Peripheral vs. core body temperature as hypocretin/orexin neurons degenerate: Exercise mitigates increased heat loss

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.