PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus

Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (...

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Detalhes bibliográficos
Autores: Velasco, Erik R., Florido, Florido, Flores, África, Senabre Hidalgo, Enric, Gomez Gomez, Alex, Torres Martí, Antoni, Roca, Alba, Norrholm, Seth D, Newman, Emily L, Das, P, Ross, Rachel A., Lori, Adriana, Pozo, Oscar J., Ressler, Kerry J., García Esteve, Luisa, Jovanovic, Tanja, Andero, Raül
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/209449
Acesso em linha:https://hdl.handle.net/2445/209449
Access Level:Acceso aberto
Palavra-chave:Por
Trastorn per estrès posttraumàtic
Dones
Hipotàlem
Ratolins (Animals de laboratori)
Fear
Post-traumatic stress disorder
Women
Hypothalamus
Mice (Laboratory animals)
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oai_identifier_str oai:recercat.cat:2445/209449
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repository_id_str
spelling PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamusVelasco, Erik R.Florido, FloridoFlores, ÁfricaSenabre Hidalgo, EnricGomez Gomez, AlexTorres Martí, AntoniRoca, AlbaNorrholm, Seth DNewman, Emily LDas, PRoss, Rachel A.Lori, AdrianaPozo, Oscar J.Ressler, Kerry J.García Esteve, LuisaJovanovic, TanjaAndero, RaülPorTrastorn per estrès posttraumàticDonesHipotàlemRatolins (Animals de laboratori)FearPost-traumatic stress disorderWomenHypothalamusMice (Laboratory animals)Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/ΔFosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction.Nature Publishing Group2024202420222024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 p.application/pdfhttps://hdl.handle.net/2445/209449Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41467-022-31442-wNature Communications, 2022, vol. 13, num.1https://doi.org/10.1038/s41467-022-31442-wcc-by (c) Velasco, ER et al., 2022http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2094492026-05-29T05:05:01Z
dc.title.none.fl_str_mv PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
spellingShingle PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
Velasco, Erik R.
Por
Trastorn per estrès posttraumàtic
Dones
Hipotàlem
Ratolins (Animals de laboratori)
Fear
Post-traumatic stress disorder
Women
Hypothalamus
Mice (Laboratory animals)
title_short PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_full PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_fullStr PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_full_unstemmed PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_sort PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
dc.creator.none.fl_str_mv Velasco, Erik R.
Florido, Florido
Flores, África
Senabre Hidalgo, Enric
Gomez Gomez, Alex
Torres Martí, Antoni
Roca, Alba
Norrholm, Seth D
Newman, Emily L
Das, P
Ross, Rachel A.
Lori, Adriana
Pozo, Oscar J.
Ressler, Kerry J.
García Esteve, Luisa
Jovanovic, Tanja
Andero, Raül
author Velasco, Erik R.
author_facet Velasco, Erik R.
Florido, Florido
Flores, África
Senabre Hidalgo, Enric
Gomez Gomez, Alex
Torres Martí, Antoni
Roca, Alba
Norrholm, Seth D
Newman, Emily L
Das, P
Ross, Rachel A.
Lori, Adriana
Pozo, Oscar J.
Ressler, Kerry J.
García Esteve, Luisa
Jovanovic, Tanja
Andero, Raül
author_role author
author2 Florido, Florido
Flores, África
Senabre Hidalgo, Enric
Gomez Gomez, Alex
Torres Martí, Antoni
Roca, Alba
Norrholm, Seth D
Newman, Emily L
Das, P
Ross, Rachel A.
Lori, Adriana
Pozo, Oscar J.
Ressler, Kerry J.
García Esteve, Luisa
Jovanovic, Tanja
Andero, Raül
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Por
Trastorn per estrès posttraumàtic
Dones
Hipotàlem
Ratolins (Animals de laboratori)
Fear
Post-traumatic stress disorder
Women
Hypothalamus
Mice (Laboratory animals)
topic Por
Trastorn per estrès posttraumàtic
Dones
Hipotàlem
Ratolins (Animals de laboratori)
Fear
Post-traumatic stress disorder
Women
Hypothalamus
Mice (Laboratory animals)
description Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/ΔFosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction.
publishDate 2022
dc.date.none.fl_str_mv 2022
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/209449
url https://hdl.handle.net/2445/209449
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-31442-w
Nature Communications, 2022, vol. 13, num.1
https://doi.org/10.1038/s41467-022-31442-w
dc.rights.none.fl_str_mv cc-by (c) Velasco, ER et al., 2022
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Velasco, ER et al., 2022
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421896460664832
score 15,811543