Background: Cataplexy is a loss of muscle tone that can lead to postural collapse, disturbing the daily life of narcolepsy patients; it is often triggered by positive emotions such as laughter in human patients. Narcolepsy model mice also show cataplexy, and its incidence increases in response to positive emotion-inducing stimuli such as chocolate and female courtship. Although such observation indicates a positive emotion-related nature of cataplexy in narcolepsy mice, they also show cataplexy without any apparent triggering stimulus ~ (spontaneous cataplexy). Therefore, we hypothesized that some spontaneous cataplexy in narcoleptic mice might indicate the remembering of happy moments.
Results: To test our hypothesis, we did a conditioned place preference test on orexin/hypocretin neuron-ablated (ORX-AB) mice, one of the animal models of human narcolepsy, and counted the number of cataplexy-like behaviors. ORX-AB mice successfully remembered the chocolate-associated chamber, and the number of cataplexy-like behaviors significantly increased in the chocolate-associated chamber but not in the control chamber. In addition, ORX-AB mice remembered the aversive odor-associated chamber and avoided entering without affecting the number of cataplexy-like behaviors. Finally, similar activation of the nucleus accumbens, a positive emotion-related nucleus, was observed during both spontaneous and chocolate-induced cataplexy behaviors.
Conclusions: These results support our hypothesis and will promote the usefulness of a narcolepsy mice model in emotion research and serve as a basis for a better understanding of cataplexy in narcolepsy patients.
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http://dx.doi.org/10.1186/s12868-022-00772-2 | DOI Listing |
J Sleep Res
July 2024
Laboratory of Physiological Regulation in Sleeping Mice (PRISM), Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
Narcolepsy type-1 (NT1) is a lifelong sleep disease, characterised by impairment of the orexinergic system, with a typical onset during adolescence and young adulthood. Since the wake-sleep cycle physiologically changes with ageing, this study aims to compare sleep patterns between orexin-knockout (KO) and wild type (WT) control mice at different ages. Four groups of age-matched female KO and WT mice (16 weeks of age: 8 KO-YO and 9 WT-YO mice; 87 weeks of age: 13 KO-OLD and 12 WT-OLD mice) were implanted with electrodes for discriminating wakefulness, rapid-eye-movement sleep (REMS), and non-REMS (NREMS).
View Article and Find Full Text PDFPeptides
July 2023
Chinese Institute for Brain Research, Beijing (CIBR), Beijing 102206, China; National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi 444-8585, Japan; Division of Brain Sciences Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address:
Orexin (also known as hypocretin) is a neuropeptide exclusively synthesized in the neurons of the lateral hypothalamus (LH). Initially orexin was thought to be involved in the regulation of feeding behavior. However, it is now known to also be a critical regulator of sleep/wakefulness, especially the maintenance of wakefulness.
View Article and Find Full Text PDFSci Rep
February 2023
Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Cataplexy is one of the symptoms of type 1 narcolepsy, characterized by a sudden loss of muscle tone. It can be seen as a behavioral index of salience, predominantly positive emotion, since it is triggered by laughter in humans and palatable foods in mice. In our previous study using chemogenetic techniques in narcoleptic mice (orexin neuron-ablated mice), we found that the rostral nucleus accumbens (NAc) shell is needed for chocolate-induced cataplexy.
View Article and Find Full Text PDFBMC Neurosci
December 2022
Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, 890-8544, Japan.
Background: Cataplexy is a loss of muscle tone that can lead to postural collapse, disturbing the daily life of narcolepsy patients; it is often triggered by positive emotions such as laughter in human patients. Narcolepsy model mice also show cataplexy, and its incidence increases in response to positive emotion-inducing stimuli such as chocolate and female courtship. Although such observation indicates a positive emotion-related nature of cataplexy in narcolepsy mice, they also show cataplexy without any apparent triggering stimulus ~ (spontaneous cataplexy).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2022
Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University Medical School, Palo Alto, CA 94304.
Narcolepsy type 1 (NT1) is a sleep disorder caused by a loss of orexinergic neurons. Narcolepsy type 2 (NT2) is heterogeneous; affected individuals typically have normal orexin levels. Following evaluation in mice, the effects of the orexin 2 receptor (OX2R)-selective agonist danavorexton were evaluated in single- and multiple-rising-dose studies in healthy adults, and in individuals with NT1 and NT2.
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