Prostaglandin D2-Mediated Microglia/Astrocyte Interaction Enhances Astrogliosis and Demyelination intwitcher

• DOI: 10.1523/jneurosci.4531-05.2006
• Publication Date: 2006-04-19T18:41:19Z
• Authors: Ikuko Mohri; Masako Taniike; Hidetoshi Taniguchi; Takahisa Kanekiyo; Kosuke Aritake; Takashi Inui; Noriko Fukumoto; Naomi Eguchi; Atsuko Kushi; Hitoshi Sasai; Yoshihide Kanaoka; Keiichi Ozono; Shuh Narumiya; Kinuko Suzuki; Yoshihiro Urade
• Keywords: Astrogliosis

Prostaglandin (PG) D 2 is well known as a mediator of inflammation. Hematopoietic PGD synthase (HPGDS) responsible for the production involved in inflammatory responses. Microglial activation and astrogliosis are commonly observed during neuroinflammation, including that which occurs demyelination. Using genetic demyelination mouse twitcher , model human Krabbe’s disease, we discovered activated microglia expressed HPGDS astrocytes DP 1 receptor brain these mice. Cultured actively produced by action HPGDS. two types receptor, showed enhanced GFAP after stimulation either with its respective agonist. These results suggest plays an important role microglia/astrocyte interaction. We demonstrated blockade HPGDS/PGD /DP signaling pathway using HPGDS- or -null mice, mice treated inhibitor, HQL-79 (4-benzhydryloxy-1-[3-(1 H -tetrazol-5-yl)-propyl]piperidine), resulted remarkable suppression demyelination, reduction twitching spasticity. Furthermore, found degree oligodendroglial apoptosis was also reduced HPGDS-null HQL-79-treated key neuroinflammatory molecule heightens pathological response to