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The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), the main driver of HPA axis regulation, and\n                    <jats:italic>FKBP5<\/jats:italic>\n                    polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. We here demonstrate that the deletion of\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    in Sim1\n                    <jats:sup>+<\/jats:sup>\n                    neurons dampens the acute stress response and increases GR sensitivity. In contrast,\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    overexpression in the PVN results in a chronic HPA axis over-activation, and a PVN-specific rescue of\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    expression in full\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    KO mice normalizes the HPA axis phenotype. Single-cell RNA sequencing revealed the cell-type-specific expression pattern of\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    in the PVN and showed that\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    expression is specifically upregulated in\n                    <jats:italic>Crh<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    neurons after stress. Finally,\n                    <jats:italic>Crh<\/jats:italic>\n                    -specific\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    overexpression alters\n                    <jats:italic>Crh<\/jats:italic>\n                    neuron activity, but only partially recapitulates the PVN-specific\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    overexpression phenotype. Together, the data establish the central and cell-type-specific importance of\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    in the PVN in shaping HPA axis regulation and the acute stress response.\n                  <\/jats:p>","DOI":"10.1038\/s41380-021-01044-x","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T04:03:19Z","timestamp":1614571399000},"page":"3060-3076","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus of male mice"],"prefix":"10.1038","volume":"26","author":[{"given":"Alexander S.","family":"H\u00e4usl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea M.","family":"Brix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1960-8177","authenticated-orcid":false,"given":"Jakob","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max L.","family":"P\u00f6hlmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Pablo","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danusa","family":"Menegaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6213-0973","authenticated-orcid":false,"given":"Elena","family":"Brivio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Engelhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Roeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bajaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Rudolph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Stoffel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Hafner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Goss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-4012","authenticated-orcid":false,"given":"Johannes M. 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