PRESERVED NUMBER OF OREXIN NEURONS IN POSTMORTEM HYPOTHALAMIC TISSUE OF CHRONIC ALCOHOLICS

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Abstract

The hypothalamic orexin system is critically involved in addiction, including chronic alcohol abuse. Microinjection of orexin into the lateral hypothalamus increases alcohol intake in rats, while reduced immunoreactivity of orexin neurons is associated with decreased alcohol drinking. Recently, the numbers of orexin neurons were found to be increased in opiate addiction in humans [4] and cocaine addiction in rats [2], but the integrity of orexin neurons has not yet been studied in human alcoholics. We examined the hypothalamus of 9 patients of chronic alcoholism and 10 subjects without a history of alcoholism or any other neurological or psychiatric disorder. We performed immunohistochemistry for orexin A, followed by stereological quantification. The hypothalamic tissue of chronic alcoholics exhibited a slightly increased number (9%) of orexin-containing neurons compared to the control group (123’087 ± 18’536 and 110’431 ± 14’439, p = 0.11). Mean Gundersen’s coefficient of error was 0.06 ± 0.01. The number of orexin neurons was similar in chronic alcoholics and control subjects without a history of alcoholism. Further examination of alcohol-induced hypothalamic damage is needed to understand, whether a neuroplastic increase in orexin neurons counterbalances a concurrent alcohol-toxic damage to these neurons.

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A S Kudriavova

Institute of Experimental Medicine, Saint Petersburg

V Meskenaite

University Hospital Zurich

V I Mikhailov

Alexandrovskaya City Hospital, Saint Petersburg

M Schesny

University Hospital Zurich

E A Korneva

Institute of Experimental Medicine, Saint Petersburg

Y V Gavrilov

Institute of Experimental Medicine, Saint Petersburg

P O Valko

University Hospital Zurich

References

  1. Harris GC, Aston-jones G. Arousal and reward: a dichotomy in orexin function. TRENDS in Neurosciences. 2006;10(29):571-577.
  2. James MH, et al. Increased Number and Activity of a Lateral Subpopulation of Hypothalamic Orexin/Hypocretin Neurons Underlies the Expression of an Addicted State in Rats. Biological Psychiatry. 2018.
  3. Schneider ER, et al. Orexigenic peptides and alcohol intake: Differential effects of orexin, galanin, and ghrelin. Alcoholism: Clinical and Experimental Research. 2007;11(31):1858-1865.
  4. Thannickal TC, et al. Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy. Science Translational Medicine. 2018;447(10):eaao4953.
  5. Valko PO, et al. Increase of histaminergic tuberomammillary neurons in narcolepsy. Annals of Neuro¬logy. 2013;(6)(74):794-804.

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Copyright (c) 2019 Kudriavova A.S., Meskenaite V., Mikhailov V.I., Schesny M., Korneva E.A., Gavrilov Y.V., Valko P.O.

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