ClarifyingtheunderIyingmeGhanismsofschizophreniaviaoxidativestressinthebrain

• Project/Area Number: 22800048
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyushu University
• Principal Investigator: TAKAHIROA. Kato 九州大学, 先端融合医療レドックスナビ研究拠点, 特任助教 (70546465)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,146,000 (Direct Cost: ¥2,420,000、Indirect Cost: ¥726,000); Fiscal Year 2011: ¥1,508,000 (Direct Cost: ¥1,160,000、Indirect Cost: ¥348,000); Fiscal Year 2010: ¥1,638,000 (Direct Cost: ¥1,260,000、Indirect Cost: ¥378,000)
• Keywords: ミクログリア / 統合失調症 / 炎症免疫 / 酸化ストレス / フリーラジカル / 神経免疫 / モデル動物 / NADPHオキシターゼ / ミノサイクリン / 神経炎症

Research Abstract

Altered antioxidant status has been implicated in schizophrenia. Microglia, major sources of free radicals such as superoxide(. 02-), play crucial roles in various brain pathologies. Antioxidative effects of antipsychotics via modulating microglial superoxide generation have never been reported. Therefore, we herein investigated the effects of antipsychotics on the" 02 generation from phorbol-myristate-acetate(PMA)-stimulated rodent microglia by the electron spin resonance(ESR) spectroscopy and also examined the intracellular mechanism by intracellular Ca2+ imaging and immunostaining. Neuronal damage induced by microglial activation was also investigated by the co-culture experiment.
Our results imply that aripiprazole may have psychotropic effects by reducing the microglial oxidative reactions and following neuronal reactions, which puts forward a novel therapeutic hypothesis in schizophrenia research.

Research Products

• [Journal Article] Aripiprazole inhibits superoxide generation from phorbolmyristateacetate(PMA) stimulated microglia in vitro : implication forantioxidative psychotropic actions via microglia (2011)
  • Author(s): Kate TA, Monji A, Yasukawa K, Mizoguchi Y, Horikawa H, Seki Y, Hashioka S, Hah YH, Kasai M, Sonoda N, Hirata E, Maeda Y, Inoguchi T, Utsumi H, Kanba S
  • Journal Title: Schizophrenia Research Volume: 129(2-3) Pages: 172-182
• [Journal Article] Antiinflammatory properties of antipsychotics via microglia modulations ; Are antipsychotics a' fire extinguisher' in the brain of schizophrenia (2011)
  • Author(s): Kate TA, Monji A, Mizoguchi Y, Hashioka S, Horikawa H, Seki Y, Kasai M, Utsumi H, Kanba S
  • Journal Title: MiniReviews in Medicinal Chemistry Volume: 11(7) Pages: 565-574
• [Journal Article] Possible Role of BDNFInduced Microglial Intracellular Ca2+ Elevation in the Pathophysiology of Neuropsychiatric Disorders (2011)
  • Author(s): Mizoguchi Y, Monji A, Kate TA, Horikawa H, Seki Y, Kasai M, Kanba S, Yamada S
  • Journal Title: MiniReviews in Medicinal Chemistry Volume: 11(7) Pages: 575-581
• [Journal Article] Visual and auditory hallucinations during normal use of paroxetine for treatment of major depressive disorder (2011)
  • Author(s): Monji A, Kate T, Mizoguchi Y, Horikawa H, Seki Y, Kanba S
  • Journal Title: J Neuropsychiatry Cl in Neurosci Volume: 23(4)
• [Journal Article] Are Japan' s hikikomori and depression in young people spreading abroad? (2011)
  • Author(s): Kato TA, Shinfuku N, Sartorius N, Kanba S
  • Journal Title: The Lancet Volume: 378 Pages: 1070-1070
• [Journal Article] Introducing the Concept of Modern Depression in Japan ; an International Case Vignette Survey (2011)
  • Author(s): Kato TA, Shinfuku N, Fujisawa D, Tate no M, Ishida T, Akiyama T, Sartorius N, Tee AR, Choi TY, Wand APF, Balhara YPS, Chang JPC, Chang RYF, Shadloo B, Ahmed HU, Lerthattasilp T, UmeneNakano W, Horikawa H, Matsumoto R, Kuga H, Tanaka M, Kanba S
  • Journal Title: Journal of Affective Disorders Volume: 135(1-3) Pages: 66-76
• [Journal Article] 精神疾患における脳内炎症免疫機構の意義-統合失調症のミクログリア仮説 (2011)
  • Author(s): 加藤隆弘, 門司晃, 神庭重信
  • Journal Title: 細胞工学 Volume: 30(10) Pages: 1046-1053
• [Journal Article] ミクログリアの機能から見た統合失調症.特集脳の機能と統合失調症一新たな診断と治療への展望一 (2011)
  • Author(s): 加藤隆弘
  • Journal Title: 精神科治療学 Volume: 26(12) Pages: 1571-1580
• [Journal Article] Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction? (2011)
  • Author(s): Watabe M, Kato TA, Monji A, et al
  • Journal Title: Psychopharmacology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Neuroinflammation in schizophrenia especially focused on the role of microglia (2011)
  • Author(s): Monji A, Kato TA, Mizoguchi Y, et al
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: (In press)
  • Peer Reviewed
• [Journal Article] Aripiprazole inhibits superoxide generation from phorbol-myristate-acetate (PMA)-stimulated microglia in vitro : implication for antioxidative psychotropic actions via microglia (2011)
  • Author(s): Kato TA, Monji A, Yasukawa K, et al
  • Journal Title: Schizophrenia Research Volume: 129(2-3) Pages: 172-182
  • Peer Reviewed
• [Journal Article] Anti-inflammatory properties of antipsychotics via microglia modulations ; Are antipsychotics a 'fire extinguisher' in the brain of schizophrenia? (2011)
  • Author(s): Kato TA, Monji A, Mizoguchi Y, et al
  • Journal Title: Mini-Eeviews in Medicinal Chemistry Volume: 11(7) Pages: 565-574
  • Peer Reviewed
• [Journal Article] Anti-inflammatory properties of antipsychotics via microglia modulations ; Are antipsychotics a 'fire extinguisher' in the brain of schizophrenia? (2011)
  • Author(s): Mizoguchi Y, Monji A, Kato TA, et al
  • Journal Title: Mini-Reviews in Medicinal Chemistry Volume: 11(7) Pages: 575-581
  • Peer Reviewed
• [Journal Article] Visual and auditory hallucinations during normal use of paroxetine for treatment of major depressive disorder (2011)
  • Author(s): Monji A, Kato T, Mizoguchi Y, et al
  • Journal Title: J Neuropsychiatry Clin Neurosci Volume: 23(4)
  • Peer Reviewed
• [Journal Article] Are Japan's hikikomori and depression in young people spreading abroad? (2011)
  • Author(s): Kato TA, Shinfuku N, Sartorius N, Kanba S
  • Journal Title: The Lancet Volume: 378 Pages: 1070-1070
  • Peer Reviewed
• [Journal Article] Does the 'hikikomori' syndrome of social withdrawal exist outside Japan? A preliminary international investigation (2011)
  • Author(s): Kato TA, Tateno M, Shinfuku N, et al
  • Journal Title: Social Psychiatry and Psychiatric Epidemiology Volume: (In press)
  • Peer Reviewed
• [Journal Article] ミクログリアの機能から見た統合失調症 (2011)
  • Author(s): 加藤隆弘
  • Journal Title: 精神科治療学 Volume: 26(12)(総説) Pages: 1571-1580
• [Journal Article] Aripiprazole inhibits superoxide generation from phorbol-myristate-acetate (PMA)-stimulated microglia in vitro : implication for antioxidative psychotropic actions via microglia. (2011)
  • Author(s): Kato TA, Monji A, Yasukawa K, et al.
  • Journal Title: Schizophrenia Research Volume: (In press)
  • Peer Reviewed
• [Journal Article] Anti-inflammatory properties of antipsychotics via microglia modulations ; Are antipsychotics a 'fire extinguisher' in the brain of schizophrenia? (2011)
  • Author(s): Kato TA, Monji A, Mizoguchi Y, et al.
  • Journal Title: Mini-Reviews in Medicinal Chemistry Volume: (In press)
  • Peer Reviewed
• [Journal Article] mpact of biopsychosocial factors on psychiatric training in Japan and overseas : Are psychiatrists oriented to mind, brain, or sociocultural issues (2010)
  • Author(s): Kato TA, Tate no M, Nakano Y, Balhara YPS, Tee AR, Fujisawa D, Sasaki R, Ishida 1, Kanba S
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 64(5) Pages: 520-530
• [Journal Article] Development of two-hour suicide intervention program among medical residents : First pilot trial (2010)
  • Author(s): Kato TA, Suzuki Y, Sate R, Fujisawa D, Uehara K, Hashimoto N, Sawayama Y, Hayashi J, Kanba S, Otsuka K
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 64(5) Pages: 531-540
• [Journal Article] Attitudes of early career psychiatrists in Japan toward child and adolescent psychiatry and their career decision (2010)
  • Author(s): Tateno M, Kate T, Nakano W, Tee AR, Nakagawa A, Miyajima K, Kanba S, Nakamura J, Saito T
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 64(2) Pages: 199-201
• [Journal Article] Differences in the preferred route of administration of haloperidol for acute schizophrenia among young psychiatrists in two regions of Japan (2010)
  • Author(s): Tateno M, Kate T, Nakano W, Kanba S, Nakamura J, Saito T
  • Journal Title: Asian Journal of Psychiatry Volume: 3 Pages: 60-63
• [Journal Article] Successful treatment of chronic urticaria with a Japanese herbal medicine, yokukansan (2010)
  • Author(s): Kato S, Kate TA, Nishie H, Nishima 5, Iwanaga T, Monji A, Nakano M, Takeshita H, Furue M
  • Journal Title: Journal of Dermatology Volume: 37(12) Pages: 1066-1067
• [Journal Article] Inhibitory effects of SSRIs on IFN y induced microglial activation through the regulation of intracelluar calcium (2010)
  • Author(s): Horikawa H, Kate TA, Mizoguchi Y, Monji A, Seki I, Gotoh L, Ohkuri I, Yonaha M, Ueda T, Hashioka S, Kanba S
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34 Pages: 1306-1316
• [Journal Article] 精神疾患におけるミクログリアを介した神経免疫仮説 (2010)
  • Author(s): 加藤隆弘
  • Journal Title: 日本生物学的精神医学会誌(旧:脳と精神の医学) Volume: 21(4) Pages: 229-236
  • NAID: 130005395340
• [Journal Article] Inhibitory effects of SSRIs on IFN-γ induced microglial activation through the regulation of intracelluar calcium. (2010)
  • Author(s): Horikawa H, Kato TA, Mizoguchi Y, et al.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. Volume: 34 Pages: 1306-1316
  • Peer Reviewed
• [Journal Article] Impact of biopsychosocial factors on psychiatric training in Japan and overseas : Are psychiatrists oriented to mind, brain, or sociocultural issues? (2010)
  • Author(s): Kato TA, Tateno M, Nakano Y, et al.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 64(5) Pages: 520-530
  • Peer Reviewed
• [Journal Article] Development of two-hour suicide intervention program among medical residents : First pilot trial. (2010)
  • Author(s): Kato TA, Suzuki Y, Sato R, et al.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 64(5) Pages: 531-540
  • Peer Reviewed
• [Journal Article] Successful treatment of chronic urticaria with a Japanese herbal medicine, yokukansan. (2010)
  • Author(s): Kato S, Kato TA, Nishie H, et al.
  • Journal Title: Journal of Dermatology Volume: 37(12) Pages: 1066-1067
  • Peer Reviewed
• [Journal Article] Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction? Psychopharmacology
  • Author(s): Watabe M*, Kate TA C, Monji A, Horikawa H, Kanba S
  • Journal Title: These authors equally contributed to this work Volume: (in press)
• [Journal Article] Neuroinflammationin schizophrenia especially focused on the role of microglia. Progress in NeuroPsychopharmacology & Biological Psychiatry(in press) Neuroinflammationin schizophrenia especially focused on the role of microglia. Progress in NeuroPsychophar
  • Author(s): Monji A, Kate TA, Mizoguchi Y, Horikawa H, Seki Y, Kasai M, Yamauchi Y, Yamada S, Kanba S
  • Journal Title: Progress in NeuroPsychopharmacology & Biological Psychiatry Volume: (in press)
• [Journal Article] Does the' hikikomori' syndrome of social withdrawal exist outside Japan? A preliminary international investigation
  • Author(s): Kato TA, Tate no M, Shinfuku N, Fujisawa D, Tee AR, Sartorius N, Akiyama T, Ishida T, Choi TV, Balhara YPS, Matsumoto R, UmeneNakano W, Fu j imura Y, Wand A, Chang JPC, Chang RYF, Shadloo B, Ahmed HU, Lerthattasilp T, Kanba S
  • Journal Title: Social Psychiatry and Psychiatric Epidemiology Volume: (in press)
• [Presentation] 現代のうつ病は日本独自の疾患か?-ビネット症例を用いた国際比較調査-.シンポジウム「文化の変遷とうつ病」 (2011)
  • Author(s): 加藤隆弘,新福尚隆,神庭重信
  • Organizer: 第18回多文化間精神医学会学術総会
  • Place of Presentation: トラストシティカンファレンス・丸の内,東京
  • Year and Date: 2011-10-01
• [Presentation] 現代のうつ病は日本独自の疾患か?-ビネット症例を用いた国際比較調査- (2011)
  • Author(s): 加藤隆弘, 新福尚隆, 神庭重信
  • Organizer: 第18回多文化間精神医学会学術総会
  • Place of Presentation: 丸の内,東京
  • Year and Date: 2011-10-01
• [Presentation] Prevalence, Diagnosis and Treatment of Hikikomori : Psychiatrists' impressions cross cultures Regular Symposium : Is Hikikomori a Japanese Culture唯ound Syndrome of Social Withdrawal or a Globally Prevalent New Diagnosis/Symptom associated with Sociocultur (2011)
  • Author(s): Kato TA, Shinfuku N, Kanba S
  • Organizer: 15th World Congress of Psychiatry
  • Place of Presentation: Buenos Aires, Argentina
  • Year and Date: 2011-09-19
• [Presentation] Prevalence, Diagnosis and Treatment of Hikikomori : Psychiatrists' impressions cross cultures (2011)
  • Author(s): Kato TA, Shinfuku N, Kanba S
  • Organizer: 15th World Congress of Psychiatry 2011
  • Place of Presentation: Buenos Aires, Argentina
  • Year and Date: 2011-09-19
• [Presentation] ミノサイクリンが信頼行動に及ぼす影響-ミクログリア仮説による検討- (2011)
  • Author(s): 渡部幹, 加藤隆弘
  • Organizer: 日本社会心理学会第52回大会
  • Place of Presentation: 名古屋大学全学教育棟,名古屋
  • Year and Date: 2011-09-18
• [Presentation] Minding not only neurons but also microglia-Digging up unconscious roles of microglia on our social activities (2011)
  • Author(s): Kato TA, Watabe M, Mon j i A, Kanba S
  • Organizer: Research Session' On Neurons and Noise', 12th International Congress of Neuropsychoanalysis
  • Place of Presentation: RADIALSYSTEM V, Berlin, Germany
  • Year and Date: 2011-06-26
• [Presentation] Minding not only neurons but also microglia-Digging up unconscious roles of microglia on our social activities- (2011)
  • Author(s): Kato TA, Watabe M, Monji A, Kanba S
  • Organizer: 12th International Congress of Neuropsychoanalysis
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2011-06-26
• [Presentation] Neuro-immunological hypothesis of schizophrenia via microglia. Session of" immune disorders (2011)
  • Author(s): Kato TA
  • Organizer: ESF-JSPS Frontier Science Conference for Young Researchers 2011-Cutting Edge Immunology and its Clinical Application
  • Place of Presentation: Apollo Hotel de Beyaerd, Hulshort, The Netherlands
  • Year and Date: 2011-03-04
• [Presentation] Neuro-immunological hypothesis of schizophrenia via microglia. (2011)
  • Author(s): Kato TA
  • Organizer: ESF-JSPS Frontier Science Conference for Young Researchers 2011-Cutting Edge Immunology and its Clinical Application.
  • Place of Presentation: Hulshort, The Netherlands
  • Year and Date: 2011-03-04
• [Presentation] 日本におけるひきこもりとネット依存一国際比較文化の視点から (2011)
  • Author(s): 加藤隆弘
  • Organizer: 和歌山大学保健管理センター・デイケア室新設記念シンポジウムー「ひきこもりとネット依存」
  • Place of Presentation: 和歌山フォルテワジマ,和歌山
  • Year and Date: 2011-02-19
• [Presentation] Aripiprazole inhibits superoxide generation from phorbolmyristateacetate(PMA) stimulated microglia in vitro (2011)
  • Author(s): Kato TA, Monji A, Yasukawa K, Mizoguchi Y, Horikawa H, Seki Y, Hashioka S, Kasai M, Sonoda N, Hirata E, Maeda Y, Inoguchi T, Utsumi H, Kanba S
  • Organizer: 16th JSPS Coreto-Core Seminar Winter School in Fukuoka
  • Place of Presentation: Lake Side Hotel Hisayama, Fukuoka
  • Year and Date: 2011-01-08
• [Presentation] Minocycline, an antibiotic with inhibitory effects of microglial activation, sharpens sense of trust in social interaction (2010)
  • Author(s): Kato TA, Watabe M, Monji A, Horikawa H, Kanba S
  • Organizer: Neuroscience Meeting
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2010-11-14
• [Presentation] Minocycline, an antibiotic with inhibitory effects of microglial activation, sharpens sense of trust in social interaction. (2010)
  • Author(s): Kato TA, Watabe M, Monji A, et al
  • Organizer: Neuroscience Meeting 2010
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2010-11-14
• [Presentation] 精神疾患におけるミクログリアを介した神経免疫仮説.シンポジウム「精神疾患と神経免疫」 (2010)
  • Author(s): 加藤隆弘
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: リーガロイヤルホテル小倉,北九州
  • Year and Date: 2010-10-07
• [Presentation] 精神疾患におけるミクログリアを介した神経免疫仮説.(シンポジウム「精神疾患と神経免疫」) (2010)
  • Author(s): 加藤隆弘
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: リーガロイヤルホテル小倉,北九州
  • Year and Date: 2010-10-07
• [Presentation] ミノサイクリンが信頼行動に及ぼす影響一ミクログリア仮説による検討 (2010)
  • Author(s): 渡部幹,加藤隆弘
  • Organizer: 日本社会心理学会第52回大会
  • Place of Presentation: 名古屋大学全学教育棟,名古屋
  • Year and Date: 2010-09-18
• [Presentation] Cytokines, Free Radicals and Schizophrenia-Microglia Hypothesis of Schizophrenia (2010)
  • Author(s): Kato TA, Monji A, Kanba S
  • Organizer: World Psychiatric Association(WPA) International Congress
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-09-04
• [Presentation] nternational Questionnaire Survey with Case Vignettes of Japan' s Youth Depression and Hikikomori-How the Cases are evaluated by Foreign Psychiatrists? Symposium : Sociocultural Changes and Mental Health among Younger Generations in Asia(Organized by Shin (2010)
  • Author(s): Kato TA
  • Organizer: World Psychiatric Association(WPA) International Congress
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-09-02
• [Presentation] Bridging Hypothesis between Psychoanalytic" Death Drive" and Basic Neuroscience Do microglia unconsciously drive our painful emotions (2010)
  • Author(s): Kato TA, Monji A, Kanba S
  • Organizer: 11th International Congress of Neuropsychoanalysis
  • Place of Presentation: University of Washington, Seattle, WA, USA
  • Year and Date: 2010-07-24
• [Presentation] Bridging Hypothesis between Psychoanalytic "Death Drive" and Basic Neuroscience-Do microglia unconsciously drive our painful emotions?-. (2010)
  • Author(s): Kato TA, Monji A, Kanba S
  • Organizer: 11th International Congress of Neuropsychoanalysls is
  • Place of Presentation: University of Washington, Seattle, WA, USA
  • Year and Date: 2010-07-24
• [Presentation] Antioxidative effect of aripiprazole, a novel unique antipsychotic, via inhibiting superoxide generation from PMA-stimulated microglia (2010)
  • Author(s): Kate T, Monji A, Yasukawa K, MizoguchiY, Horikawa H, Seki Y, Yonaha M, Hashioka S, Han YH, Utsumi H, Kanba S
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-07
• [Presentation] Antioxidative effect of aripiprazole, a novel unique antipsychotic, via inhibiting superoxide generation from PMA-stimulated microglia. (2010)
  • Author(s): Kato TA, Monji A, Yasukawa K, et al.
  • Organizer: CINP (Collegium Internationale Neuro-Psychopharmacologicum) meeting 2010
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-07
• [Presentation] ミノサイクリンが信頼行動に及ぼす影響一ミクログリア仮説による検討 (2010)
  • Author(s): 渡部幹,加藤隆弘,坪井翔
  • Organizer: 日本社会心理学会第51回大会
  • Place of Presentation: 広島大学,東広島
• [Book] 「ミクログリア」.現代精神医学事典 (2011)
  • Author(s): 加藤隆弘
  • Total Pages: 988
  • Publisher: 弘文堂
• [Book] 「精神分析(脳科学との接点)」.現代精神医学事典 (2011)
  • Author(s): 加藤隆弘
  • Publisher: 弘文堂
• [Book] 「6.ミクログリアと精神疾患」. II.分子生物学, B,細胞『専門医のための精神科臨床リュミエール』16巻一精神科医のための脳科学:これだけは知っておきたい基礎知識一 (2010)
  • Author(s): 加藤隆弘
  • Publisher: 中山書店
• [Book] 専門医のための精神科臨床リュミエール16巻-精神科医のための脳科学(神庭重信・加藤忠史編集)(ミクログリアと精神疾患(178-179頁)) (2010)
  • Author(s): 加藤隆弘(分担)
  • Total Pages: 328
  • Publisher: 中山書店(東京)
• [Remarks]
  • URL: http://redoxnavi.kyushu-u.ac.jp/
• [Remarks] 九州大学先端融合医療レドックスナビ研究拠点ホームページ
• [Remarks] 九州大学精神科ホームページ
• [Remarks] 九州大学先端融合医療レドックスナビ研究拠点
  • URL: http://redoxnavi.com/
• [Remarks] 九州大学大学院医学研究院精神病態医学
  • URL: http://www.med.kyushu-u.ac.jp/psychiatry/
• [Remarks] 九州大学先端融合医療レドックスナビ研究拠点
  • URL: http://redoxnavi.com/
• [Remarks] 九州大学大学院医学研究院 精神病態医学
  • URL: http://www.med.kyushu-u.ac.jp/psychiatry/