title: Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice.
abstract: Multiple sclerosis is a chronic demyelinating disease of the central nervous system leading to progressive cognitive and motor dysfunction, which is characterized by neuroinflammation, demyelination, astrogliosis, loss of oligodendrocytes, and axonal pathologies. Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death. In this study, we investigated the effects of cPA on cuprizone-induced demyelination, which is a model of multiple sclerosis. Mice were fed a diet containing 0.2% cuprizone for 5 weeks, which induces severe demyelination, astrocyte and microglial activation, and motor dysfunction. Simultaneous administration of cPA effectively attenuated cuprizone-induced demyelination, glial activation, and motor dysfunction. These data indicate that cPA may be a useful treatment to reduce the extent of demyelination and the severity of motor dysfunction in multiple sclerosis. cPA is a potential lead compound in the development of drugs for the treatment of this devastating disease.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Endowed Research Division of Human Welfare Sciences, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Department of Liberal Arts, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Yamashina
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Sosuke
authors.initials: S
authors.lastname: Yagishita
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Awaji
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Endowed Research Division of Human Welfare Sciences, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Murakami-Murofushi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. Electronic address: keisukey@saitama-med.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D019957:Motor Skills Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010712:Phosphatidic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D010712:Phosphatidic Acids; C555818:cyclic phosphatidic acid 16:0; D003471:Cuprizone
keywords: Cuprizone (CPZ) (PubChem CID: 9723); Cyclic phosphatidic acid (cPA); Demyelination; Multiple sclerosis (MS)