Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy

Autor: Ayumu Inutsuka, Ming Fung Wu, Ling Shan, Joshi John, Jerome M. Siegel, Rolf Fronczek, Gert Jan Lammers, Thomas C. Thannickal, Paul F. Worley, Keng Tee Chew, Dick F. Swaab, Lalini Ramanathan, Ronald McGregor, Marcia E. Cornford, Akihiro Yamanaka
Přispěvatelé: Netherlands Institute for Neuroscience (NIN), Academic Medical Center
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Cataplexy
Cell Count
Inbred C57BL
Medical and Health Sciences
Rats
Sprague-Dawley
Mice
Substance Misuse
0302 clinical medicine
2.1 Biological and endogenous factors
Aetiology
Neurons
education.field_of_study
Morphine
Neurogenesis
Brain
General Medicine
Biological Sciences
Neurological
medicine.symptom
Drug
psychological phenomena and processes
medicine.drug
Narcotics
Genetically modified mouse
medicine.medical_specialty
Substance-Related Disorders
Population
Article
Dose-Response Relationship
03 medical and health sciences
Internal medicine
mental disorders
medicine
Animals
Humans
education
Narcolepsy
Orexins
Dose-Response Relationship
Drug
business.industry
Animal
Opiate Alkaloids
Neurosciences
medicine.disease
Orexin
Rats
Brain Disorders
Mice
Inbred C57BL
Heroin
Disease Models
Animal
030104 developmental biology
Endocrinology
Good Health and Well Being
nervous system
Disease Models
Sprague-Dawley
business
Drug Abuse (NIDA only)
030217 neurology & neurosurgery
Hormone
Zdroj: Science translational medicine, vol 10, iss 447
Science Translational Medicine
Sci Transl Med
Science Translational Medicine, 10:eaao4953. American Association for the Advancement of Science (AAAS)
Science Translational Medicine, 10(447)
Science translational medicine, 10(447):eaao4953. American Association for the Advancement of Science
ResearcherID
ISSN: 1946-6234
Popis: The changes in brain function that perpetuate opiate addiction are unclear. In our studies of human narcolepsy, a disease caused by loss of immunohistochemically detected hypocretin (orexin) neurons, we encountered a control brain (from an apparently neurologically normal individual) with 50% more hypocretin neurons than other control human brains that we had studied. We discovered that this individual was a heroin addict. Studying five postmortem brains from heroin addicts, we report that the brain tissue had, on average, 54% more immunohistochemically detected neurons producing hypocretin than did control brains from neurologically normal subjects. Similar increases in hypocretin-producing cells could be induced in wild-type mice by long-term (but not short-term) administration of morphine. The increased number of detected hypocretin neurons was not due to neurogenesis and outlasted morphine administration by several weeks. The number of neurons containing melanin-concentrating hormone, which are in the same hypothalamic region as hypocretin-producing cells, did not change in response to morphine administration. Morphine administration restored the population of detected hypocretin cells to normal numbers in transgenic mice in which these neurons had been partially depleted. Morphine administration also decreased cataplexy in mice made narcoleptic by the depletion of hypocretin neurons. These findings suggest that opiate agonists may have a role in the treatment of narcolepsy, a disorder caused by hypocretin neuron loss, and that increased numbers of hypocretin-producing cells may play a role in maintaining opiate addiction.
Databáze: OpenAIRE
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