Amyotrophic lateral sclerosis : on the decreased transcription activity of ribosomal RNA gene and cell degeneration

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14580735
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: OYANAGI Kiyomitsu Tokyo Met.Org.Med.Res., Tokyo Met.Inst.Neurosci., Director, 東京都神経科学総合研究所, 参事研究員 (00134958)
• Co-Investigator(Kenkyū-buntansha): KANDA Naotoshi Tokyo Univ.of Agricul. & Tech., Professor, 農学部, 教授 (40075429) ; WATABE Kazuhiko Tokyo Met.Org.Med.Res., Tokyo Met.Inst.Neurosci., Scientist, 副参事研究員 (30240477) ; MISAWA Hidemi Tokyo Met.Org.Med.Res., Tokyo Met.Inst.Neurosci., Scientist, 主任研究員 (80219617)
• Project Period (FY): 2002 – 2004
• Keywords: Amyotrophic lateral sclerosis / ALS / Spinal cord / Anterior horn cell / Ribosome / Rough endoplasmic reticulum / Protein synthesis / Protein infolding

Research Abstract

Morphological changes of the protein synthesizing system including rough ER, molecular chaperon and Golgi apparatus, and transcription activity of ribosomal (r) RNA gene in the anterior horn cells of the patients with amyotrophic lateral sclerosis (ALS) were examined. The present research elucidated that the activity of the transcription of rRNA gene reduced very quickly after insults on the motor neurons, which induced decrease of cytoplasmic rRNA. Localization of molecular chaperon, KDEL, changed earlier than the fragmentation of the Golgi apparatus and decrease of Nissl substance in the anterior horn cells of the patients with ALS. The cisterns of the rER of the anterior horn cells of ALS were dilated irregularly, and the number of the attached ribosomes on the cistern decreased. Thus the protein synthesizing system in the anterior horn cells in ALS patients degenerated from upper stream to downstream.

Research Products

• [Journal Article] Oxidized Galectin-1 advances the functional recovery after peripheral nerve injury (2005)
  • Author(s): Kadoya T, et al.
  • Journal Title: Neurosci. Lett. 380 Pages: 284-288
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Oxidized Galectin-1 advances the functional recovery after peripheral nerve injury. (2005)
  • Author(s): Kadoya T, Oyanaai K, Kawakami E, Hasegawa M, Inagaki Y, Sohma Y, Horie H.
  • Journal Title: Neurosci.Lett. 380 Pages: 284-288
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Synthesis, localization and externalization of galectin-1 in mature dorsal root ganglion neurons and Schwann cells (2004)
  • Author(s): Sango K, et al.
  • Journal Title: Eur J Neurosci 19 Pages: 55-64
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ultrastructural localization of high-affinity choline transporter in the rat neuromuscular junction : Enrichment on synaptic vesicles (2004)
  • Author(s): Nakata K, et al.
  • Journal Title: Synapse 53 Pages: 53-56
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Calcium-permeable AMPA receptors promote misfolding of mutant S0D1 protein and development of amyotrophic lateral sclerosis in a transgenic mouse model (2004)
  • Author(s): Tateno M, et al.
  • Journal Title: Hum. Mol. Genet. 13 Pages: 2183-2196
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distinctive expression of midkine in the repair period of rat brain during neurogenesis : Immunohistochemical and immunoelectron microscopic observations (2004)
  • Author(s): Kikuchi-Horie, K., Kawakami, E., Kamata, M., Wada, M., Hu, JG., Nakagawa, H., Ohara, K., Watabe, K., Oyanagi, K.
  • Journal Title: J Neurosci Res 75 Pages: 678-687
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ultrastructural localization of high-affinity choline transporter in the rat neuromuscular junction : Enrichment on synaptic vesicles. (2004)
  • Author(s): Nakata, K., Okuda, T., Misawa, H.
  • Journal Title: Synapse 53 Pages: 53-56
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis : 102 autopsy cases examined between 1962 and 2000 (2003)
  • Author(s): Piao, Y.S., Wakabayashi, K., Kakita, A., Yamada, M., Hayashi, S., Morita, T., Ikuta, F., Oyanagi, K., Takahashi, H.
  • Journal Title: Brain Pathol 12 Pages: 10-22
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pathological involvement of the motor neuron system and hippocampal formation in motor neuron disease-inclusion dementia (2003)
  • Author(s): Toyoshima, Y., Piao, Y.-S., Tan, C.-H., Morita, M., Tanaka, M., Oyanagi, K., Okamoto, K., Takahashi, H.
  • Journal Title: Acta Neuropathologica 106 Pages: 50-56
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Topical instillation of ciliary neurotrophic factor inhibits retinal degeneration in streptozotocin-induced diabetic rats (2003)
  • Author(s): Aizu, Y., Katayama, H., Takahama, S., Hu, J.-G., Nakagawa, H., Oyanagi, K.
  • Journal Title: NeuroReport 14 Pages: 2067-2071
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adenoviral GDNF gene transfer prevents motoneuron loss in the nucleus ambiguus (2003)
  • Author(s): Saito, K., Shiotani, A., Watabe, K., Moro, K., Fukuda, H., Ogawa, K.
  • Journal Title: Brain Res 962 Pages: 61-67
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adenoviral gene transfer of GDNF, BDNF and TGFB2, but not CNTF, cardiotrophin-1 or IGFI, protects injured adult motoneurons after facial nerve avulsion. (2003)
  • Author(s): Sakamoto, T., Kawazoe, Y., Shen, JS., Takeda, Y., Arakawa, Y., Ogawa, J., Oyanagi, K., Ohashi, T., Watanabe, K., Inoue, K., Eto, Y., Watabe, K
  • Journal Title: J Neurosci Res 72 Pages: 54-64
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Oral administration of a neuroprotective compound T-588 prevents motoneuron degeneration after facial nerve avulsion in adult rats (2003)
  • Author(s): Ikeda, K., Sakamoto, T., Kawazoe, Y., Marubuchi, S., Nakagawa, M., Ono, S., Terashima, N., Kinoshita, M., Iwasaki, Y., Watabe, K.
  • Journal Title: Amyotroph Lateral Scler Other Motor Neuron Disord 4 Pages: 74-80
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Growth inhibitory factor prevents degeneration of injured adult rat motoneurons (2003)
  • Author(s): Sakamoto, T., Kawazoe, Y., Uchida, Y., Hozumi, I., Inuzuka, T., Watabe, K.
  • Journal Title: Neuroreport 14 Pages: 2147-2151
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] VAChT-Cre.Fast and VAChT-Cre.Slow : Postnatal Expression of Cre Recombinase in Somatomotor Neurons With Different Onset (2003)
  • Author(s): Misawa, H., Nakata, K., Toda, K., Matsuura, J., Oda, Y., Inoue, H., Tateno, M., Takahashi, R.
  • Journal Title: genesis 37 Pages: 44-50
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The crucial role of caspase-9 in the disease progression of a transgenic ALS mouse model (2003)
  • Author(s): Inoue, H., Tsukita, K., Iwasato, T., Suzuki, Y., Tomioka, M., Tateno, M., Nagao, M., Kawata, A., Saido, T.C., Miura, M., Misawa, H., Itohara, S., Takahashi, R.
  • Journal Title: EMBO J 22 Pages: 6665-6674
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn
  • Author(s): Anamizu Y, et al.
  • Journal Title: Acta Neuropathol (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The nature of the parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam and magnesium deficiency
  • Author(s): Oyanagi K
  • Journal Title: Parkinsonism Rel. Dis. (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Amyotrophic lateral sclerosis : On the origin on the degenerated fibers in the white matter of the spinal cord
  • Author(s): Oyanagi K, Yamazaki M, Kawakami E, Morita T, Makifuchi T, Takahashi H.
  • Journal Title: Amyotrophic lateral sclerosis : New Research, Nova Science Publishers (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn
  • Author(s): Anamizu Y, Kawaguchi H, Seichi A, Yamaguchi S, Kawakami E, Kanda N, Matsubara S, Kuro-o M, Nabeshima Y, Nakamura K, Oyanagi K.
  • Journal Title: Acta Neuropathol. (In press)
  • Description: 「研究成果報告書概要(欧文)」より