The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fpsyt.2022.854494 http://hdl.handle.net/11449/240345 |
Resumo: | Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes. |
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The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomesdepressionmedium spiny neuronsnucleus accumbens (NAc)resiliencesocial defeat stresswitness defeatBrain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Anatomy and Neurobiology University of Maryland School of MedicineDepartment of Structural and Functional Biology University of CampinasSchool of Pharmaceutical Sciences São Paulo State UniversityDepartment of Psychology University of Texas at El PasoDepartment of Pharmacology University of São PauloDepartment of Anesthesiology Pennsylvania State College of MedicineSchool of Pharmaceutical Sciences São Paulo State UniversityFAPESP: 2018/05496-8University of Maryland School of MedicineUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (UNESP)University of Texas at El PasoUniversidade de São Paulo (USP)Pennsylvania State College of MedicinePagliusi, MarcoFranco, DanielaCole, ShannonMorais-Silva, Gessynger [UNESP]Chandra, RameshFox, Megan E.Iñiguez, Sergio D.Sartori, Cesar R.Lobo, Mary Kay2023-03-01T20:13:00Z2023-03-01T20:13:00Z2022-06-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fpsyt.2022.854494Frontiers in Psychiatry, v. 13.1664-0640http://hdl.handle.net/11449/24034510.3389/fpsyt.2022.8544942-s2.0-85132832871Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Psychiatryinfo:eu-repo/semantics/openAccess2023-03-01T20:13:00Zoai:repositorio.unesp.br:11449/240345Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-03-01T20:13Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes |
title |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes |
spellingShingle |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes Pagliusi, Marco depression medium spiny neurons nucleus accumbens (NAc) resilience social defeat stress witness defeat |
title_short |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes |
title_full |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes |
title_fullStr |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes |
title_full_unstemmed |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes |
title_sort |
The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes |
author |
Pagliusi, Marco |
author_facet |
Pagliusi, Marco Franco, Daniela Cole, Shannon Morais-Silva, Gessynger [UNESP] Chandra, Ramesh Fox, Megan E. Iñiguez, Sergio D. Sartori, Cesar R. Lobo, Mary Kay |
author_role |
author |
author2 |
Franco, Daniela Cole, Shannon Morais-Silva, Gessynger [UNESP] Chandra, Ramesh Fox, Megan E. Iñiguez, Sergio D. Sartori, Cesar R. Lobo, Mary Kay |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
University of Maryland School of Medicine Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (UNESP) University of Texas at El Paso Universidade de São Paulo (USP) Pennsylvania State College of Medicine |
dc.contributor.author.fl_str_mv |
Pagliusi, Marco Franco, Daniela Cole, Shannon Morais-Silva, Gessynger [UNESP] Chandra, Ramesh Fox, Megan E. Iñiguez, Sergio D. Sartori, Cesar R. Lobo, Mary Kay |
dc.subject.por.fl_str_mv |
depression medium spiny neurons nucleus accumbens (NAc) resilience social defeat stress witness defeat |
topic |
depression medium spiny neurons nucleus accumbens (NAc) resilience social defeat stress witness defeat |
description |
Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-06-02 2023-03-01T20:13:00Z 2023-03-01T20:13:00Z |
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://dx.doi.org/10.3389/fpsyt.2022.854494 Frontiers in Psychiatry, v. 13. 1664-0640 http://hdl.handle.net/11449/240345 10.3389/fpsyt.2022.854494 2-s2.0-85132832871 |
url |
http://dx.doi.org/10.3389/fpsyt.2022.854494 http://hdl.handle.net/11449/240345 |
identifier_str_mv |
Frontiers in Psychiatry, v. 13. 1664-0640 10.3389/fpsyt.2022.854494 2-s2.0-85132832871 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers in Psychiatry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1803649586124816384 |