Approach to axon degeneration of motor neurons using pre-symptomatic ALS model mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Nihon University
• Principal Investigator: YOSHIKAWA Masaaki 日本大学, 医学部, 助教 (50451696)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: RNA-seq / 神経血管ユニット / 毛細血管密度 / CGRP / Runx1

Outline of Final Research Achievements

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective degeneration of motor neurons. Although the major hallmark of ALS is the motor phenotype, alterations of non-neuronal cells were also reported in ALS model mice. However, the role of non-neuronal cell impairment for axonal degeneration in pre-symptomatic ALS is still unknown. To identify which cell types were more likely to be affected by the ALS pathogenesis, we analyzed differentially expressed genes (DEGs) with known cell-type markers. The changes of putative microglia, meningeal cells / Schwann cells, and oligodendrocyte precursor cells were identified as particular abnormalities in the ALS spinal cord at postnatal day 30 (denervated neuromuscular junction). In addition, alterations in the vasculature existed prior to neuromuscular junction denervation. These results suggest that various cell types contribute to axonal degeneration in pre-symptomatic ALS.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

ALSの進行を抑制する因子についてはこれまでに多くの報告がある。しかしながら、発症を遅らせる因子の報告はほとんどない。発症前の軸索変性に関わる分子メカニズムが解明できれば、発症を遅らせる研究への適用が可能であり、その意義は大きい。また、ALSの初期病変に関わる因子は、患者の発症前診断・早期治療につながる情報を得られるだけでなく、運動ニューロンの軸索変性を伴うサルコペニア（加齢に伴う筋減少）のような他疾患への応用・発展も期待される。