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Abstract
Stress is one of major factors that cause sleep problems. Hypocretin represents a stress-related neuropeptide and is well known in maintaining physiological wakefulness. The hypocretinergic neurons originate in the lateral hypothalamic area (LHA) and transmit to several brain regions, including the median raphe nuclei (MRNs). The MRNs modulate both fear responses and sleep-wake activity; however, it remains unclear whether stress alters the levels of hypocretin to regulate MRNs and consequently disrupt sleep. In this paper, we employed the inescapable footshock stimuli (IFS) as a stressor and hypothesized that the IFS-induced sleep disruption is mediated by increased hypocretins in the MRNs. Our results demonstrate that the concentrations of hypocretin in the hypothalamus increased after IFS. Rapid eye movement (REM) sleep was reduced after footshock, and microinjection of non-selective hypocretin receptor antagonist TCS-1102 into the MRNs blocked the IFS-induced decrease of REM sleep. Furthermore, administration of hypocretins into the MRNs mimicked the IFS-induced REM sleep reduction. These results conclude that the increased levels of hypocretins in the MRNs mediate the IFS-induced REM sleep reduction.
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Details
1 National Taiwan University, Department of Veterinary Medicine, School of Veterinary Medicine, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241)
2 Leisure and Sports, Aletheia University, Department of Sport Management, College of Tourism, Taipei, Taiwan (GRID:grid.445069.a)
3 National Taiwan University, Department of Veterinary Medicine, School of Veterinary Medicine, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); National Taiwan University, Graduate Institute of Brain & Mind Sciences, College of Medicine, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241); China Medical University, Graduate Institute of Acupuncture Science, College of Chinese Medicine, Taichung, Taiwan (GRID:grid.254145.3) (ISNI:0000 0001 0083 6092)