Narcolepsy in orexin Knockout Mice Molecular Genetics of Sleep Regulation

@article{Chemelli1999NarcolepsyIO,
  title={Narcolepsy in orexin Knockout Mice Molecular Genetics of Sleep Regulation},
  author={Richard M. Chemelli and Jon T. Willie and Christopher M. Sinton and Joel K Elmquist and Thomas E. Scammell and Charlotte E. Lee and James A. Richardson and S. C. R. Williams and Yumei Xiong and Yaz Y. Kisanuki and Thomas E. Fitch and Masamitsu Nakazato and Robert E. Hammer and Clifford B. Saper and Masashi Yanagisawa},
  journal={Cell},
  year={1999},
  volume={98},
  pages={437-451}
}
View on Elsevier
cell.com
2,821 Citations
Highly Influential Citations
137
Background Citations
1,020
Methods Citations
103
Results Citations
62

Figures and Tables from this paper

2,821 Citations

Citation Type

Citation Type

Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity
Dissecting Brain Circuitry for Sleep Disorder Narcolepsy in Murine Models
Orexin deficiency and narcolepsy
  • T. Sakurai
  • Psychology, Biology
    Current Opinion in Neurobiology
  • 2013
Orexin (Hypocretin) and Narcolepsy
TLDR
The current understanding of how the orexinergic system regulates sleep and wakefulness and how its deficiency causes narcolepsy is reviewed.
The roles of orexins in sleep/wake regulation
Hypocretin/Orexin: a molecular link between sleep, energy regulation, and pleasure.
  • H. Ganjavi, C. Shapiro
  • Biology, Psychology
    The Journal of neuropsychiatry and clinical neurosciences
  • 2007
TLDR
It is suggested that eating habits and impulsivity may be topics worth exploring in the evaluation of narcoleptic patients and the recent literature with regard to the many functions of Hcrt.
Ectopic Overexpression of Orexin Alters Sleep/Wakefulness States and Muscle Tone Regulation during REM Sleep in Mice
TLDR
Sleep/wakefulness abnormalities in transgenic mice that exhibit widespread overexpression of a rat prepro-orexin transgene driven by a β-actin/cytomegalovirus hybrid promoter are reported, suggesting that endogenous orexinergic activity should be appropriately regulated for normal maintenance of sleep states.
Title Orexin deficiency and narcolepsy
TLDR
The deficiency of orexin signaling in narcolepsy-cataplexy unequivocally shows that this neuropeptide system plays a physiologically essential role in the regulation of sleep and wakefulness, especially in the maintenance of long, consolidated waking periods.
Rodent Models of Human Narcolepsy-cataplexy
Behavioral and electrophysiological analysis of orexin -/- mice, together with studies on narcoleptic OX2R-deficient dogs, made a big jump in our understanding on narcolepsy-cataplexy, as well as…
Orexin neurons suppress narcolepsy via 2 distinct efferent pathways.
TLDR
It is suggested that DR serotonergic and LC noradrenergic neurons play differential roles in orexin neuron-dependent regulation of sleep/wakefulness and highlight a pharmacogenetic approach for the amelioration of narcolepsy.
...
...

References

SHOWING 1-10 OF 96 REFERENCES
The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene
PHARMACOLOGICAL ASPECTS OF HUMAN AND CANINE NARCOLEPSY
Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior
The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.
TLDR
A hypothalamus-specific mRNA is described that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin, suggesting that the hypocretins function within the CNS as neurotransmitters.
Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems
TLDR
The results of this immunohistochemical study suggest that hypocretins are likely to have a role in physiological functions in addition to food intake such as regulation of blood pressure, the neuroendocrine system, body temperature, and the sleep–waking cycle.
Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord
TLDR
Long descending axonal projections that contain hypocretin were found that innervate all levels of the spinal cord from cervical to sacral segments, as studied in mouse, rat, and human spinal cord and not previously described, suggesting that in addition to possible roles in feeding and endocrine regulation, the descending hypocrretin fiber system may play a role in modulation of sensory input.
Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems.
  • Y. Date, Y. Ueta, M. Nakazato
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
The unique neuronal distribution of orexins and their functional activation of neural circuits suggest specific complex roles of the peptides in autonomic and neuroendocrine control.
Muscle atonia is triggered by cholinergic stimulation of the basal forebrain: implication for the pathophysiology of canine narcolepsy
  • S. Nishino, M. Tafti, E. Mignot
  • Biology, Psychology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1995
TLDR
Results suggest that a cholinoceptive site in the BF is critically implicated in triggering muscle atonia and cataplexy, and it appears that a widespread hypersensitivity to cholinergic stimulation may be central to the pathophysiology of canine narcolepsy.
Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area
TLDR
Projections from populations of leptin‐responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight.
Investigations into the neurologic basis of narcolepsy
TLDR
Experimental findings suggest a hypersensitivity of the overall muscarinic cholinergic system and that this hypersensitive cholinergy system is linked to the limbic system, and suggest that an abnormal cholinerg-dopaminergic interaction could underlie the pathophysiology of narcolepsy.
...
...