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http://hdl.handle.net/2445/209449
Title: | PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus |
Author: | 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 |
Keywords: | Por Trastorn per estrès posttraumàtic Dones Hipotàlem Ratolins (Animals de laboratori) Fear Post-traumatic stress disorder Women Hypothalamus Mice (Laboratory animals) |
Issue Date: | 28-Jul-2022 |
Publisher: | Nature Publishing Group |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-31442-w |
It is part of: | Nature Communications, 2022, vol. 13, num.1 |
URI: | http://hdl.handle.net/2445/209449 |
Related resource: | https://doi.org/10.1038/s41467-022-31442-w |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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