つくばリポジトリ SR 8 1 1285

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Hyper -hi ppocampal gl ycogen i nduced by gl ycogen l oadi ng wi t h exhaust i ve exer ci se 著者 j our nal or publ i cat i on t i t l e vol ume page r ange year 権利 URL Soya Mar i ko, Mat sui Takashi ,Shi ma Taker u, J esmi n Subr i na, Omi Naomi ,Soya Hi deaki Sci ent i f i c r epor t s 8 1285 2018- 01 (C) The Aut hor (s) 2018 Thi s ar t i cl e i s l i censed under a Cr eat i ve Commons At t r i but i on 4. 0 I nt er nat i onal Li cense, whi ch per mi t s use, shar i ng, adapt at i on, di st r i but i on and r epr oduct i on i n any medi um or f or mat ,as l ong as you gi ve appr opr i at e cr edi t t o t he or i gi nal aut hor (s) and t he sour ce, pr ovi de a l i nk t o t he Cr eat i ve Commons l i cense, and i ndi cat e i f changes wer e made. The i mages or ot her t hi r d par t y mat er i al i n t hi s ar t i cl e ar e i ncl uded i n t he ar t i cl e’ s Cr eat i ve Commons l i cense, unl ess i ndi cat ed ot her wi se i n a cr edi t l i ne t o t he mat er i al .I f mat er i al i s not i ncl uded i n t he ar t i cl e’ s Cr eat i ve Commons l i cense and your i nt ended use i s not per -mi t t ed by st at ut or y r egul at i on or exceeds t he per mi t t ed use, you wi l l need t o obt ai n per mi ssi on di r ect l y f r om t he copyr i ght hol der .To vi ew a copy of t hi s .ht t p: hdl .handl e. net /2241/ 00150982 doi: 10.1038/s41598-018-19445-4 Cr eat i ve Commons :表示 ht t p: cr eat i vecommons. or g/ l i censes/ by/ 3. 0/ deed. j a www.nature.com/scientificreports OPEN Received: 14 September 2017 Accepted: 28 December 2017 Published: xx xx xxxx Hyper-hippocampal glycogen induced by glycogen loading with exhaustive exercise Mariko Soya1, Takashi Matsui1,2, Takeru Shima1, Subrina Jesmin1, Naomi Omi3,4 &Hideaki Soya 1,2 Glycogen loading (GL),a well-known type of sports conditioning, in combination with exercise and a high carbohydrate diet (HCD) for 1 week enhances individual endurance capacity through muscle glycogen supercompensation. This exercise-diet combination is necessary for successful GL. Glycogen in the brain contributes to hippocampus-related memory functions and endurance capacity. Although the efect of HCD on the brain remains unknown, brain supercompensation occurs following exhaustive exercise (EE),a component of GL. We thus employed a rat model of GL and examined whether GL increases glycogen levels in the brain as well as in muscle, and found that GL increased glycogen levels in the hippocampus and hypothalamus, as well as in muscle. We further explored the essential components of GL (exercise and/or diet conditions) to establish a minimal model of GL focusing on the brain. Exercise, rather than a HCD, was found to be crucial for GL-induced hyper-glycogen in muscle, the hippocampus and the hypothalamus. Moreover, EE was essential for hyper-glycogen only in the hippocampus even without HCD. Here we propose the EE component of GL without HCD as a condition that enhances brain glycogen stores especially in the hippocampus, implicating a physiological strategy to enhance hippocampal functions. Glycogen is an important energy source for muscle during exercise, and it is depleted with increased intensity and/or duration of exercise1. Such glycogen depletion leads to muscle fatigue during endurance exercise2–4. To avoid muscle fatigue, muscle glycogen-loading (GL) a well-established sports conditioning strategy including both exercise and diet for 1 week before competition –increases muscle glycogen levels and enhances the endurance capacity in humans and animals5–8. GL has been developed using a popular theory called “muscle glycogen supercompensation”,which is characterized by an initial depletion of muscle glycogen levels followed by a considerable replenishment of muscle glycogen 24–48 hours ater acute exercise9–11. Åstrand irst proposed the classic GL protocol: 3 days of exercising and a low-carbohydrate diet to induce muscle glycogen depletion followed by 3 days of a high-carbohydrate diet for hyper muscle glycogen12. However, classic GL protocol is complicated and occasionally induces restlessness with hypoglycemia due to the 3 days of low carbohydrate diet5,13. To solve these problems, Sherman et al. established a novel GL protocol using only a high-carbohydrate diet and exercises that induced hyper muscle glycogen mirroring the classic protocol7. his novel GL protocol is popular among modern endurance athletes14,15. Interestingly, similar type of glycogen supercompensation phenomena in the brain were observed in our recent study16. We found that brain glycogen decreases with exhaustive exercise17, particularly in the hippocampus and cortex, and that supercompensation occurs, as it does in muscle, 6 hours ater exhaustive exercise in rats16. hese elevated glycogen levels were sustained for up to 24 hours ater exhaustive exercise16. herefore, we have hypothesized that GL increases brain glycogen storage, as observed in muscle, based on the exercise-induced glycogen-supercompensation theory as mentioned above. Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba -8 7 ,Ibaraki, Japan. Department of Sport Neuroscience, Advanced Research Initiative for Human High Performance (ARIHHP),Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 8 7 ,Ibaraki, Japan. Laboratory of Exercise Nutrition, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba -8 7 ,Ibaraki, Japan. Department of Body, ARIHHP, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba -8 7 ,Ibaraki, Japan. Correspondence and requests for materials should be addressed to T.M. email: matsui.takashi.ga@u.tsukuba.ac.jp) or H.S. email: soya.hideaki.gt@u.tsukuba.ac.jp) SCIENTIFIC REPORTS |2018) 8:1285 |DOI: 8/s 98- 8- 9 1 www.nature.com/scientificreports/ Brain glycogen, which is localized in astrocytes and produces lactate as a neuronal energy source and/or neuromodulator, plays a critical role in memory function and exercise endurance18–22. Chronic exercise that enhances endurance capacity and cognitive function has also been accompanied with elevated hippocampal glycogen levels in normal rats16. In our very recent study, 4 weeks of moderate exercise is efective in improving the declining memory function (hippocampal) in type 2 diabetic rats, and this exercise-induced hippocampal-memory amelioration has been associated with hyper-glycogen levels in the hippocampus23. Indeed, recent studies have demonstrated that pharmacological or genetic inhibition of hippocampal glycogen metabolism impairs memory formation and compromises endurance capacity19–22,24. Furthermore, pharmacologically elevated brain glycogen levels in the brain protect neuronal activities under insulin-induced severe hypoglycemia25. herefore, if GL increases brain glycogen levels as it does in muscle, GL is a possible strategy to enhance brain functions relating with memory and endurance performance. To study the efects of GL on brain, determination of an appropriate GL condition for animals is needed. To date, Shinohara’s 1 week GL model, which is composed of an exhaustive exercise followed by a moderate exercise (10 min with a weight equal to 1–2% of body mass) and then rest with HCD, is useful as a reference because in their model hyper-glycogen storage has appeared in rat muscle ater the GL8. However, their analysis is inadequate since the roles of the respective components of GL, namely EX (exhaustive exercise followed by moderate exercise and rest) and HCD, on glycogen storage is still unclear, and they did not address brain glycogen storage. We thus performed four experiments as follows: First, we employed GL protocols, EX with HCD, in rat models and assessed whether glycogen levels increased ater GL in various regions of the brains especially in the hippocampus, and in muscle (Experiment 1, Fig. 1A).Subsequently, we examined which GL component is dominant, EX or HCD, in inducing hyper-glycogen levels in the brain (HCD: Experiment 2, Fig. 1B; EX: Experiment 3, Fig. 1C, exercise conditions: Experiment 4, Fig. 1D).hrough these analyses we intended to clarify whether GL or one of its two main components (EX and HCD) may have positive efects on brain glycogen storage. Results GL increases glycogen levels in both muscle and brain. Rats underwent 1-week of GL, which consisted of several EX conditions and a HCD. Glycogen levels in muscle, liver and brain ater GL were measured by using microwave irradiation (Fig. 2A).Muscle glycogen, but not liver glycogen, increased ater GL (EX with HCD) P

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