Key points• We recently showed that orexin neurons in the hypothalamus are indispensable for stress-induced thermogenesis.• In this study we examined whether the orexin neurons are also important for other forms of thermogenic processes, including brain prostaglandin E 2 (PGE 2 ) injection that mimics inflammatory fever and environmental cold exposure.• As was the case with stress-induced thermogenesis, orexin neuron-ablated (ORX-AB) mice exhibited a blunted PGE 2 -induced fever and intolerance to cold (5 • C) exposure.• Injection of retrograde tracer into the medullary raphe nucleus, where sympathetic premotor neurons regulating thermogenesis by the brown adipose tissue are located, revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice.• These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis. AbstractWe recently showed using prepro-orexin knockout (ORX-KO) mice and orexin neuron-ablated (ORX-AB) mice that orexin neurons in the hypothalamus, but not orexin peptides per se, are indispensable for stress-induced thermogenesis. To examine whether orexin neurons are more generally involved in central thermoregulatory mechanisms, we applied other forms of thermogenic perturbations, including brain prostaglandin E 2 (PGE 2 ) injections which mimic inflammatory fever and environmental cold exposure, to ORX-KO mice, ORX-AB mice and their wild-type (WT) litter mates. ORX-AB mice, but not ORX-KO mice, exhibited a blunted PGE 2 -induced fever and intolerance to cold (5 • C) exposure, and these findings were similar to the results previously obtained with stress-induced thermogenesis. PGE 2 -induced shivering was also attenuated in ORX-AB mice. Both mutants responded similarly to environmental heating (39• C). In WT and ORX-KO mice, the administration of PGE 2 and cold exposure activated orexin neurons, as revealed by increased levels of expression of c-fos. Injection of retrograde tracer into the medullary raphe nucleus revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice. In addition, we found that glutamate receptor antagonists (D-(-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione) but not orexin receptor antagonists (SB334867 and OX2 29) successfully inhibited PGE 2 -induced fever in WT mice. These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis. In addition, these results indicate the possible involvement of glutamate in orexin neurons implicated in PGE 2 -induced fever.

Objective: Few cases of Takotsubo cardiomyopathy with apical hypertrophic cardiomyopathy (APH)-like morphological changes during the recovery process have been reported. Patient: A 56-year-old woman diagnosed with Takotsubo cardiomyopathy showed a morphology similar to that of APH during recovery. We examined this patient using 2D speckle-tracking echocardiography based on the method used for hypertrophic cardiomyopathy, which suggested that the circumferential strain (CS) of the middle wall indicated myocardial function of the left ventricle, and the CS of the inner wall was associated with left ventricular chamber function. Results:We measured the CS of the endocardial, middle, and epicardial layers and found that the apical inner layer CS (CSinner), middle layer CS, and outer layer CS were all decreased at the onset. CSinner showed a strong tendency to recover on echocardiography performed when APH-like morphology was observed. Conclusion:The morphology of the apex in our case likely contributed to the maintenance of chamber function.

We have previously shown that handling stress‐induced thermogenesis depends on orexin‐containing neurons but not on orexin itself (J Physiol 588: 4117, 2010). In the present study, we examined whether the same is true or not with prostaglandin E2 (PGE2)‐induced fever and the defense against environmental cooling. We used prepro‐orexin knockout mice (ORX‐KO), orexin neuron‐ablated mice (ORX‐AB), and their controls. Increases in PGE2‐induced body temperature were significantly attenuated in ORX‐AB but not in ORX‐KO. PGE2‐induced shivering was also attenuated in ORX‐AB. In wild‐type mice, PGE2 induced fever was attenuated by pretreatment with glutamate receptor antagonists (AP5, CNQX) but not with orexin receptor antagonists (SB334867, OX2 29). ORX‐KO but not ORX‐AB tolerated a prolonged (>60 min, 5ºC) environmental cooling. Both mutants similarly responded to an environmental heating (39ºC). We conclude that orexin neurons play an important role in heat production during stress, fever, and cold exposure, while their contribution is minimal to an alleviation of body heat. Glutamate in orexin neurons probably mediates thermogenic responses.