title: Increased Expression of 15-Hydroxyprostaglandin Dehydrogenase in Spinal Astrocytes During Disease Progression in a Model of Amyotrophic Lateral Sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive, and fatal neurodegenerative disease caused by selective loss of motor neurons. Both ALS model mice and patients with sporadic ALS have increased levels of prostaglandin E2 (PGE2). Furthermore, the protein levels of microsomal PGE synthase-1 and cyclooxygenase-2, which catalyze PGE2 biosynthesis, are significantly increased in the spinal cord of ALS model mice. However, it is unclear whether PGE2 metabolism in the spinal cord is altered. In the present study, we investigated the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in prostaglandin metabolism, in ALS model mice at three different disease stages. Western blotting revealed that the 15-PGDH level was significantly increased in the lumbar spinal cord at the symptomatic stage and end stage. Immunohistochemical staining demonstrated that 15-PGDH immunoreactivity was localized in glial fibrillary acidic protein (GFAP)-positive astrocytes at the end stage. In contrast, 15-PGDH immunoreactivity was not identified in NeuN-positive large cells showing the typical morphology of motor neurons in the anterior horn. Unlike 15-PGDH, the level of PGE2 in the spinal cord was increased only at the end stage. These results suggest that the significant increase of PGE2 at the end stage of ALS in this mouse model is attributable to an imbalance of the synthetic pathway and 15-PGDH-dependent scavenging system for PGE2, and that this drives the pathogenetic mechanism responsible for transition from the symptomatic stage.
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.|Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyagishi
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan. kosuge.yasuhiro@nihon-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kosuge
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takano
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Endo
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nango
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Somay
authors.initials: S
authors.lastname: Yamagata-Murayama
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Hirose
authors.affiliation: College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-8510, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Kano
authors.affiliation: School of Dentistry of Matsudo, Nihon University, 2-870-1 Sakaechonishi, Matsudo, Chiba, 271-8587, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ishige
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology*; D066151:Spinal Cord Ventral Horn / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation
chemical_list: D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone
keywords: 15-Hydroxyprostaglandin dehydrogenase; Amyotrophic lateral sclerosis; Astrocyte; Lumbar spinal cord; Prostaglandin E2