{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:28:30Z","timestamp":1792171710864,"version":"4.4.0"},"reference-count":97,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220759\/Z\/20\/Z"],"award-info":[{"award-number":["220759\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["UK DRI-5004"],"award-info":[{"award-number":["UK DRI-5004"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,10,14]]},"abstract":"<jats:p>\n                    Activating the\n                    <jats:italic toggle=\"yes\">adra2a<\/jats:italic>\n                    receptors of the brain\u2019s norepinephrine (NE) system produces NREM-like sleep and hypothermia. Dexmedetomidine (DEX), a selective \u03b12 receptor (\n                    <jats:italic toggle=\"yes\">adra2a<\/jats:italic>\n                    ) agonist, is an important drug used in intensive care for arousable sedation. But for some patients, even slight decreases in body temperature during sedation could pose health risks such as increasing the likelihood of postoperative cognitive dysfunction. Where are the\n                    <jats:italic toggle=\"yes\">adra2a<\/jats:italic>\n                    receptors at which DEX acts to induce hypothermia? A popular theory is that inhibitory\n                    <jats:italic toggle=\"yes\">adra2a<\/jats:italic>\n                    receptors expressed on norepinephrinergic locus coeruleus (LC) neurons are DEX\u2019s prime targets. To examine this, we genetically lesioned\n                    <jats:italic toggle=\"yes\">galanin<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">gal<\/jats:italic>\n                    )-expressing norepinephrinergic LC neurons in adult mice. In these\n                    <jats:italic toggle=\"yes\">\u0394LC<\/jats:italic>\n                    mice, baseline sleep\u2013wake levels were unchanged, but surprisingly, core body temperatures were lower. Maintaining body temperature depended on NE\/\n                    <jats:italic toggle=\"yes\">gal<\/jats:italic>\n                    projections from the LC to the medial preoptic (MPO) hypothalamus. Furthermore, without these LC neurons, DEX induced hypothermia more strongly. Knockdown with\n                    <jats:italic toggle=\"yes\">adra2a shRNA<\/jats:italic>\n                    revealed that DEX induces hypothermia via\n                    <jats:italic toggle=\"yes\">adra2a<\/jats:italic>\n                    receptors on MPO glutamate cells. When\n                    <jats:italic toggle=\"yes\">\u0394LC<\/jats:italic>\n                    mice were kept warm, DEX could induce the same amount of NREM-like sleep as well as it did for mice with an intact LC, and this sleep-like state in\n                    <jats:italic toggle=\"yes\">\u0394LC<\/jats:italic>\n                    mice had a higher delta frequency power than in control mice. Our results emphasize that inhibition of the LC by DEX is not required to induce robust sedation. By contrast, the LC likely has a fortuitous background action in protecting against drug-induced hypothermia and speeds recovery from hypothermia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2422878122","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T15:54:42Z","timestamp":1759852482000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["The locus coeruleus maintains core body temperature and protects against hypothermia during dexmedetomidine-induced sedation"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7812-3754","authenticated-orcid":false,"given":"Berta","family":"Anuncibay Soto","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Imperial College London","place":["London, United Kingdom"]},{"name":"United Kingdom Dementia Research Institute at Imperial College London","place":["London, United 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