title: Reductions of docosahexaenoic acid-containing phosphatidylcholine levels in the anterior horn of an ALS mouse model.
abstract: In this study, we analyzed the spatiotemporal alterations of phospholipid composition in the spinal cord of an amyotrophic lateral sclerosis (ALS) mouse model (G93A-mutated human superoxide dismutase 1 transgenic mice [SOD1(G93A) mice]) using imaging mass spectrometry (IMS), a powerful method to visualize spatial distributions of various types of molecules in situ. Using this technique, we deciphered the phospholipid distribution in the pre-symptomatic stage, early stage after disease onset, and terminal stages of disease in female SOD1(G93A) mouse spinal cords. These experiments revealed a significant decrease in levels of docosahexaenoic acid (DHA)-containing phosphatidylcholines (PCs), such as PC (diacyl-16:0/22:6), PC (diacyl-18:0/22:6), and PC (diacyl-18:1/22:6) in the L5 anterior horns of terminal stage (22-week-old) SOD1(G93A) mice. The reduction in PC (diacyl-16:0/22:6) level could be reflecting the loss of motor neurons themselves in the anterior horn of the spinal cord in ALS model mice. In contrast, other PCs, such as PC (diacyl-16:0/16:0), were observed specifically in the L5 dorsal horn gray matter, and their levels did not vary between ALS model mice and controls. Thus, our study showed a significant decrease in DHA-containing PCs, but not other PCs, in the terminal stage of ALS in model mice, which is likely to be a reflection of neuronal loss in the anterior horns of the spinal cords. Given its enrichment in dorsal sensory regions, the preservation of PC (diacyl-16:0/16:0) may be the result of spinal sensory neurons being unaffected in ALS. Taken together, these findings suggest that ALS spinal cords show significant alterations in PC metabolism only at the terminal stage of the disease, and that these changes are confined to specific anatomical regions and cell types.
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan; Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Arima
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Omura
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan; Faculty of Health Science, Hokkaido University Graduate School of Medicine, Japan, Kita 12, Nishi 5, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayasaka
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Masaki
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hanada
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Banno
authors.affiliation: Department of Orthopedics, Nagoya University Graduate School of Medicine, Japan, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Japan, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Japan, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kadomatsu
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuyama
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan; Department of Anatomy, The University of Hong Kong, Pok Fu Lam, 999077, Hong Kong; JST, ERATO, Sato project, Tokyo 160-8582, Japan. Electronic address: setou@hama-med.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Setou
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010713:Phosphatidylcholines / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013116:Spinal Cord / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D010713:Phosphatidylcholines; D004281:Docosahexaenoic Acids; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: ALS; DHA; anterior horn; imaging mass spectrometry; neuronal loss; phosphatidylcholine