{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:21:54Z","timestamp":1791141714702,"version":"4.1.0"},"reference-count":62,"publisher":"Society for Neuroscience","issue":"16","license":[{"start":{"date-parts":[[2006,10,19]],"date-time":"2006-10-19T00:00:00Z","timestamp":1161216000000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2006,4,19]]},"abstract":"<jats:p>Prostaglandin (PG) D<jats:sub>2<\/jats:sub>is well known as a mediator of inflammation. Hematopoietic PGD synthase (HPGDS) is responsible for the production of PGD<jats:sub>2<\/jats:sub>involved in inflammatory responses. Microglial activation and astrogliosis are commonly observed during neuroinflammation, including that which occurs during demyelination. Using the genetic demyelination mouse<jats:italic>twitcher<\/jats:italic>, a model of human Krabbe\u2019s disease, we discovered that activated microglia expressed HPGDS and activated astrocytes expressed the DP<jats:sub>1<\/jats:sub>receptor for PGD<jats:sub>2<\/jats:sub>in the brain of these mice. Cultured microglia actively produced PGD<jats:sub>2<\/jats:sub>by the action of HPGDS. Cultured astrocytes expressed two types of PGD<jats:sub>2<\/jats:sub>receptor, DP<jats:sub>1<\/jats:sub>and DP<jats:sub>2<\/jats:sub>, and showed enhanced GFAP production after stimulation of either receptor with its respective agonist. These results suggest that PGD<jats:sub>2<\/jats:sub>plays an important role in microglia\/astrocyte interaction. We demonstrated that the blockade of the HPGDS\/PGD<jats:sub>2<\/jats:sub>\/DP signaling pathway using HPGDS- or DP<jats:sub>1<\/jats:sub>-null<jats:italic>twitcher<\/jats:italic>mice, and<jats:italic>twitcher<\/jats:italic>mice treated with an HPGDS inhibitor, HQL-79 (4-benzhydryloxy-1-[3-(1<jats:italic>H<\/jats:italic>-tetrazol-5-yl)-propyl]piperidine), resulted in remarkable suppression of astrogliosis and demyelination, as well as a reduction in twitching and spasticity. Furthermore, we found that the degree of oligodendroglial apoptosis was also reduced in HPGDS-null and HQL-79-treated<jats:italic>twitcher<\/jats:italic>mice. These results suggest that PGD<jats:sub>2<\/jats:sub>is the key neuroinflammatory molecule that heightens the pathological response to demyelination in<jats:italic>twitcher<\/jats:italic>mice.<\/jats:p>","DOI":"10.1523\/jneurosci.4531-05.2006","type":"journal-article","created":{"date-parts":[[2006,4,19]],"date-time":"2006-04-19T18:41:19Z","timestamp":1145472079000},"page":"4383-4393","source":"Crossref","is-referenced-by-count":180,"title":["Prostaglandin D<sub>2<\/sub>-Mediated Microglia\/Astrocyte Interaction Enhances Astrogliosis and Demyelination in<i>twitcher<\/i>"],"prefix":"10.1523","volume":"26","author":[{"given":"Ikuko","family":"Mohri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Taniike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Kanekiyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Aritake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Inui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Fukumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Kushi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Sasai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Kanaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Ozono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuh","family":"Narumiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinuko","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Urade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2006,4,19]]},"reference":[{"key":"2023041303175304000_26.16.4383.1","doi-asserted-by":"crossref","unstructured":"Aritake K, Kado Y, Inoue T, Miyano M, Urade Y (2006) Structural and functional characterization of HQL-79, an orally active, selective inhibitor for human hematopoietic prostaglandin D synthase. 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