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 (...
| Autores: | , , , , , , , , , , , , , , , , |
|---|---|
| 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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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) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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