An immunohistochemical study on nuclear bodies in neurodegenerativediseases with abnormal protein aggregates

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659184
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Niigata University
• Principal Investigator: TAKAHASHI Hitoshi 新潟大学, 脳研究所, 教授 (90206839)
• Co-Investigator(Kenkyū-buntansha): TOYOSHIMA Yasuko 新潟大学, 脳研究所, 准教授 (20334675)
• Co-Investigator(Renkei-kenkyūsha): ONODERA Osamu 新潟大学, 脳研究所, 教授 (20303167)
• Project Period (FY): 2011 – 2012
• Keywords: 脳 / 神経

Research Abstract

The kinetics of two nuclear bodies, PML and Cajal bodies, werestudied in multiple system atrophy (MSA) and sporadic amyotrophic lateral sclerosis (ALS),respectively. In MSA, in the nuclei of the pontine nuclei neurons, PML bodies were found tobe deformed in the presence of r-synuclein-positive intranuclear inclusions: the roundstructures changed to rod-like or linear abnormal ones. Statistically, the entire volume ofPML bodies was significantly decreased in MSA group (n=5) than in control group (n=5). InALS, in the nuclei of the lumbar anterior horn cells, the number of Cajal bodies was significantly decreased in ALS group (n=5: 8.06+/-4.41) than in control group (n=5:17.19+/-4.09). It is tempting to speculate that in MSA and ALS, these decreases of PML andCajal bodies, which are associated with neuronal viability, play an important role inneuronal cell death in relation to abnormalities of r-synuclein and TDP-43, respectively.

Research Products

• [Journal Article] Ubiquilinimmunoreactivity in cytoplasmic andnuclear inclusions in synucleinopathies,polyglutamine diseases and intranuclearinclusion body disease. (2012)
  • Author(s): Mori F, Tanji K, Odagiri S, ToyoshimaY, Yoshida M, Sasaki H, Kakita A,Takahashi H, Wakabayashi K.
  • Journal Title: ActaNeuropathol Volume: 124 Pages: 149-151
  • DOI: DOI:10.1007/s00401-012-0999-z
  • Peer Reviewed
• [Journal Article] Optineurin immunoreactivity in neuronalnuclear inclusions of polyglutaminediseases (Huntington's, DRPLA, SCA2,SCA3) and intranuclear insclusion bodydisease. (2012)
  • Author(s): Mori F, Tanji K, Toyoshima Y, YoshidaM,Kakita A, Takahashi H, Wakabayashi K.
  • Journal Title: Acta Neuropathol Volume: 123 Pages: 747-749
  • DOI: DOI:10.1007/s00401-012-0956-x
  • Peer Reviewed
• [Journal Article] Primary lateral sclerosis:upper-motor-predominant amyotrophiclateral sclerosis with frontotemporallobar degeneration immunohistochemicaland biochemicalanalyses of TDP-43. (2012)
  • Author(s): Kosaka T, Fu Y-J, Shiga A, Ishidaira H,Tan C-F, Tani T, Koike R, Onodera O,Nishizawa M, Kakita A, Takahashi H.
  • Journal Title: Neuropathology Volume: 32 Pages: 373-384
  • DOI: DOI:10.1111/j.1440-1789.2011.01271.x
  • Peer Reviewed
• [Journal Article] Co-occurrenceof argyrophilic grain disease insporadic amyotrophic lateral sclerosis. (2012)
  • Author(s): Soma K, Fu Y-J, Wakabayashi K, OnoderaO, Kakita A, Takahashi H.
  • Journal Title: Neuropathol Appl Neurobiol Volume: 38 Pages: 54-60
  • DOI: DOI:10.1111/j.1365-2990.2011.01175.x
  • Peer Reviewed
• [Journal Article] Molecular pathology and geneticadvances in amyotrophic lateralsclerosis: an emerging molecularpathway and the significance of glialpathology. (2011)
  • Author(s): Ince PG, Highley JR, Kirby J, WhartonSB, Takahashi H, Strong MJ, Shaw PJ.
  • Journal Title: Acta Neuropathol Volume: 122 Pages: 675-671
  • DOI: DOI:10.1007/s00401-011-0913-0
  • Peer Reviewed
• [Journal Article] Spinocerebellar ataxia type 2 (SCA2)is associated with TDP-43 pathology. (2011)
  • Author(s): Toyoshima Y, Tanaka H, Shimohata M,Kimura K, Morita T, Kakita A, TakahashiH.
  • Journal Title: Acta Neuropathol Volume: 122 Pages: 375-378
  • DOI: DOI:10.1007/s00401-011-0862-7
  • Peer Reviewed
• [Presentation] Neuropathology of amyotrophic lateral sclerosis-Discovery of TDP-43 and after that - (2012)
  • Author(s): Takahashi H.
  • Organizer: Seoul Neuropathology Forum - The Neuropathology Study Group of the Korean Society of Pathologists
  • Place of Presentation: Seoul
  • Year and Date: 2012-12-08
• [Presentation] Amyotrophic lateralsclerosis: a multisystem neuro-glialproteinopathy of TDP-43 (2011)
  • Author(s): Takahashi H.
  • Organizer: The 7th AisiaPacific IAP Congress
  • Place of Presentation: Taipei
  • Year and Date: 2011-05-24
• [Remarks]
  • URL: http://www.bri.niigata-u.ac.jp/