Exploration of treatment of hereditary vascular dementia CADASIL using patient-derived iPS cells and its model mice

• Project/Area Number: 23650182
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kyoto University
• Principal Investigator: IHARA Masafumi 京都大学, 医学研究科, 助教 (00372590)
• Project Period (FY): 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2011: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 血管性認知症 / CADASIL / iPS細胞 / Notch3

Research Abstract

Skin fibroblasts were isolated from three CADASIL patients with different mutations in Notch 3 gene. Three lines of iPS cells have been established by using the fibroblasts derived from one patient with CADASIL and endothelial cells and vascular smooth muscle cells were induced from the iPS cells. Their phenotypes were compared with those derived from normal controls. Furthermore, Notch 3 transgenic mice were obtained to investigate the pathogenesis of CADASIL in vivo and to compare the in vitro and in vivo phenotypes.

Research Products

• [Journal Article] Greater suitability of the Montreal Cognitive Assessment against the Mini-Mental State Examination in the detection of vascular cognitive impairment (2013)
  • Author(s): Ihara M, Okamoto Y, Takahashi R
  • Journal Title: J Stroke Cerebrovasc Dis Volume: 22(6) Issue: 6 Pages: 737-41
  • DOI: 10.1016/j.jstrokecerebrovasdis.2012.01.001
  • Peer Reviewed
• [Journal Article] Selective white matter abnormalities in a novel rat model of vascular dementia (2012)
  • Author(s): Kitamura A, Fujita Y, Oishi N, KalariaR N, Washida K, Maki T, Okamoto Y, HaseY, Yamada M, Takahashi J, Ito H, Tomimoto H, Fukuyama H, Takahashi R, Ihara M
  • Journal Title: Neurobiology of Aging Volume: 33 Issue: 5 Pages: 25-35
  • DOI: 10.1016/j.neurobiolaging.2011.10.033
  • NAID: 120003988349
  • Peer Reviewed
• [Journal Article] Cilostazol, a phosphodiesterase inhibitor, prevents no-reflow and hemorrhage in mice with focal cerebral ischemia (2012)
  • Author(s): Hase Y, Okamoto Y, Fujita Y, KitamuraA, Ito H, Maki T, Washida K, TakahashiR, Ihara M
  • Journal Title: Experimental Neurology Volume: 233 Issue: 1 Pages: 523-533
  • DOI: 10.1016/j.expneurol.2011.11.038
  • Peer Reviewed
• [Journal Article] Environmental enrichment ameliorated high fat diet-induced Aβdeposition and memory deficit in APP transgenic mice (2012)
  • Author(s): Maesako M, Uemura K, Kubota M, Kuzuya A, Sasaki K, Asada M, Watanabe K, Hayashida N, Ihara M, Ito H, ShimohamaS, Kihara T, Kinoshita A
  • Journal Title: Neurobiology of Aging Volume: 33 Issue: 5 Pages: 11-23
  • DOI: 10.1016/j.neurobiolaging.2011.10.028
  • NAID: 120003988394
  • Peer Reviewed
• [Journal Article] Cerebral hypoperfusion induces microinfarcts in cerebral amyloid angiopathy (2012)
  • Author(s): Okamoto Y, Yamamoto T, Kalaria RN, Senzaki H, Maki T, Hase Y, Kitamura A, Washida K, Yamada M, Ito H, Tomimoto H, Takahashi R, Ihara M
  • Journal Title: Acta Neuropathol Volume: 123(3) Issue: 3 Pages: 381-394
  • DOI: 10.1007/s00401-011-0925-9
  • Peer Reviewed
• [Journal Article] 18F-labeled Phenyldiazenyl Benzothiazole for invivo Imaging of Neurofibrillary Tangles in Alzheimer's Disease Brains (2012)
  • Author(s): Matsumura K, Ono M, Kimura H, Ueda M, Nakamoto Y, Togashi K, Okamoto Y, Ihara M, Takahashi R, Saji H
  • Journal Title: ACS Med Chem Lett Volume: 3(1) Issue: 1 Pages: 58-62
  • DOI: 10.1021/ml200230e
• [Journal Article] An autopsy case of SOD1-related ALS with TDP-43 positive inclusions (2011)
  • Author(s): Okamoto Y, Ihara M, Urushitani M, Yamashita H, Kondo T, Tanigaki A, Oono M, Kawamata J, Ikemoto A, Kawamoto Y, Takahashi R, Ito H
  • Journal Title: Neurology Volume: 77:1993-1995 Issue: 22 Pages: 1993-1995
  • DOI: 10.1212/wnl.0b013e31823a0cfc
  • Peer Reviewed
• [Journal Article] Lessons from a mouse model characterizing features of vascular cognitive impairment with white matter changes (2011)
  • Author(s): Ihara M, Tomimoto H
  • Journal Title: J Aging Res Volume: 2011 Pages: 978761-978761
  • DOI: 10.4061/2011/978761
  • Peer Reviewed
• [Journal Article] Clinicopathologic study on an ALS family with a heterozygous E478G optineurin mutation (2011)
  • Author(s): Ito H, Nakamura M, Komure O, Ayaki T, Wate R, Maruyama H, Nakamura Y, FujitaK, Kaneko S, Okamoto Y, Ihara M, Konishi T, Ogasawara K, Hirano A, Kusaka H, KajiR, Takahashi R, Kawakami H
  • Journal Title: Acta Neuropathologica Volume: 122 Issue: 2 Pages: 223-229
  • DOI: 10.1007/s00401-011-0842-y
  • Peer Reviewed
• [Journal Article] Watershed Infarcts in a multiple microembolic model of monkey (2011)
  • Author(s): Maki T, Wakita H, Mase M, Itagaki I, Saito N, Ono F, Adachi K, Ito H, Takahashi R, Ihara M, Tomimoto H
  • Journal Title: Neuroscience Letters Volume: 499 Issue: 2 Pages: 80-83
  • DOI: 10.1016/j.neulet.2011.05.036
  • NAID: 120003238944
  • Peer Reviewed
• [Journal Article] Co localization of 14-3-3 proteins with SOD1 in Lewy Body-like hyaline inclusions in familial amyotrophic lateral sclerosis cases and the animal model (2011)
  • Author(s): Okamoto Y, Shirakashi Y, Ihara M, Urushitani M, Oono M, Kawamoto Y, Yamashita H, Shimohama S, Kato S, Hirano A, Tomimoto H, Ito H, Takahashi R
  • Journal Title: PLoS One Volume: 6 Issue: 5 Pages: e20427-e20427
  • DOI: 10.1371/journal.pone.0020427
  • Peer Reviewed
• [Journal Article] Angiogenic roles of adreno medullin through VEGF induction (2011)
  • Author(s): Maki T, Ihara M, Fujita Y, Nambu T, Harada H, Ito H, Nakao K, Tomimoto H, Takahashi R
  • Journal Title: Neuroreport Volume: 22 Issue: 9 Pages: 442-447
  • DOI: 10.1097/wnr.0b013e32834757e4
  • Peer Reviewed
• [Journal Article] Phenyldiazenyl benzothiazole derivatives as probes for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains (2011)
  • Author(s): Matsumura K, Ono M, et al
  • Journal Title: Med Chem Comm Volume: 2 Issue: 7 Pages: 596-600
  • DOI: 10.1039/c1md00034a
  • Peer Reviewed
• [Journal Article] Rhodanine and thiohydantoin derivatives for detecting tau pathology in Alzheimer's brains (2011)
  • Author(s): Ono M, Hayashi S, et al
  • Journal Title: ACS Chem Neurosci Volume: 2 Issue: 5 Pages: 269-275
  • DOI: 10.1021/cn200002t
  • Peer Reviewed
• [Journal Article] Selective white matter pathology induces a specific impainnent in spatial working memory (2011)
  • Author(s): Coltman R, Spain A, et al
  • Journal Title: Neurobiol Aging Volume: 32 Issue: 12 Pages: 2324.e7-2324.e12
  • DOI: 10.1016/j.neurobiolaging.2010.09.005
  • Peer Reviewed
• [Journal Article] Angiogenic and vasoprotective effects of adrenomedullin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice (2011)
  • Author(s): Tomimoto H
  • Journal Title: Stroke Volume: 42(4) Issue: 4 Pages: 1122-8
  • DOI: 10.1161/strokeaha.110.603399
  • Peer Reviewed
• [Presentation] βアミロイドの血管依存性クリアランス (2011)
  • Author(s): 猪原匡史
  • Organizer: 第30回日本認知症学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-12
• [Presentation] 脳低灌流によりβアミロイドの血管依存性クリアランスが障害される (2011)
  • Author(s): 猪原匡史, 岡本洋子, 眞木崇州, 鷲田和夫, 伊東秀文, 冨本秀和, 高橋良輔
  • Organizer: 第30回日本認知症学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-11
• [Presentation] 皮質下血管性認知症患者におけるモントリオール認知評価スコアと身体活動度との相関 (2011)
  • Author(s): 猪原匡史
  • Organizer: 第30回日本認知症学会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-11
• [Presentation] Animal models forvascular cognitive impairment due tolarge vessel disease (2011)
  • Author(s): Masafumi Ihara
  • Organizer: Stroke Symposiumin National University of Singapore(Invited lecture)
  • Place of Presentation: Singapore
  • Year and Date: 2011-10-31
• [Presentation] Animal models for vascular cognitive impairment due to large vessel disease (2011)
  • Author(s): Masafumi Ihara
  • Organizer: STROKE SYMPOSIUM
  • Place of Presentation: Singapore(CELS Auditorium)
  • Year and Date: 2011-10-31
• [Presentation] Angiogenic andvasoprotective effects of adrenomedullin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice (2011)
  • Author(s): Masafumi Ihara
  • Organizer: Vas-Cog
  • Place of Presentation: Lille, France
  • Year and Date: 2011-09-14
• [Presentation] Poster review session. (2011)
  • Author(s): Masafumi Ihara
  • Organizer: Vas-Cog
  • Place of Presentation: Lille, France
  • Year and Date: 2011-09-13
• [Presentation] モントリオール認知評価法MoCAはMMSEよりも皮質下血管性認知障害の検出感度が高い (2011)
  • Author(s): 猪原匡史, 岡本洋子, 伊東秀文, 高橋良輔
  • Organizer: 第52回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18