Research activity information

• Antioxidant effects of continuous intake of electrolyzed hydrogen water in healthy adults

  Kei Mizuno, Kyosuke Watanabe, Emi Yamano, Kyoko Ebisu, Kanako Tajima, Junzo Nojima, Yusuke Ohsaki, Shigeru Kabayama, Yasuyoshi Watanabe

  Chronic oxidative stress induces deterioration of health and a risk for the onset of various diseases. Previous clinical studies revealed that electrolyzed hydrogen water (EHW) is effective to reduce oxidative stress during hemodialysis in patients with chronic dialysis. In the present observational study, we investigated the antioxidant effects of a daily continuous intake of EHW in healthy adults. The concentrations of serum reactive oxygen metabolites-derived compounds (d-ROMs) and blood urea nitrogen in healthy volunteers (n = 64) who had a habit of intake over 500 mL/day of EHW at least 5 days a week for longer than 6 months were lower than those of age- and sex-matched controls (n = 470) without the habit of EHW intake. Oxidation stress index which the ratio between concentrations in d-ROMs and biological antioxidant potential was correlated with the serum concentration of high-sensitivity C-reactive protein or low-density lipoprotein cholesterol in the EHW group. These results suggest that the continuous intake of EHW induces antioxidant effects and may contribute to alleviate the risk of various oxidative stress-related dysfunctions and diseases in healthy adults.

  Nov. 2022, Heliyon, 8(11) (11), e11853, English, International magazine

  Scientific journal


• Developmental dysregulation of excitatory-to-inhibitory GABA-polarity switch may underlie schizophrenia pathology: A monozygotic-twin discordant case analysis in human iPS cell-derived neurons

  Michihiro Toritsuka, Hiroki Yoshino, Manabu Makinodan, Daisuke Ikawa, Sohei Kimoto, Kazuhiko Yamamuro, Kazuya Okamura, Wado Akamatsu, Yohei Okada, Takuya Matsumoto, Kazumichi Hashimoto, Yoichi Ogawa, Yasuhiko Saito, Kyosuke Watanabe, Chieko Aoki, Ryohei Takada, Shin-ichi Fukami, Kaori Hamano-Iwasa, Hideyuki Okano, Toshifumi Kishimoto

  Elsevier {BV}, Nov. 2021, Neurochemistry International, 150, 105179 - 105179, English

  Scientific journal


• Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals

  Kei Mizuno, Akihiro T. Sasaki, Kyosuke Watanabe, Yasuyoshi Watanabe

  Our double-blind, placebo-controlled study evaluated effects of ubiquinol, the reduced form of coenzyme Q10, on mild fatigue in healthy individuals experiencing fatigue in daily life that had continued for more than 1 and less than 6 months. The participants received 100-mg/day (Ubq100; age 44.0 ± 9.8 years; 14 females and 6 males) or 150-mg/day ubiquinol (Ubq150; age 40.4 ± 11.8 years; 14 females and 8 males) or placebo (Plc; age 41.3 ± 13.4 years; 13 females and 7 males) daily for 12 weeks. Measurements of subjective and objective fatigue were conducted by using questionnaires-based fatigue scales/visual analogue scales and autonomic nerve function/biological oxidation index, respectively, prior to the first dosing and every 4 weeks thereafter. Serum ubiquinol level increased three- to four-fold after 4 weeks and remained significantly higher than that after Plc administration throughout the intake period. Although a higher blood level of ubiquinol was observed with Ubq150 than with Ubq100, the difference was not statistically significant. In both Ubq100 and Ubq150 groups, subjective levels of fatigue sensation and sleepiness after cognitive tasks, which consisted of the modified Advanced Trail Making Test, the modified Stroop Color-Word Test, and the Digit Symbol Substitution Test, improved significantly compared with those in the placebo group, suggesting an anti-fatigue effect. The Ubq150 group demonstrated significant improvement compared with the Plc group regarding subjective level of relaxation after task, sleepiness before and after task, motivation for task, and serum level of oxidative stress. Correlation analysis between blood level of ubiquinol and each evaluated effect suggested a positive relationship with relaxation after task, motivation for cognitive task, and parasympathetic activity. The results of the study suggest that ubiquinol intake relieves mild fatigue in healthy individuals.

  {MDPI} {AG}, Jun. 2020, Nutrients, 12(6) (6), 1640 - 1640, English, International magazine

  Scientific journal


• Mental fatigue is linked with attentional bias for sad stimuli.

  Kyosuke Watanabe

  Previous studies have revealed that patients with chronic fatigue syndrome and affective disorders (such as depression and anxiety disorders) exhibit a vigilant attentional bias toward negative emotional stimuli. However, it remains unclear whether the change in an attentional bias for negative emotional stimuli can be induced by mental fatigue in healthy individuals. To address this question, we examined healthy participants' (n = 27) performance in a visual probe task and emotional Stroop task before and after the mental-fatigue-inducing task. We demonstrated that acute mental fatigue induced by the long-lasting working memory task led to the alteration of cognitive processing of negative emotional information in the healthy volunteers.

  Jun. 2019, Scientific reports

  Scientific journal


• PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10

  Kyosuke Watanabe, Satoshi Nozaki, Miki Goto, Ken-ichi Kaneko, Emi Hayashinaka, Satsuki Irie, Akira Nishiyama, Kazuaki Kasai, Kenji Fujii, Yasuhiro Wada, Kei Mizuno, Kenji Mizuseki, Hisashi Doi, Yasuyoshi Watanabe

  Elsevier {BV}, May 2019, Biochemical and Biophysical Research Communications, 512(3) (3), 611 - 615

  Scientific journal


• Cover Image, Volume 62, Issue 2

  Miki Goto, Akira Nishiyama, Takao Yamaguchi, Kyosuke Watanabe, Kenji Fujii, Yasuyoshi Watanabe, Hisashi Doi

  Wiley, Feb. 2019, Journal of Labelled Compounds and Radiopharmaceuticals, 62(2) (2), i - i, English

  Scientific journal


• Synthesis of 11 C-labeled ubiquinone and ubiquinol via Pd0 -mediated rapid C-[11 C]methylation using [11 C]methyl iodide and 39-demethyl-39-(pinacolboryl)ubiquinone.

  Kyosuke Watanabe

  To enable positron emission tomography (PET) imaging of the in vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q10 , their 11 C-radiolabeled counterparts were synthesized herein. 11 C-Labeled ubiquinone [11 C]-1 was realized by Pd-mediated rapid C-[11 C]methylation of [11 C]CH3 I with 39-demethyl-39-(pinacolboryl)ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [11 C]-1 using Na2 S2 O4 yielded 11 C-labeled ubiquinol [11 C]-2. The synthesis time and [11 C]CH3 I-based radiochemical yield of [11 C]-1 were within 36 minutes and up to 53%, while those of [11 C]-2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [11 C]-1 and [11 C]-2 were confirmed to be applicable for animal PET studies. The analytical values of [11 C]-1 and [11 C]-2 are as follows: radioactivity of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/μmol, radiochemical purity of greater than 99% and greater than 95%, and chemical purity of greater than 99% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to 11 C-radiolabeled ubiquinone and ubiquinol via a pinacolborane-substituted ubiquinone derivative. Each PET probe was used for molecular imaging using rats to investigate the in vivo kinetics and biodistribution of the coenzyme Q10 .

  Jan. 2019, Journal of labelled compounds & radiopharmaceuticals, 62(2) (2), 86 - 94, English, International magazine

  Scientific journal


• Imaging the passionate stage of romantic love by dopamine dynamics.

  Kyosuke Watanabe

  Using [(11)C]raclopride, a dopamine D2/D3 receptor antagonist, we undertook a positron emission tomography (PET) study to investigate the involvement of the dopaminergic neurotransmitter system when subjects viewed the pictures of partners to whom they were romantically attached. Ten subjects viewed pictures of their romantic partners and, as a control, of friends of the same sex for whom they had neutral feelings during the PET study. We administered [(11)C]raclopride to subjects using a timing for injecting the antagonist which had been determined in previous studies to be optimal for detecting increases in the amount of dopamine released by stimulation. The results demonstrated statistically significant activation of the dopaminergic system in two regions, the medial orbitofrontal cortex (mOFC) and medial prefrontal cortex, the former of which has been strongly implicated in a variety of rewarding experiences, including that of beauty and love. A positive correlation was obtained in mOFC between excitement levels and dopaminergic activation only in the love but not in the control condition.

  Apr. 2015, Frontiers in Human Neuroscience

  Scientific journal

• Identification of anti-fatigue factors for children and adolescents using fatigue transition networks

  水野 敬, 渡辺 恭介, 上土井 貴子

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Osaka Metropolitan University, 01 Apr. 2022 - 31 Mar. 2025

  本研究では、昨今の世界的パンデミックを引き起こしてきた新型コロナウイルス感染症に関する様々な国内における対策による社会環境変化の影響も踏まえたうえで、健常児童生徒と疲労関連疾患患児を対象に、主に自律神経機能と認知機能指標のデータ集積による心理生理学的特徴量を加味した疲労度遷移ネットワークの開発を基に、子どもの発達要素も踏まえた慢性疲労予防、疲労軽減・回復のための生活習慣等の抗疲労介入因子の同定を目指している。令和5年度は、前年度に比し、新型コロナウイルス感染症の拡大状況が一定の落ち着いた状況になり、児童生徒の新型コロナウイルス恐怖尺度のスコアも低下傾向を示した。前年度に引き続き、健常児童生徒と疲労関連疾患患児と保護者の協力を得て新型コロナウイルス恐怖尺度を含む質問票調査、自律神経機能検査および認知機能検査を実施した。その結果、疲労度の高い健常児童生徒は、前年度の平日の睡眠時間が短く休日前の睡眠時間が長く、自律神経機能の調節力と安静時副交感神経活動が低下しており、認知機能の中でも実行機能が低下している傾向がみられた。疲労関連疾患患児でも比較的同様の傾向がみられた。さらに、健常児童生徒群において、平日の睡眠時間の短縮傾向と朝食習慣、夜間コンビニエンスストア利用頻度、SNS利用頻度や平日の家族と過ごす時間とは密接な関連性が認められ、抗疲労のための睡眠時間の確保に重要な介入因子が明らかになりつつある。これらの介入により、疲労軽減、回復効果が見込める可能性を示唆するが、個々人における睡眠時間と生活習慣との関連性を紐解くための解析もさらに並行して推進する。自覚的感覚のみならず自律神経機能や認知機能といった客観的指標も加味して疲労、慢性疲労と関連する因子同定を図る本研究の社会医学的な意義、貢献度は高いといえる。