel M A
V Conde, Silvia
Alves, Paula M
Vieira, Helena L A
author_role author
author2 Alves, Raquel M A
V Conde, Silvia
Alves, Paula M
Vieira, Helena L A
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Queiroga, Cláudia S F
Alves, Raquel M A
V Conde, Silvia
Alves, Paula M
Vieira, Helena L A
dc.subject.por.fl_str_mv Apoptosis
Brain
Carbon monoxide
Co-cultures
Purinergic
Preconditioning
topic Apoptosis
Brain
Carbon monoxide
Co-cultures
Purinergic
Preconditioning
description © 2016. Published by The Company of Biologists Ltd.
publishDate 2016
dc.date.none.fl_str_mv 2016-08-15
2016-08-15T00:00:00Z
2017-07-13T22:01:16Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/21942
url http://hdl.handle.net/10362/21942
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0021-9533
PURE: 1755286
https://doi.org/10.1242/jcs.187260
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11
application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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