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ポリグルタミン病、ALS、脊髄小脳変性症、その他の神経変性疾患 2
Polyglutamine Diseases, ALS, SCD, Other Neurodegenerative Disorder 2

開催日 2014/9/11
時間 10:00 - 11:00
会場 Room I(311+312)
Chairperson(s) 柳 茂 / Shigeru Yanagi (東京薬科大学 生命科学部 分子性化学研究室 / Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Japan)
三澤 日出巳 / Hidemi Misawa (慶應義塾大学薬学部 薬理学 / Department of Pharmacology, Faculty of Pharmacy, Keio University, Japan)

Osteopontin Serves as a Marker for Discriminating Alpha Motor Neuron Subtypes in the Mouse Spinal Cord

  • O1-I-2-1
  • 森﨑 祐太 / Yuta Morisaki:1 坪田 充司 / Atsushi Tsubota:1 森脇 康博 / Yasuhiro Moriwaki:1 奥田 隆志 / Takashi Okuda:1 山中 宏二 / Koji Yamanaka:2 三澤 日出巳 / Hidemi Misawa:1 
  • 1:慶應大・薬・薬理 / Dept Pharmacol, Keio Univ. Fac. Pharm., Tokyo, Japan 2:名古屋大・環医研・病態神経科学 / Dept Neuroscience and Pathology, Research Institute of Environmental Medicine, Nagoya Univ., Aichi, Japan 

Selective vulnerability of specific neuronal systems is a pathological hallmark in neurodegenerative diseases (e.g., a subpopulation of motor neurons, MNs, is more vulnerable to death than other MNs in amyotrophic lateral sclerosis, ALS). MNs are divided into two types: alpha MNs, which innervate extrafusal muscle fibers, and gamma MNs, which innervate intrafusal muscle fibers. Alpha MNs are further classified into three subtypes: FF (fast-twitch-fatigable), FR (fast-twitch fatigue-resistant), and S (slow-twitch fatigue-resistant) MNs. The MN subtypes are defined by their physiological characteristics (e.g., excitability) and the type of innervating muscle fibers (I, IIA, IIB). However, little is known about the molecular differences among these subtypes. In this study, we tried to define the FF, FR, and S MNs by contrasting localization of two molecular markers, osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9). We have previously reported that OPN (which was originally discovered as a bone matrix protein, but later recognized as a multifunctional protein involved in tissue inflammation and remodeling) is selectively expressed in alpha MNs, but not in gamma MNs. Recently, Kaplan et al. (Neuron 81, 333-348, 2014) reported that MMP-9 is a marker for FF alpha MNs. We performed immunohistochemical analyses in the mouse spinal cord, by triple staining for OPN, MMP-9, and choline acetyltransferase (ChAT), and observed different staining levels between OPN and MMP-9 among ChAT-positive MNs. These were classified as OPN-high/MMP-9-low and OPN-low/MMP-9-high MNs. By using a retrograde labeling procedure, we confirmed that the OPN-high/MMP-9-low types were FR or S MNs and the OPN-low/MMP-9-high types were FF MNs. These markers will be useful in analyzing subtype-selective vulnerability of MNs in various mouse disease models (whose MNs are undergoing degeneration) and in analyzing phenotypic changes during functional compensation/remodeling of the motor units.

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