Orexin neurons are indispensable for stress-induced thermogenesis in mice W. Zhang and others Orexin neurons in stress-induced hyperthermia.

Orexin neurons contribute to cardiovascular, respiratory and analgesic components of the fight-or-flight response against stressors. Here, we examined whether the same is true for stress-induced hyperthermia. We used prepro-orexin knockout mice (ORX-KO) and orexin neuron-ablated mice (ORX-AB) in which the latter lack not only orexin, but also other putative neurotransmitter/modulators contained in the orexin neurons. In response to repetitive insertion of a temperature probe into their rectum (handling stress), ORX-KO mice showed a normal temperature change as compared to that of wild-type littermates (WT) while ORX-AB showed an attenuated response. Stress-induced expression of uncoupling protein-1, a key molecule in non-shivering thermogenesis in the brown adipose tissue (BAT), was also blunted in ORX-AB but not in ORX-KO. When the BAT was directly activated by a β3 adrenergic agonist, there was no difference in the resultant BAT temperature among the groups, indicating that BAT per se was normal in ORX-AB. In WT and ORX-KO, handling stress activated orexin neurons (as revealed by increased expression of c-Fos) and the resultant hyperthermia was largely blunted by pre-treatment with a β3 antagonist. This observation further supports the notion that attenuated stress-induced hyperthermia in ORX-AB mice was caused by a loss of orexin neurons and abnormal BAT regulation. This study pointed out, for the first time, the possible importance of co-existent neurotransmitter/modulators in the orexin neurons for stress-induced hyperthermia and the importance of integrity of the orexin neurons for full expression of multiple facets of the fight-or-flight response. Stress increases cardiac function, ventilation and body temperature. These changes prepare the body for fight-or-flight behaviour by increasing the metabolic rate, oxygen supply and by conduction velocity of nerve impulses. We previously demonstrated that cardiorespiratory excitation during stress depends on the level of the hypothalamic neuropeptide orexin. We examined whether the same is true for stress-induced hyperthermia. Orexin neuron-ablated mice (ORX-AB) showed attenuated stress-induced hyperthermia, but their basal body temperature was normal. The brown adipose tissue, which is a major thermogenic organ in rodents, did not respond to stress; however, it did respond to a direct pharmacological stimulation. These abnormalities in ORX-AB were not observed in orexin knockout mice, in which the orexin peptide is deficient but neurons are preserved. Therefore, the integrity (orexin and other co-existing neurotransmitters/modulators) of the orexin neurons is indispensable for full expression of the multiple factors involved in the fight-or-flight response. [ABSTRACT FROM AUTHOR]