Comparing the effects of microgravity and amyotrophic lateral sclerosis on mouse dorsal root ganglia

Frontiers in Space Technologies

Space Technologies

Takashi Kudo¹  Satoru Takahashi¹  Mamoru Uemura²  Masafumi Muratani³  Mutsumi Matsukawa⁴  Shin Aizawa⁴  Masaaki Yoshikawa⁵  Hideki Oshima⁶  Dai Shiba⁷  Masaki Shirakawa⁷  Haiyan Li⁸  Chihiro Ishikawa⁸  Takashi Shiga⁹ 

[1] Department of Anatomy and Embryology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan;Department of Anatomy, Osaka Dental University, Osaka, Japan;Department of Genome Biology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan;Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan;Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan;Department of Anatomy, Osaka Dental University, Osaka, Japan;Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan;JEM Utilization Center, Human Spaceflight Technology Directorate, Japan Aerospace Exploration Agency (JAXA), Ibaraki, Japan;Laboratory of Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan;Laboratory of Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan;Department of Neurobiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan;

关键词: microgravity;    amyotrophic lateral sclerosis;    dorsal root ganglion neuron;    proprioceptor;    cutaneous low-threshold mechanoreceptor;    nociceptor;    satellite glial cell;    Imoonglia;   

DOI  :  10.3389/frspt.2023.1162268

 received in 2023-02-21, accepted in 2023-06-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Microgravity (MG) exposure causes motor deficits and decreased neuronal activity, effects that resemble the ones observed in motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Several recent studies have shown that exposure to MG and ALS also impacts the sensory systems. Yet, the role of sensory impairment in this degenerative process of exposure to MG and ALS remains unknown. In this study, we aimed at elucidating how the sensory system is affected by exposure to MG and ALS.Methods: To this end, we compared gene expression in the mouse lumbar dorsal root ganglia (DRG) of MG-exposed animals with that of control animals that remained under artificial gravity conditions. We then investigated the effects of the human superoxide dismutase 1 (SOD1) G93A mutation in a mouse model of ALS (SOD1G93A mice) on gene expression in the DRG.Results: The overlap of genes with negatively correlated expression was greater than those with positively correlated expression between the DRG of MG-exposed and SOD1G93A mice. Additionally, genes related to Imoonglia (characteristics of both immune and glial cells) and macrophage increased in response to MG exposure, while satellite glial cell genes were expressed in response to SOD1 mutation. Next, we examined genes related to sensory neuron subtypes in the DRG. We found altered gene expression in genes related to proprioceptive and mechanoreceptive neurons in the DRG of MG-exposed and SOD1G93A mice. Remarkably, the expression of Atf3 and genes related to nociceptive neurons in the DRG of SOD1G93A mice at postnatal day (P) 120 was considerably altered, whereas MG-exposed and SOD1G93A mice at P30 presented little changes.Discussion: These results indicate that exposure to MG and ALS affect gene expression in genes related to neurons and non-neuronal cells in the DRG, with significant differences between the effects of MG and the SOD1 mutation. Elucidation of the impact of exposure to MG and ALS pathogenesis in the DRG, including identification of the molecular pathways that regulate DRG dysfunction, will help better understand the differences in vulnerability and the triggering processes of impaired motor function associated with MG and ALS.

【 授权许可】

Unknown   
Copyright © 2023 Yoshikawa, Matsukawa, Oshima, Ishikawa, Li, Kudo, Shiba, Shirakawa, Muratani, Takahashi, Uemura, Aizawa and Shiga.