Molecular mechanism of altered cannabinoid signaling in the pathophysiology of schizophrenia

• Project/Area Number: 21390332
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kanazawa University
• Principal Investigator: HASHIMOTO Takanori 金沢大学, 医学系, 准教授 (40249959)
• Co-Investigator(Kenkyū-buntansha): YAMADA Kazuo 理化学研究所, 分子精神科学研究チーム, 副チームリーダー (10322695) ; TODA Shigenobu 金沢大学, 附属病院, 講師 (00323006) ; YOSHIHARA Toru 金沢大学, 子どものこころの発達研究センター, 特任助教 (00401935) ; NISHIUCHI Takumi 金沢大学, 学際科学実験センター, 准教授 (20334790)
• Co-Investigator(Renkei-kenkyūsha): GEORGIEV Danko 金沢大学, 医学系, 博士研究員 (90532193)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 精神薬理学 / マリファナ / 死後脳 / Tetrahydrocannabinol / KCNS3 / サル / GABA伝達 / マイクロアレイ解析 / 思春期 / 遺伝子多型性 / 大麻 / 先行刺激抑制

Research Abstract

In the neocortex of juvenile mice that received chronic injections of a endocannabinoid receptor agonist, we failed to replicate expression changes of certain GABA-related genes that were observed in schizophrenia. However, juvenile monkeys chronically exposed to tetrahydrocannabinol, the main psychoactive constituent of marijuana, expression levels of KCNS3, which encodes PV neuron-specific potassium channel subunit Kv9. 3, were significantly decreased in the prefrontal cortex(PFC). KCNS3 mRNA levels were also decreased in the PFC of subjects with schizophrenia.

Research Products

• [Journal Article] Association study of the KCNJ3 gene as a susceptibility candidate for schizophrenia in the Chinese population (2012)
  • Author(s): Yamada K, Iwayama Y, Toyota T, Ohnishi T, Ohba H, Maekawa M, Yoshikawa T
  • Journal Title: Hum Genet Volume: 131 Pages: 443-51
  • Peer Reviewed
• [Journal Article] Deficit in transcriptional regulators in cortical parvalbumin neurons in schizophrenia (2012)
  • Author(s): Volk DW, Matsubara T, Li S, Sengupta EJ, Georgiev D, Minabe Y, Sampson A, Hashimoto T, Lewis DA
  • Journal Title: American Journal of Psychiatry Volume: (In press)
  • Peer Reviewed
• [Journal Article] A case control association study and cognitive function analysis of neuropilin and tolloid-like 1 gene and schizophrenia in the Japanese population (2011)
  • Author(s): Banno M, Koide T, Aleksic B, Yamada K, Kikuchi T, Kohmura K, Adachi Y, Kawano N, Kushima I, Ikeda M, Inada T, Yoshikawa T, Iwata N, Ozaki N
  • Journal Title: PLoS One Volume: 6(12)
  • Peer Reviewed
• [Journal Article] Lamina-specific Alterations in Cortical GABAA Receptor Subunit Expression in Schizophrenia Cerebral Cortex (2011)
  • Author(s): Beneyto M, Abbott A, Hashimoto T, Lewis DA
  • Volume: 21
  • Pages: 999-1101
  • Peer Reviewed
• [Journal Article] Association study of Nogo-related genes with schizophrenia in a Japanese case-control sample (2011)
  • Author(s): Jitoku D, Hattori E, Iwayama Y, Yamada K, Toyota T, Kikuchi M, Maekawa M, Nishikawa T, Yoshikawa T
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 156B Pages: 581-92
  • Peer Reviewed
• [Journal Article] Genome-wide association study of schizophrenia in Japanese population (2011)
  • Author(s): Yamada K, Iwayama Y, Hattori E, Iwamoto K, Toyota T, Ohnishi T, Ohba H, Maekawa M, Kato T, Yoshikawa T
  • Journal Title: PLoS One Volume: 6(6)
  • Peer Reviewed
• [Journal Article] Lamina-specific Alterations in Cortical GABAA Receptor Subunit Expression in Schizophrenia (2011)
  • Author(s): Beneyto M, Abbott A, Hashimoto T, Lewis DA
  • Journal Title: Cerebral Cortex Volume: 21 Pages: 999-1101
  • Peer Reviewed
• [Journal Article] Neurovascular coupling in the human somatosensory cortex a single trial study (2011)
  • Author(s): Kikuchi M, Shitamichi K, Ueno S,..., Hashimoto T(15人中13番目), ...
  • Journal Title: Neuroreport Volume: (In Press)
  • Peer Reviewed
• [Journal Article] Alteration of Cortical GABA Neurons and Network Oscillations in Schizophrenia (2010)
  • Author(s): Gonzalez-Burgos G, Hashimoto T, Lewis DA
  • Journal Title: Curr Psychiatry Rep Volume: 12(4) Pages: 335-344
• [Journal Article] 精神疾患の死後脳研究の成果と問題 (2010)
  • Author(s): 橋本隆紀, David A Lewis
  • Journal Title: 実験医学 Volume: 28(14) Pages: 2197-2204
• [Journal Article] 統合失調症と大脳皮質GABA伝達 (2010)
  • Author(s): 橋本隆紀, 松原拓郎, David A Lewis
  • Journal Title: 精神神経学雑誌 Volume: 112 Pages: 439-452
  • NAID: 10026960992
  • Peer Reviewed
• [Journal Article] 統合失調症の組織病理所見-前頭前野ニューロンの変化とその病態生理 (2010)
  • Author(s): 橋本隆紀, David A Lewis
  • Journal Title: 精神医学 Volume: 52 Pages: 341-350
• [Journal Article] Alteration of Cortical GABA Neurons and Network Oscillations in Schiz ophrenia (2010)
  • Author(s): Gonzalez-Burgos G, Hashimoto T, Lewis DA
  • Journal Title: Current Psychiatry Report Volume: 12 Pages: 335-344
• [Journal Article] Protracted Postnatal Developmental Trajectories of GABAA Receptor alpha1 and alpha2 Subunit Expression in Primate Prefrontal Cortex Biol Psychiatry (2009)
  • Author(s): Hashimoto T, Nugyen QL, Rotaru D, Keenan T, Arion D, Beneyto M, Gonzalez-Burgos G, Lewis DA
  • Volume: 65
  • Pages: 1015-23
  • Peer Reviewed
• [Journal Article] Altered Markers of Tonic Inhibition in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2009)
  • Author(s): Maldonado-Aviles JG, Curley AA, Hashimoto T, Lewis DA
  • Journal Title: Am J Psychiatry Volume: 166 Pages: 450-459
  • Peer Reviewed
• [Journal Article] Protracted Postnatal Developmental Trajectories of GABA-A Receptor alpha1 and alpha2 Subunit Expression in Primate Prefrontal Cortex (2009)
  • Author(s): Hashimoto, et al., 他7名
  • Journal Title: Biological Psychiatry 65 Pages: 1015-1023
  • Peer Reviewed
• [Journal Article] Deficit in transcriptional regulators in cortical parvalbumin neurons in schizophrenia American
  • Author(s): Volk DW, Matsubara T, Li S, Sengupta EJ, Georgiev D, Minabe Y, Sampson A, Hashimoto T, Lewis DA
  • Journal Title: J Psychiatry Volume: (in press)
  • Peer Reviewed
• [Presentation] Reduced mRNA levels for KCNS3 potassium channelα-subunit in parvalbumin-containing neurons in the prefrontal cortex of subjects with schizophrenia (2011)
  • Author(s): Georgiev D, Minabe Y, Lewis DA, Hashimoto T
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: Washington Convention Center(USA)
  • Year and Date: 2011-11-14
• [Presentation] Deficits in transcriptional regulators of cortical interneuron subpopulations in schizophrenia (2011)
  • Author(s): Volk DW, Matsubara T, Hashimoto T, Sengupta EJ, Lewis DA
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: Washington Convention Center(USA)
  • Year and Date: 2011-11-14
• [Presentation] Reduced mRNA levels for KCNS3 potassium channel α-subunit in parvalbumin-containing neurons in the prefrontal cortex of subjects with schizophrenia (2011)
  • Author(s): Gerogiev D, Minabe Y Lewis DA, Hashimoto T
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: Walter E Washington Convention Center USA
  • Year and Date: 2011-11-14
• [Presentation] Decreased KCNS3 K+Channel Alpha-subunit Gene Expression in the Prefrontal Cortex of Subjects with Schizophrenia (2011)
  • Author(s): Hashimoto T, Georgiev D, Minabe Y, Lewis DA
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-09-17
• [Presentation] Identification of Molecular Markers for Parvalbumin-or Somatostatin-Positive GABA Neurons in the Human Dorsolateral Prefrontal Cortex (2010)
  • Author(s): Georgiev D, Minabe Y, Lewis DA, Hashimoto T
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: San Diego Convention Center(USA)
  • Year and Date: 2010-11-15
• [Presentation] Identification of Molecular Markers for Parvalbumin-or Somatostatin-Positive GABA Neurons in the Human Dorsolateral Prefrontal Cortex (2010)
  • Author(s): Gerogiev D, Minabe Y, Lewis DA, Hashimoto T
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: サンディエゴコンベンションセンター(北米)
  • Year and Date: 2010-11-15
• [Presentation] New molecular markers of GABA neurons subsets in the human cerebral cortex (2010)
  • Author(s): Georgiev D, Minabe Y, Lewis DA, Hashimoto T
  • Organizer: 第37回日本脳科学会Keynote Presentation
  • Place of Presentation: 天津医科大学国際会議センター(中国)
  • Year and Date: 2010-10-17
• [Presentation] Identification of Molecular Markers for GABA Neuron Subsets in the Human Cerebral Cortex (2010)
  • Author(s): Georgiev D, Minabe Y, Lewis DA, Hashimoto T
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸コンベンションセンター(神戸)
  • Year and Date: 2010-09-03
• [Presentation] Identification of Molecular Markers for GABA Neuron Subsets in the Human Cerebral Cortex (2010)
  • Author(s): Gerogiev D, Minabe Y, Lewis DA, Hashimoto T
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-09-03
• [Presentation] 死後脳からみた統合失調症の病態 (2010)
  • Author(s): 橋本隆紀
  • Organizer: 第106回日本精神神経学会学術総会教育講演
  • Place of Presentation: 広島国際会議場(広島)
  • Year and Date: 2010-05-24
• [Presentation] 死後脳からみた統合失調症の病態 (2010)
  • Author(s): 橋本隆紀
  • Organizer: 第106回日本精神神経学会学術総会
  • Place of Presentation: 広島国際会議場(広島県) 招待講演
  • Year and Date: 2010-05-22
• [Presentation] New molecular markers of GABA neurons subsets in the human cerebral cortex (2010)
  • Author(s): Gerogiev D, Minabe Y, Lewis DA, Hashimoto T
  • Organizer: 第37回日本脳科学会
  • Place of Presentation: 天津医科大学国際会議センター(中国) 招待講演
• [Presentation] 霊長類前頭前野におけるGAGA受容体αサブユニット発現の発達変化 (2009)
  • Author(s): 橋本隆紀, Nguyen Q, Rotaru D, KeenanT, Arion D, Beneyto M, Gonzalez-Burgos G, Lewis D
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2009-09-17
• [Presentation] 霊長類前頭前野におけるGAGA受容体αサブユニット発現の発達変化 (2009)
  • Author(s): 橋本隆紀, 他7名
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-09-17
• [Presentation] 統合失調症の大脳皮質他領域におけるGABA関連遺伝子の発現解析 (2009)
  • Author(s): 橋本隆紀, Bazmi1 HH, Mirnics K, and Lewis DA
  • Organizer: 第36回日本脳科学会
  • Place of Presentation: 金沢大学医学部記念館(金沢)
  • Year and Date: 2009-06-12
• [Presentation] 統合失調症と大脳皮質GABA伝達障害 (2009)
  • Author(s): 橋本隆紀
  • Organizer: 第31回日本生物学的精神医学会シンポジウム「死後脳研究:その成果と課題」
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2009-04-24
• [Presentation] 統合失調症と大脳皮質GABA伝達障害 (2009)
  • Author(s): 橋本隆紀
  • Organizer: 第31回日本生物学的精神医学会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2009-04-24
• [Book] アメリカ・ピッツバーグ大学での死後脳研究について (2011)
  • Author(s): 橋本隆紀
  • Publisher: 光文社
• [Book] GABAニューロンと統合失調症 (2010)
  • Author(s): 橋本隆紀
  • Publisher: 中山書店
• [Book] 精神科リュミエール16:脳科学エッセンシャルGABAニューロンと統合失調症 (2010)
  • Author(s): 橋本隆紀
  • Total Pages: 3
  • Publisher: 中山書店