{"doi":"10.1101/2022.12.21.521081","title":"Peripheral vs. Core Body Temperature as Hypocretin/Orexin Neurons Degenerate: Exercise Mitigates Increased Heat Loss","abstract":"Abstract Hypocretins/Orexins (Hcrt/Ox) are hypothalamic neuropeptides implicated in diverse functions, including body temperature regulation through modulation of sympathetic vasoconstrictor tone. In the current study, we measured subcutaneous (T sc ) and core (T b ) body temperature as well as activity in a conditional transgenic mouse strain that allows the inducible ablation of Hcrt/Ox-containing neurons by removal of doxycycline (DOX) from their diet ( orexin-DTA mice). Measurements were made during a baseline, when mice were being maintained on food containing DOX, and over 42 days while the mice were fed normal chow which resulted in Hcrt/Ox neuron degeneration. The home cages of the orexin-DTA mice were equipped with running wheels that were either locked or unlocked. In the presence of a locked running wheel, T sc progressively decreased on days 28 and 42 in the DOX(-) condition, primarily during the dark phase (the major active period for rodents). This nocturnal reduction in T sc was mitigated when mice had access to unlocked running wheels. In contrast to T sc , T b was largely maintained until day 42 in the DOX(-) condition even when the running wheel was locked. Acute changes in both T sc and T b were observed preceding, during, and following cataplexy. Our results suggest that ablation of Hcrt/Ox-containing neurons results in elevated heat loss, likely through reduced sympathetic vasoconstrictor tone, and that exercise may have some therapeutic benefit to patients with narcolepsy, a disorder caused by Hcrt/Ox deficiency. Acute changes in body temperature may facilitate prediction of cataplexy onset and lead to interventions to mitigate its occurrence. Highlights Hypocretin/Orexin (Hcrt/Ox) neuron degeneration results in the sleep disorder Narcolepsy and reduced subcutaneous body temperature (T sc ) during the dark phase of the 24-h light/dark cycle. This reduction in dark phase T sc is mitigated by access to an exercise opportunity. In contrast to T sc , core body temperature (T b ) is largely maintained as the Hcrt/Ox neurons degenerate. Reduced T sc while T b is maintained suggests increased heat loss, possibly through modulation of sympathetic vasoconstrictor tone. Hcrt/Ox neuron loss in Narcolepsy results in cataplexy, whose occurrence is associated with acute changes in both T sc and T b . Exercise may represent an effective intervention for mitigating heat loss resulting from Hcrt/Ox neuron loss in Narcolepsy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":305135,"datarank":0.11115713932150344,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.007185062237511627,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.007185062237511627,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":501509,"name":"Ryan K. Tisdale","orcid":"0000-0002-8239-6576","position":1,"is_corresponding":false},{"id":998628,"name":"Akira Yamashita","orcid":"0000-0002-6671-0430","position":2,"is_corresponding":false},{"id":392847,"name":"Thomas S. Kilduff","orcid":"0000-0002-6823-0094","position":3,"is_corresponding":false},{"id":766868,"name":"Yu Sun","orcid":"0000-0001-5002-1414","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:37.185846Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}