|樋口 重和（ひぐち しげかず）||データ更新日：2020.06.15|
|1.||Sang‐il Lee,Kouhei Matsumori,Kana Nishimura,Yuki Nishimura,Yuki Ikeda,Taisuke Eto,Shigekazu Higuchi, Melatonin suppression and sleepiness in children exposed to blue‐enriched white LED lighting at night, Physiological Reports, 2018.12, [URL], Light‐induced melatonin suppression in children is reported to be more sensitive to white light at night than that in adults; however, it is unclear whether it depends on spectral distribution of lighting. In this study, we investigated the effects of different color temperatures of LED lighting on children's melatonin secretion during the night. Twenty‐two healthy children (8.9 ± 2.2 years old) and 20 adults (41.7 ± 4.4 years old) participated in this study. A between‐subjects design with four combinations, including two age groups (adults and children) and the two color temperature conditions (3000 K and 6200 K), was used. The experiment was conducted for two consecutive nights. On the first night, saliva samples were collected every hour under a dim light condition (<30 lx). On the second night, the participants were exposed to either color temperature condition. Melatonin suppression in children was greater than that in adults at both 3000 K and 6200 K condition. The 6200 K condition resulted in greater melatonin suppression than did the 3000 K condition in children (P < 0.05) but not in adults. Subjective sleepiness in children exposed to 6200 K light was significantly lower than that in children exposed to 3000 K light. In children, blue‐enriched LED lighting has a greater impact on melatonin suppression and it inhibits the increase in sleepiness during night. Light with a low color temperature is recommended at night, particularly for children's sleep and circadian rhythm..|
|2.||Shinobu Yasuo, Ayaka Iwamoto, Sang Il Lee, Shotaro Ochiai, Rina Hitachi, Satomi Shibata, Nobuo Uotsu, Chie Tarumizu, Sayuri Matsuoka, Mitsuhiro Furuse, Shigekazu Higuchi, L-serine enhances light-induced circadian phase resetting in mice and humans, Journal of Nutrition, 10.3945/jn.117.255380, 147, 12, 2347-2355, 2017.12, [URL], Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 L-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before L-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of L-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: L-Serine administration enhanced light-induced phase shifts inmice (1.86-fold; P < 0.05). Both L-serine and its metabolite D-serine, a coagonist of N-methyl-D-aspartic acid (NMDA) receptors, exerted this effect, but D-serine concentrations in the hypothalamus did not increase after L-serine administration. The effect of L-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. L-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, L-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, L-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-L-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05). Conclusion: These results suggest that L-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances..|
|3.||Tokiho Akiyama, Takafumi Katsumura, Shigeki Nakagome, Sang Il Lee, Keiichiro Joh, Hidenobu Soejima, Kazuma Fujimoto, Ryosuke Kimura, Hajime Ishida, Tsunehiko Hanihara, Akira Yasukouchi, Yoko Satta, Shigekazu Higuchi, Hiroki Oota, An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression, PLoS One, 10.1371/journal.pone.0178373, 12, 6, 2017.06, [URL], Humans show various responses to the environmental stimulus in individual levels as physiological variations. However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05). The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05), and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans..|
|4.||Kazuo Isoda, Kana Sueyoshi, Yuki Ikeda, Yuki Nishimura, Ichiro Hisanaga, Stéphanie Orlic, Yeon Kyu Kim, Shigekazu Higuchi, Effect of the hand-omitted tool motion on mu rhythm suppression, Frontiers in Human Neuroscience, 10.3389/fnhum.2016.00266, 10, 2016.06, [URL], In the present study, we investigated the effect of the image of hands on mu rhythm suppression invoked by the observation of a series of tool-based actions in a goal-directed activity. The participants were 11 university students. As a source of visual stimuli to be used in the test, a video animation of the porcelain making process for museums was used. In order to elucidate the effect of hand imagery, the image of hands was omitted from the original (“hand image included”) version of the animation to prepare another (“hand image omitted”) version. The present study has demonstrated that, an individual watching an instructive animation on the porcelain making process, the image of the porcelain maker’s hands can activate the mirror neuron system (MNS). In observations of “tool included” clips, even the “hand image omitted” clip induced significant mu rhythm suppression in the right central area. These results suggest that the visual observation of a tool-based action may be able to activate the MNS even in the absence of hand imagery..|
|5.||Shigekazu Higuchi, Sang Il Lee, Tomoaki Kozaki, Tetsuo Harada, Ikuo Tanaka, Late circadian phase in adults and children is correlated with use of high color temperature light at home at night, Chronobiology International, 10.3109/07420528.2016.1152978, 33, 4, 448-452, 2016.04, [URL], Light is the strongest synchronizer of human circadian rhythms, and exposure to residential light at night reportedly causes a delay of circadian rhythms. The present study was conducted to investigate the association between color temperature of light at home and circadian phase of salivary melatonin in adults and children. Twenty healthy children (mean age: 9.7 year) and 17 of their parents (mean age: 41.9 years) participated in the experiment. Circadian phase assessments were made with dim light melatonin onset (DLMO). There were large individual variations in DLMO both in adults and children. The average DLMO in adults and in children were 21:50 ± 1:12 and 20:55 ± 0:44, respectively. The average illuminance and color temperature of light at eye level were 139.6 ± 82.7 lx and 3862.0 ± 965.6 K, respectively. There were significant correlations between color temperature of light and DLMO in adults (r = 0.735, p < 0.01) and children (r = 0.479, p < 0.05), although no significant correlations were found between illuminance level and DLMO. The results suggest that high color temperature light at home might be a cause of the delay of circadian phase in adults and children..|
|6.||Shigekazu Higuchi, Yuki Nagafuchi, Sang Il Lee, Tetsuo Harada, Influence of light at night on melatonin suppression in children, Journal of Clinical Endocrinology and Metabolism, 10.1210/jc.2014-1629, 99, 9, 3298-3303, 2014.09, [URL], Context: The sensitivity of melatonin to light suppression is expected to be higher in children because children have large pupilsandpure crystal lenses. However, melatonin suppression by light in children remains unclear. Copyright
Objective: We investigated whether light-induced melatonin suppression in children is larger than that in adults.
Methods: Thirty-three healthy primary school children(meanage, 9.2±1.5 y)and29 healthy adults (meanage, 41.6±4.7 y) participated intwoexperiments. In the first experiment, salivary melatonin concentrations in 13 children and 13 adults were measured at night under a dim light (<30 lux) and a moderately bright light (580 lux) in an experimental facility. Pupil diameters were also measured under dim light and bright light. In the second experiment, melatonin concentrations in 20 children and 16 adults were measured under dim light in the experimental facility and under room light at home (illuminance, 140.0 ± 82.7 lux).
Results: In experiment 1, the melatonin concentration was significantly decreased by exposure to moderately bright light in both adults and children. Melatonin suppression was significantly larger in children (88.2%; n = 5) than in adults (46.3%; n = 6; P < .01), although the data for some participants were excluded because melatonin concentrations had not yet risen. In experiment 2, melatonin secretion was significantly suppressed by room light at home in children (n = 15; P < .05) but not in adults (n = 11).
Conclusion: We found that the percentage of melatonin suppression by light in children was almost twice that in adults, suggesting that melatonin is more sensitive to light in children than in adults at night..
|7.||樋口重和, 光の非視覚的作用と概日リズム：生理的多型性へのアプローチ, 日本生理人類学会誌, 18, 1, 39-43, 2013.03, [URL].|
|8.||Shigekazu Higuchi, Akiko Hida, Sei Ichi Tsujimura, Kazuo Mishima, Akira Yasukouchi, Sang Il Lee, Youhei Kinjyo, Manabu Miyahira, Melanopsin Gene Polymorphism I394T Is Associated with Pupillary Light Responses in a Dose-Dependent Manner, PLoS One, 10.1371/journal.pone.0060310, 8, 3, 2013.03, [URL], Background: Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) play an important role in non-image forming responses to light, such as circadian photoentrainment, light-induced melatonin suppression, and pupillary light response. Although it is known that there are some single nucleotide polymorphisms (SNPs) in the melanopsin (OPN4) gene in humans, the associations of the SNPs with non-image forming responses to light remains unclear. In the present study, we examined the associations of melanopsin gene polymorphisms with pupillary light response. Methods: Japanese university students (mean age: 21.0±1.7 years) with the genotypes of TT (n = 38), TC (n = 28) and CC (n = 7) at rs1079610 (I394T) located in the coding region participated in the present study. They were matched by age and sex ratio. Dark-adapted pupil size (<1 lx) was first measured. Then steady-state pupil size was measured during exposure to five lighting conditions (10 lx, 100 lx, 1000 lx, 3000 lx, 6000 lx in the vertical direction at eye level). Results: Significant interaction between the genotype of I394T (TT versus TC+CC) and luminance levels was found in pupil size. Under high illuminance levels (1000 lx, 3000 lx and 6000 lx), pupil sizes in subjects with the C allele were significantly smaller than those in subjects with the TT genotype. On the other hand, pupil size in subjects with the C allele under low illuminance (<1 lx) was significantly larger than that in subjects with the TT genotype. Percentages of pupil constriction under high illuminance levels were significantly greater in subjects with the C allele than in subjects with the TT genotype. Conclusions: Human melanopsin gene polymorphism I394T interacted with irradiance in association with pupil size. This is the first evidence suggesting a functional connection between melanopsin gene polymorphism and pupillary light response as an index of non-image forming response to light..|
|9.||樋口重和, 光の非視覚的作用 -光環境への適応-, 日本生理人類学会誌, 16, 1, 21-26, 2011.03, [URL].|
|10.||Shigekazu Higuchi, Yutaka Motohashi, Keita Ishibashi, Takafumi Maeda, Influence of eye colors of Caucasians and Asians on suppression of melatonin secretion by light, American Journal of Physiology - Heart and Circulatory Physiology, 10.1152/ajpregu.00355.2006, 292, 6, 2007.06, [URL], This experiment tested effects of human eye pigmentation depending on the ethnicity on suppression of nocturnal melatonin secretion by light. Ten healthy Caucasian males with blue, green, or light brown irises (light-eyed Caucasians) and 11 Asian males with dark brown irises (dark-eyed Asians) volunteered to participate in the study. The mean ages of the light-eyed Caucasians and dark-eyed Asians were 26.4 ± 3.2 and 25.3 ± 5.7 years, respectively. The subjects were exposed to light (1,000 lux) for 2 h at night. The starting time of exposure was set to 2 h before the time of peak salivary melatonin concentration of each subject, which was determined in a preliminary experiment. Salivary melatonin concentration and pupil size were measured before exposure to light and during exposure to light. The percentage of suppression of melatonin secretion by light was calculated. The percentage of suppression of melatonin secretion 2 h after the start of light exposure was significantly larger in light-eyed Caucasians (88.9 ± 4.2%) than in dark-eyed Asians (73.4 ± 20.0%) (P < 0.01). No significant difference was found between pupil sizes in light-eyed Caucasians and dark-eyed Asians. These results suggest that sensitivity of melatonin to light suppression is influenced by eye pigmentation and/or ethnicity..|
|11.||Shigekazu Higuchi, Yutaka Motohashi, Yang Liu, Akira Maeda, Effects of playing a computer game using a bright display on presleep physiological variables, sleep latency, slow wave sleep and REM sleep, Journal of Sleep Research, 10.1111/j.1365-2869.2005.00463.x, 14, 3, 267-273, 2005.09, [URL], Epidemiological studies have shown that playing a computer game at night delays bedtime and shortens sleeping hours, but the effects on sleep architecture and quality have remained unclear. In the present study, the effects of playing a computer game and using a bright display on nocturnal sleep were examined in a laboratory. Seven male adults (24.7 ± 5.6 years old) played exciting computer games with a bright display (game-BD) and a dark display (game-DD) and performed simple tasks with low mental load as a control condition in front of a BD (control-BD) and DD (control-DD) between 23:00 and 1:45 hours in randomized order and then went to bed at 2:00 hours and slept until 8:00 hours. Rectal temperature, electroencephalogram (EEG), heart rate and subjective sleepiness were recorded before sleep and a polysomnogram was recorded during sleep. Heart rate was significantly higher after playing games than after the control conditions, and it was also significantly higher after using the BD than after using the DD. Subjective sleepiness and relative theta power of EEG were significantly lower after playing games than after the control conditions. Sleep latency was significantly longer after playing games than after the control conditions. REM sleep was significantly shorter after the playing games than after the control conditions. No significant effects of either computer games or BD were found on slow-wave sleep. These results suggest that playing an exciting computer game affects sleep latency and REM sleep but that a bright display does not affect sleep variables..|
主要総説, 論評, 解説, 書評, 報告書等
|1.||樋口重和, 子どもの睡眠問題と光環境, 睡眠医療, 2017.12.|
|2.||樋口 重和, 李 相逸, 光のサーカディアンリズムとメラトニン分泌への作用の個人差, 照明学会誌，99(1)，20-24, 2015.01, [URL].|
|3.||樋口重和, 光とヒトのメラトニン抑制, 日本時間生物学雑誌, 2008.05.|
The Society for Light Treatment and Biological Rhythms
2003.04～2021.03, 日本生理人類学会, 評議員.
2003.04～2021.03, 日本生理人類学会, 理事.
2009.04～2017.12, 日本生理人類学会 感性研究部会, 部会長.
2013.04～2018.03, 日本生理人類学会 照明研究部会, 部会長.
2007.04, 日本睡眠学会, 評議員.
2005.04, 日本時間生物学会, 評議員.
2019.10.26～2019.10.27, 日本生理人類学会第80回大会, 座長（Chairmanship）.
2019.09.24～2019.09.27, The 14th International Congress of Physiological Anthropology, 実行委員.
2018.12.01～2017.12.01, 日本生理人類学会 光と生体リズム研究部会, 部会長.
2018.10.20～2018.10.21, 第25回日本時間生物学会, 座長（Chairmanship）.
2018.07.12～2018.07.14, 日本睡眠学会第43回定期学術集会, 座長（Chairmanship）.
2018.06.16～2018.06.17, 日本生理人類学会第77回大会, 大会長.
2017.08.21～2017.08.21, 日本生理人類学会 照明研究部会, 座長（Chairmanship）.
2017.10.28～2017.10.29, 第24回日本時間生物学会, 座長（Chairmanship）.
2017.06.24～2014.06.25, 日本生理人類学会第75回大会, 座長（Chairmanship）.
2016.09.22～2016.09.24, UNIST-JPA Joint Symposium 2016 on Anthropological and Physiological Research on Humans Living in Modern Society of the East Asia, 実行委員.
2015.10.27～2015.10.30, The 12th International Congress of Physiological Anthropology, 実行委員.
2015.10.27～2015.10.30, The 12th International Congress of Physiological Anthropology, 座長（Chairmanship）.
2015.03.20～2015.03.20, 日本生理人類学会 照明研究部会, 座長（Chairmanship）.
2015.03.14～2015.03.16, International Symposium on Human Adaptation to Environment and Whole-body Coordination, 実行委員.
2015.03.14～2015.03.16, International Symposium on Human Adaptation to Environment and Whole-body Coordination, 座長（Chairmanship）.
2014.11.21～2014.11.21, 応用生理人類学研究センター キックオフシンポジウム, 実行委員.
2014.11.07～2014.10.09, 第21回日本時間生物学会学術大会, 実行委員.
2014.09.04～2014.09.05, 2014年度日本生理人類学会夏期セミナー, 実行委員長.
2014.07.03～2014.07.04, 日本睡眠学会第39 回定期学術集会, 座長（Chairmanship）.
2014.06.21～2014.06.22, 日本生理人類学会第70回大会, 実行委員.
2014.06.21～2014.06.22, 日本生理人類学会第70回大会, 座長（Chairmanship）.
2014.05.15～2014.05.18, 国際人類学民族科学連合(IUAES), 座長（Chairmanship）.
2013.10.26～2013.10.27, 日本生理人類学会第69回大会, 座長（Chairmanship）.
2013.08.08～2013.08.10, 11th International Congress of Physiological Anthropology, 座長（Chairmanship）.
2013.06.08～2013.06.09, 日本生理人類学会第68回大会, 座長（Chairmanship）.
2012.06.28～2012.06.30, 日本睡眠学会第37回定期学術集会, 座長（Chairmanship）.
2012.05.12～2012.05.13, 日本生理人類学会第66回大会, 実行委員.
2011.06.11～2011.06.12, 日本生理人類学会第64回大会, 実行委員.
2011.03.03～2011.03.04, 第6回日本感性工学会春季大会, 座長（Chairmanship）.
2010.06.15～2010.06.16, 日本生理人類学会第62回大会, 座長（Chairmanship）.
2009.09.26～2009.09.27, 日本生理人類学会第61回大会, 実行委員.
2009.09.26～2009.09.27, 日本生理人類学会第61回大会, 座長（Chairmanship）.
2008.10.18～2008.10.19, 日本生理人類学会第59回大会, 実行委員長.
2008.06.07～2008.06.08, 日本生理人類学会第58回大会, 座長（Chairmanship）.
2003.04～2019.12, 日本生理人類学雑誌, 国内, 編集委員.
2005.04, Journal of PHYSIOLOGICAL ANTHROPOLOGY, 国際, 編集委員.
National University of Singapore, Singapore, 2019.09～2019.09.
Stem-cell and Brain Research Institute, France, 2019.08～2019.08.
National University of Singapore, Singapore, 2019.03～2019.03.
University of Basel , Switzerland, 2018.09～2018.09.
National University of Singapore, Singapore, 2018.03～2018.03.
Loughborough University, UnitedKingdom, 2017.09～2017.09.
カリフォルニア大学サンディエゴ校（UCSD）, UnitedStatesofAmerica, 2006.02～2006.03.
日本生理人類学会 優秀研究賞, 日本生理人類学会, 2015.05.
日本生理人類学会奨励賞, 日本生理人類学会, 2014.06.
国立精神神経センター精神保健研究所 青申賞, 2009.03.
日本時間生物学会 学術奨励賞, 2007.11.
日本生理人類学会 奨励賞, 1997.06.
2019年度～2021年度, 基盤研究(B), 代表, メラトニン受容体の遺伝子多型と夜勤時の光の生体影響.
2017年度～2019年度, 挑戦的研究（萌芽）, 代表, 子どもの高い光感受性と概日リズムを考慮した夜の光環境の指針開発に向けた研究.
2017年度～2021年度, 基盤研究(B), 分担, 子どものメラトニン分泌パタン改善に直結するシンプル・ストラテジーの提案と実践検証.
2015年度～2018年度, 基盤研究(A), 代表, 子どもの高い光感受性と概日リズムの夜型化・成熟に関する研究.
2013年度～2016年度, 基盤研究(A), 分担, 高齢者向けロコモ対策用ゲームの開発を通したゲームデザイン研究 .
2012年度～2016年度, 基盤研究(A), 分担, ゲノム情報・生理的多型性・行動からみた光環境における遺伝的及び可塑的適応性の評価.
2012年度～2014年度, 基盤研究(B), 代表, ヒトのメラノプシン遺伝子多型と生理機能:機能的潜在性の発現と環境適応能.
2012年度～2013年度, 挑戦的萌芽研究, 代表, 光の生理心理作用におけるプラセボ効果の検証.
2010年度～2011年度, 挑戦的萌芽研究, 代表, ヒト網膜のメラノプシンの遺伝子多型およびその機能的役割の解明.
2010年度～2012年度, 基盤研究(B), 分担, 子どもの睡眠健康増進のための生理人類学的介入研究.
2009年度～2011年度, 基盤研究(B), 代表, 光の生理心理作用の脳内機序と健康リスクへの適応.
2008年度～2011年度, 基盤研究(A), 分担, 現代の生活環境における行動履歴が生理的多型性に及ぼす影響、及びその適応性評価.
2006年度～2008年度, 基盤研究(B), 代表, 光に対する視覚的及び非視覚的な生体反応の生理的協関性と多型性.
2004年度～2004年度, 萌芽研究, 代表, 日照量の少ない東北地方における冬季の積雪が生体リズムの同調機構に果たす役割.
2003年度～2007年度, 基盤研究(S), 分担, 光と温熱の環境要因に対する生理的多型性とその適応能力.
2003年度～2003年度, 基盤研究(C), 代表, 海外における生理人類学の研究拠点の拡大にむけた企画調査.
2003年度～2003年度, 萌芽研究, 代表, 虹彩の色の多型が光に対する生体リズム同調に果たす役割の生理的解明にむけた基礎研究.
2001年度～2002年度, 奨励研究(A), 代表, IT社会の進展と生活習慣の夜型化が睡眠，生体リズム，精神的健康度に及ぼす影響.
1998年度～1999年度, 奨励研究(A), 代表, 照明の照度・色温度条件が知的作業能率及び覚醒水準の日内リズムに及ぼす影響.
2017.06～2018.02, 代表, 特異作業実施場所における照明環境改善研究（その５）.
2017.01～2019.03, 代表, 有機ＥＬディスプレイを対象とした感性・脳科学的アプローチに関する共同研究.
2016.12～2017.03, 代表, 特異作業実施場所における照明環境改善研究（その４）.
2013.10～2018.09, 代表, 概日時計に及ぼすL-セリンの影響に関する研究.
2009.09～2015.03, 代表, 美術館展示に関する感性・脳科学的アプローチに関する研究.