Generation of biological models with AD / HD patients induced iPS cells

• Project/Area Number: 24650192
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kobe University (2013-2014); Tohoku University (2012)
• Principal Investigator: SORA Ichiro 神戸大学, 医学(系)研究科(研究院), 教授 (40322713)
• Co-Investigator(Kenkyū-buntansha): KASAHARA Yoshiyuki 東北大学, 大学院医学系研究科, 助教 (20511835)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: モノアミン / ドーパミン / メチルフェニデート

Outline of Final Research Achievements

To generate Attention Deficit Hyperactivity Disorder (AD / HD) patients induced pluripotent stem cells (iPS cells), the selection of patients with appropriate diagnostic criteria are important. Diagnostic criteria of DSM-IV was used for AD / HD without comorbid disorders. Such as autism spectrum syndrome were carefully excluded for the subjects. We generated iPS cells from healthy individuals and AD / HD patients. Dopaminergic nervous system in the AD / HD which is considered to midbrain cortical limbic system that projects from the ventral tegmental area to the nucleus accumbens and frontal cortex plays an important role. We have studied on the differentiation to distinguish the midbrain limbic dopaminergic neurons and the nigrostriatal dopaminergic ones induced from the iPS cells.

Research Products

• [Journal Article] Specific regions display altered grey matter volume in μ-opioid receptor knockout mice: MRI voxel-based morphometry. (2015)
  • Author(s): Sasaki K, Sumiyoshi A, Nonaka H, Kasahara Y, Ikeda K, Hall FS, Uhl GR, Watanabe M, Kawashima R, Sora I
  • Journal Title: Br J Pharmacol Volume: 172 Issue: 2 Pages: 654-667
  • DOI: 10.1111/bph.12807
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic Concentration of Lithium Stimulates Complement C3 Production in Dendritic Cells and Microglia via GSK-3 Inhibition. (2015)
  • Author(s): Yu Z, Ono C, Aiba S, Kikuchi Y, Sora I, Matsuoka H, Tomita H
  • Journal Title: Glia Volume: 63 Issue: 2 Pages: 257-270
  • DOI: 10.1002/glia.22749
  • Peer Reviewed
• [Journal Article] Attenuated methamphetamine-induced locomotor sensitization in serotonin transporter knockout mice is restored by serotonin 1B receptor antagonist treatment. (2015)
  • Author(s): Igari M, Shen H, Hagino Y, Fukushima S, Kasahara Y, Lesch K, Murphy D, George R Uhl, Ikeda K, Yaegashi N, Sora I
  • Journal Title: Behav Pharmacol Volume: 26 Issue: 1 and 2 - Special Issue Pages: 167-179
  • DOI: 10.1097/fbp.0000000000000120
  • Peer Reviewed
• [Journal Article] Decreased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) function in knockout mice affects aging of dopaminergic systems. (2014)
  • Author(s): Hall FS, Itokawa K, Schmitt A, Moessner R, Sora I, Lesch KP, Uhl GR
  • Journal Title: Neuropharmacology Volume: 76 Pages: 146-155
  • DOI: 10.1016/j.neuropharm.2013.07.031
  • Peer Reviewed
• [Journal Article] Haplotype analysis of the DISC1 Ser704Cys variant in Japanese suicide completers. (2014)
  • Author(s): Ratta-Apha W, Hishimoto A, Mouri K, Shiroiwa K, Sasada T, Yoshida M, Okazaki S, Supriyanto I, Asano M, Ueno Y, Shirakawa O, Sora I
  • Journal Title: Psychiatry Res Volume: 215 Issue: 1 Pages: 249-251
  • DOI: 10.1016/j.psychres.2013.11.007
  • Peer Reviewed
• [Journal Article] Association analysis of putative cis-acting polymorphisms of interleukin-19 gene with schizophrenia (2014)
  • Author(s): Okazaki, S., Watanabe, Y., Hishimoto, A., Sasada, T., Mouri, K., Shiroiwa, K., Eguchi, N., Ratta-Apha, W., Otsuka, I., Nunokawa, A., Kaneko, N., Shibnuya. M., Someya, T., Shirakawa, O., Sora, I.
  • Journal Title: Progress in Neuro-Psychopharmacology & Biological Psychiatry Volume: 50 Pages: 151-156
  • DOI: 10.1016/j.pnpbp.2013.12.006
  • Peer Reviewed
• [Journal Article] GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin- mediated inhibitory inputs from the bed nucleus of the stria terminalis (2014)
  • Author(s): Kudo T, Konno K, Uchigashima M, Yanagawa Y, Sora I, Minami M, Watanabe M
  • Journal Title: Eur. J. Neurosci Volume: (in press) Issue: 11 Pages: 1796-1809
  • DOI: 10.1111/ejn.12503
  • Peer Reviewed
• [Journal Article] A rare MIR138-2 gene variation is associated with schizophrenia in a Japanese population (2014)
  • Author(s): Watanabe, Y., Hishimoto, A., Shibuya, M., Nunokawa, A., Kaneko, N., Igeta, Egawa, J., Mouri, K., Sora, I., Someya, T.
  • Journal Title: Psychiatry Research Volume: 215 Issue: 3 Pages: 801-802
  • DOI: 10.1016/j.psychres.2013.12.029
  • Peer Reviewed
• [Journal Article] Developmental alterations in anxiety and cognitive behavior in serotonin transporter mutant mice. (2014)
  • Author(s): Sakakibara Y, Kasahara Y, Hall FS, Lesch KP, Murphy DL, Uhl GR, Sora I
  • Journal Title: Psychopharmacology Volume: 231 Issue: 21 Pages: 4119-4133
  • DOI: 10.1007/s00213-014-3554-x
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies a potent locus associated with human opioid sensitivity. (2014)
  • Author(s): Nishizawa D, Fukuda K, Kasai S, Hasegawa J, Aoki Y, Nishi A, Saita N, Koukita Y, Nagashima M, Katoh R, Satoh Y, Tagami M, Higuchi S, Ujike H, Ozaki N, Inada T, Iwata N, Sora I, Iyo M, Kondo N, Won MJ, Naruse N, Uehara-Aoyama K, Itokawa M, Koga M, Arinami T, Kaneko Y, Hayashida M, Ikeda K.
  • Journal Title: Mol Psychiatry Volume: 19(1) Issue: 1 Pages: 55-62
  • DOI: 10.1038/mp.2012.164
  • Peer Reviewed
• [Journal Article] Measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery. (2013)
  • Author(s): Kaneda Y, Ohmori T, Okahisa Y, Sumiyoshi T, Pu S, Ueoka Y,Takaki M,Nakagome K, Sora I
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 67(3) Issue: 3 Pages: 182-188
  • DOI: 10.1111/pcn.12029
  • Peer Reviewed
• [Journal Article] Evidence for shared genetic risk between methamphetamine-induced psychosis and schizophrenia (2013)
  • Author(s): 池田 匡志 他
  • Journal Title: Neuropsychopharmacology Volume: 38 Issue: 10 Pages: 1864-1870
  • DOI: 10.1038/npp.2013.94
  • Peer Reviewed
• [Journal Article] Association analysis of the DISC1 gene with schizophrenia in the Japanese population and DISC1 immunoreactivity in the postmortem brain. (2013)
  • Author(s): Ratta-Apha W, Hishimoto A, Mouri K, Shiroiwa K, Sasada T, Yoshida M, Supriyanto I, Ueno Y, Asano M, Shirakawa O, Togashi H, Takai Y, Sora I
  • Journal Title: Neurosci Res Volume: 77(4) Issue: 3 Pages: 222-227
  • DOI: 10.1016/j.psychres.2013.05.030
  • Peer Reviewed
• [Journal Article] Methamphetamine increases locomotion and dopamine transporter activity in dopamine D5 (2013)
  • Author(s): Hayashizaki S, Hirai S, Ito Y, Honda Y, Arime Y, Sora I, Okado H , Kodama T, Takada M.
  • Journal Title: PLoS ONE Volume: 8(10) Issue: 10 Pages: 1-8
  • DOI: 10.1371/journal.pone.0075975
  • Peer Reviewed
• [Journal Article] A short version of the measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery. (2013)
  • Author(s): Kaneda Y, Sora I
  • Journal Title: Schizophr Res Volume: 150(2-3) Issue: 2-3 Pages: 600-601
  • DOI: 10.1016/j.schres.2013.09.002
  • Peer Reviewed
• [Journal Article] Serotonergic involvement in the amelioration of behavioral abnormalities in dopamine transporter knockout mice by nicotine. (2013)
  • Author(s): Uchiumi O, Kasahara Y, Fukui A, Hall FS, Uhl GR, Sora I
  • Journal Title: Neuropharmacology Volume: 64 Pages: 348-356
  • DOI: 10.1016/j.neuropharm.2012.07.016
  • Peer Reviewed
• [Journal Article] Exclusive expression of VMAT2 in noradrenergic neurons increases viability of homozygous VMAT2 knockout mice (2013)
  • Author(s): Ohara A, Kasahara Y, Yamamoto H, Hata H, Kobayashi H, Numachi Y, Miyoshi I, Hall FS, Uhl GR, Ikeda K, Sora I
  • Journal Title: Biochem Biophys Res Commun Volume: 432 Issue: 3 Pages: 526-532
  • DOI: 10.1016/j.bbrc.2013.02.014
  • Peer Reviewed
• [Journal Article] Impaired Cliff Avoidance Reaction in Dopamine Transporter Knockout Mice (2013)
  • Author(s): Yamashita M, Sakakibara Y, Hall F, Numachi Y, Yoshida, S, Kobayashi H,Uchiumi O, Uhl George, Kasahara Y,Sora I
  • Journal Title: Psychopharmacology Volume: in press
  • Peer Reviewed
• [Journal Article] 痛み感受性の遺伝的要因 (2012)
  • Author(s): 井手聡一郎, 南雅文, 池田和隆
  • Journal Title: ペインクリニック Volume: 33(1) Issue: 1 Pages: 67-74
  • DOI: 10.1017/s1461145711001842
  • Peer Reviewed
• [Journal Article] Cortico-subcortical neuromodulation involved in the amelioration of prepulse inhibition deficits in dopamine transporter knockout mice. (2012)
  • Author(s): Arime Y, Kasahara Y, Hall FS, Uhl GR, Sora I
  • Journal Title: Neuropsychopharmacology Volume: 37 Issue: 11 Pages: 2522-2530
  • DOI: 10.1038/npp.2012.114
  • Peer Reviewed
• [Presentation] Functional recovery in patients with schizophrenia: predicting factors for work outcome. (2015)
  • Author(s): Sumiyoshi C, Takaki M, Okahisa Y, Sato T, Sora I, Harvey Philip D, Nuechterlein K, Subotnik K, Sumiyoshi T
  • Organizer: International Congress on Schizophrenia Research (ICOSR)
  • Place of Presentation: Colorado Springs
  • Year and Date: 2015-03-28 – 2015-04-01
• [Presentation] Differences in responsiveness between methamphetamine, nisoxetine and methylphenidate may reflect specific developmental characteristics in juvenile DAT KO mice. (2014)
  • Author(s): Kubo Y, Kasahara Y, Arime Y, Hall FS, Takamatsu Y, Ikeda K, Uhl GR, Sora I, Tomota H
  • Organizer: The Society for Neuroscience (SFN) 43th Annual Meeting
  • Place of Presentation: Washington DC
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Region-specific dendritic spine loss of pyramidal neurons in dopamine transporter knockout mice. (2014)
  • Author(s): Kasahara Y, Arime Y, Hall FS, Uhl GR, Tomita H, Sora I
  • Organizer: The Society for Neuroscience (SFN) 43th Annual Meeting
  • Place of Presentation: Washington DC
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Genome-wide association study identifies a potent locus associated with human opioid sensitivity. (2013)
  • Author(s): Nishizawa D, Fukuda K, Kasai S, Hasegawa J, Aoki Y, Nishi A, Saita N, Koukita Y, Nagashima M, Katoh R, Satoh Y, Tagami M, Higuchi S, Ujike H, Ozaki N, Inada T, Iwata N, Sora I, Iyo M, Kondo N, Won M, Naruse N, Uehara K, Itokawa M, Koga M, Arinami T, Kaneko Y, Hayashida M, Ikeda K
  • Organizer: European Human Genetics Conference 2013
  • Place of Presentation: Paris
• [Presentation] Methamphetamine induced changes of monoamine neurotransmission in 5-HT1B KO mice. (2013)
  • Author(s): Moriya Y, Kasahara Y, Hagino Y, Hall FS, Hen R, Ikeda K, Uhl GR, Sora I
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: Kyoto
• [Presentation] Association of HLA-DRB*01 and HLA-DRB*04 with schizophrenia in the Japanese population. (2013)
  • Author(s): Woraphat R, Mouri K, Shiroiwa K, Sasada T, Irwan S, Eguchi N, Okazaki S, Hishimoto A, Sora I
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: Kyoto
• [Presentation] Association study of KIF17 genes with schizophrenia in the Japanese population. (2013)
  • Author(s): Mouri K, Shiroiwa K, Yoshida M, Woraphat R, Eguchi N, Okazaki S, Fukutake M, Irwan S, Sasada T, Hishinoto A, Sora I
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: Kyoto
• [Presentation] Increased regional gray matter volume in μ-opioid receptor knockout mice as determined by mri-voxel-based morphometry. (2013)
  • Author(s): Sasaki K, Sumiyoshi A,Nonaka H, Hall F.S., Uhl G.R., Watanabe M, Kasahara Y, Ikedae K, Kasashima R, Sora I
  • Organizer: International Narcotics Research Conference 2013
  • Place of Presentation: Australia
• [Presentation] Critical period of inhibitory effect of methylphenidate on hyperactivity in dopamine transporter knockout mice. (2013)
  • Author(s): Takamatsu Y, Kubo Y, Nagasawa SY, Uhl GR, Sora I, Ikeda K
  • Organizer: 3rd Congress of Asian College of Neuropsychopharmacology
  • Place of Presentation: Peking
• [Presentation] Association study of BDNF with completed suicide in the Japanese population. (2013)
  • Author(s): Hishimoto A, Woraphat R, Shiroiwa K, Sora I
  • Organizer: American Society of Human Genetics 2013 Annual Meeting
  • Place of Presentation: Boston
• [Presentation] Genetic vulnerability of drug addiction (2013)
  • Author(s): Sora I
  • Organizer: CINP Special Congress on Addiction
  • Place of Presentation: Kuala Lumpur
  • Invited
• [Presentation] Special Lecture: Animal models of mental disorders. (2012)
  • Author(s): Sora I
  • Organizer: Northeast Normal University Seminar
  • Place of Presentation: Changchun, China
  • Invited
• [Presentation] Genetic vulnerability of methamphetamine addiction. (2012)
  • Author(s): Sora I
  • Organizer: The 16th International Society for Biomedical Research on Alcoholism (ISBRA) World Congress
  • Place of Presentation: Sapporo, Japan
  • Invited
• [Presentation] 中枢刺激薬作用機序から知るAD/HDの病態メカニズム (2012)
  • Author(s): 曽良一郎
  • Organizer: 第22回日本臨床精神神経薬理学会・第42回日本神経精神薬理学会合同年会
  • Place of Presentation: 宇都宮
  • Invited
• [Presentation] 動物実験研究の意義と将来 -基礎から応用、隣接領域まで-
  • Author(s): 曽良一郎
  • Organizer: 日本心理学会第76回大会
  • Place of Presentation: 東京
  • Invited
• [Book] The role of serotonin in the effects of psychostimulant drugs: Behavioral studies of addiction-and abuse-related phenotypes. (2013)
  • Author(s): Moriya Y, Hall FS, Sora I
  • Publisher: Nova Science Publishers
• [Book] Serotonin: Biosynthesis, Regulation and Health Implications (2013)
  • Author(s): Moriya Y, Hall FS, Sora I
  • Publisher: Nova Science Publishers