2016 Fiscal Year Research-status Report
Elucidation of the molecular mechanisms of zinc-induced sleep
| Project/Area Number |
16K18698
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| Research Institution | University of Tsukuba |
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Principal Investigator |
シェラス ヨアン 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60544319)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | zinc / sleep / molecular mechanisms |
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| Outline of Annual Research Achievements |
Zinc is an essential mineral that plays an important role in the body. We previously reported that orally feeding zinc-enriched yeast to mice induces non-rapid-eye-movement sleep. In addition, astaxanthin, an antioxidant abundant in seafood such as salmon and krill, is able to chelate minerals and may promote zinc absorption, which in return may also improve sleep. The purpose of our study was to examine the effect of zinc-rich and astaxanthin-containing food on sleep in humans.
Methods and results: We conducted a randomized, double-blinded, placebo-controlled parallel group trial of 120 healthy subjects and recorded their night activity by actigraphy for 12 weeks. These subjects were divided into 4 groups: placebo, zinc-rich food, zinc- and astaxanthin-rich food, and placebo supplemented with zinc-enriched yeast and astaxanthin oil. Compared with the placebo group, the zinc-rich food group efficiently decreased the time necessary to fall asleep and improved sleep efficiency, whereas the group that ingested zinc-enriched yeast and astaxanthin oil significantly improved the sleep onset latency.
Conclusion: Actigraphic sleep monitoring demonstrated that eating zinc-rich food improved sleep onset latency as well as improved the sleep efficiency in healthy individuals.
Our results have been published in Saito, Cherasse et al., Mol Nutr Food Res., 2016 (DOI: 10.1002/mnfr.201600882).
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We designed a zinc-deficient diet, which allows us to manipulate zinc concentration in the blood of mice without affecting the body weight or global health of the animal. By using this diet, we evaluated the effect of a zinc deprivation on sleep in mice. Our data shows that mice subjected to zinc deprivation becomes more sensitive to yeast zinc administration (100mg/kg), with an increase of NREM sleep from 166.2mn (control mice) to 238.6mn (zinc deprived mice) during the 6 hours following administration.
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| Strategy for Future Research Activity |
We will determine the molecular mechanisms involved in the regulation of sleep by zinc. To do so, we will identify which brain regions are specifically activated by zinc. We will time-dependently check the expression of c-fos after zinc administration to determine the sequential activation of the different brain regions identified. Then we will confirm the involvement of the identified regions by stereotaxically injecting AAV-DTA (AAV driving the expression of the neurotoxin DTA, inducing neuronal death). We will also use AAVs expressing mutant G protein coupled receptors that respond to otherwise inert compounds to activate (hM3Dq) or inactivate (hM4Di) G protein signaling of neurons into the zinc controlled brain regions. Finally, after identifying the brain regions involved in zinc-induced sleep regulation we will perform double immunostaining to identify and characterize the neurons and neurotransmitters involved in such mechanisms.
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| Causes of Carryover |
A certain amount of financing previously expected to be used for travel fee in FY2016 remained unused (conferences were held in Kanto area and did not require hotel or expensive travel fee.
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| Expenditure Plan for Carryover Budget |
A certain amount of financing previously expected to be used for travel fee in FY2016 will be transferred to cover travel fee of FY2017 in international conference (WolrdSleep 2017, October 6-11, 2017; Prague, Czech Republic).
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Research Products
(3 results)
