Hematopoietic prostaglandin D synthase and DP1 receptor are selectively upregulated in microglia and astrocytes within senile plaques from human patients and in a mouse model of Alzheimer disease

Ikuko Mohri, Keiichi Kadoyama, Takahisa Kanekiyo, Yo Sato, Kuriko Kagitani-Shimono, Yuko Saito, Kinuko Suzuki, Takashi Kudo, Masatoshi Takeda, Yoshihiro Urade, Shigeo Murayama, Masako Taniike

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Prostaglandin (PG) D2 is produced in activated microglia by the action of hematopoietic PGD synthase (HPGDS) and plays important roles in neuroinflammation. Because the fact that neuroinflammation accelerates progression of Alzheimer disease (AD) has been documented, we investigated whether PGD2 is also involved in the pathology of AD. Here, we report that the level of the mRNA of the receptor for PGD2 (DP1) was increased in AD brains compared with the level in non-AD brains. Immunocytochemical analysis showed HPGDS expression to be localized in the microglia surrounding senile plaques. In situ hybridization studies revealed that DP1 mRNA was specifically localized in microglia and reactive astrocytes within senile plaques of AD brains. In the brain of Tg2576 mice, a model of AD, HPGDS and DP1 proteins were mainly localized immunocytochemically in microglia and astrocytes in the plaques, and the levels of their mRNAs increased in parallel with amyloid β deposition. These results indicate that PGD2 may act as a mediator of plaque-associated inflammation in AD brain and may explain the pharmacologic mechanisms underlying the favorable response of patients with AD to nonsteroidal anti-inflammatory drugs.

Original languageEnglish (US)
Pages (from-to)469-480
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number6
DOIs
StatePublished - Jun 2007

Keywords

  • Alzheimer disease
  • Amyloid β
  • Gliosis
  • Neuroinflammation
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Prostanoid
  • Tg2576 mouse

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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