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Melatonin modifies peripheral blood cell oscillators in humans
Author(s) -
Kostovski Emil,
Frigato Elena,
Dahm Anders,
Skretting Grethe,
Mowinkel MarieChristine,
Sandset Per Morten,
Iversen Per Ole,
Bertolucci Cristiano
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.614.3
Subject(s) - melatonin , clock , peripheral blood mononuclear cell , medicine , endocrinology , circadian rhythm , pineal gland , melatonin receptor , placebo , per1 , per2 , circadian clock , blood sampling , biology , genetics , alternative medicine , pathology , in vitro
Objective The blood concentrations of melatonin are highly associated with daylight patterns, with peak concentrations late at night. In healthy adults, the average daytime and peak night‐time values range from 10 to 200 pg/ml, however in tetraplegic persons the melatonin levels is blunted, ranging from 2 to15 pg/ml. Mounting evidence suggests that biological clocks, exist outside the central circadian pacemaker. We here explored how melatonin may influence oscillators in peripheral blood mononuclear cells (PBMCs) in tetraplegic and control persons. Study design and setting A double‐blind, randomized, placebo‐controlled cross‐over study, was conducted at Sunnaas Hospital, Nesoddtangen, Norway. Methods Six subjects with long‐standing complete tetraplegia received 2 mg of melatonin or placebo 4 days before sampling. We also included six able‐bodied men sleeping or being kept awake during the night. Plasma samples were collected from 4 to 10 times during 24‐hours. Expression of the period circadian clock‐1 (PER1) and −2 (PER2) genes, aryl hydrocarbon receptor nuclear translocator‐like protein 1 gene (BMAL1) and the nuclear receptor subfamily 1, group D, member 1 (REV‐ERB) gene was quantified in PBMCs using quantitative RT‐PCR (qRT‐PCR). The data were analysed using linear mixed models. Results Melatonin substitution increased night time melatonin plasma levels from 10 to 500 times in tetraplegic persons. The 24‐h profiles of all clock genes tended to differ (P < 0.09) or differed (P < 0.05) between tetraplegic patients receiving melatonin and tetraplegic patients receiving placebo, shifting and normalizing the mean maximum from a delayed peak (0400 h) in the tetraplegic patients receiving placebo towards the time of melatonin substitution (2200 h) in the tetraplegic persons receiving melatonin. There were no differences in the 24 h profile‐ or level‐expressions in able‐bodied staying awake compared to those sleeping or in between able‐bodied (all groups) compared to tetraplegic persons (all groups). Conclusions We here show differences in circadian variation of several clock genes related to melatonin concentration fluctuations in tetraplegic persons, suggesting that melatonin play a role in regulation of peripheral oscillators in humans. Support or Funding Information Sponsorship: Financial support was provided from the Throne Holst Foundation.