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Increased plasma melatonin in presymptomatic Huntington disease sheep ( Ovis aries ): Compensatory neuroprotection in a neurodegenerative disease?

Morton, A. Jennifer, Middleton, Benita, Rudiger, Skye, Bawden, C. Simon, Kuchel, Timothy R. and Skene, Debra (2020) Increased plasma melatonin in presymptomatic Huntington disease sheep ( Ovis aries ): Compensatory neuroprotection in a neurodegenerative disease? Journal of Pineal Research, 68 (2), e12624.

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Melatonin is a pleiotrophic hormone, synthesised primarily by the pineal gland under the control of the suprachiasmatic nuclei (SCN). It not only provides a hormonal signal of darkness but also has neuroprotective properties. Huntington's disease (HD) is a progressive neurodegenerative disorder characterised by abnormal motor, cognitive and psychiatric symptoms. There is growing evidence, particularly from animal models, that circadian rhythms may also be disturbed in HD. We measured two circadian‐regulated hormones, melatonin and cortisol, in plasma samples collected around‐the‐clock from normal and presymptomatic transgenic HD sheep (Ovis aries) at 5 and 7 years of age, to assess SCN‐driven rhythms and the effect of genotype, sex and age. Melatonin‐related precursors and metabolites (tryptophan, serotonin, kynurenine) were also measured by liquid chromatography (LC)‐mass spectrometry (MS). At 5 years of age in both rams and ewes, plasma melatonin levels were significantly elevated in HD sheep. In ewes measured 2 years later, there was still a significant elevation of nocturnal melatonin. Furthermore, the daytime baseline levels of melatonin were significantly higher in HD sheep. Since increased melatonin could have global beneficial effects on brain function, we suggest that the increased melatonin measured in presymptomatic HD sheep is part of an autoprotective response to mutant huntingtin toxicity that may account, at least in part, for the late onset of disease that characterises HD.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Morton, A. Jennifer
Rudiger, Skye
Bawden, C. Simon
Kuchel, Timothy R.
Date : 6 February 2020
Funders : Biotechnology and Biological Sciences Research Council (BBSRC)
DOI : 10.1111/jpi.12624
Copyright Disclaimer : © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Uncontrolled Keywords : Cognitive function; Huntington's disease; Kynurenine; Melatonin biosynthesis; Metabolomics; Neurodegenerative disease; Serotonin; Tryptophan metabolites
Depositing User : James Marshall
Date Deposited : 24 Jan 2020 11:49
Last Modified : 27 Apr 2020 15:11

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