2006 Fiscal Year Final Research Report Summary
Prostaglandin D_2 is a key molecule for neuroinflammation in the demyelinating diseases
| Project/Area Number |
17591085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
TANIIKE Masako Osaka University, The Research center for Child Mental Development, Specially Appinted Professor, 子どものこころの分子統御機構研究センター, 特任教授(常勤) (30263289)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Norio Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (30314313)
WADA Kazuko Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (30294094)
ARAHORI Hitomi Osaka University Hospital, Perinatal center, Part-time Residfent, 医学部附属病院, 非常勤医員 (40379186)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Demyelination / Prostaglandin D2 / Neuroinflammation / Microglia / Astrocyte / Prostaglandin D synthase / Neuropathology / Apoptois |
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| Research Abstract |
Prostaglandin (PG) D2 is well known as an inflammatory mediator. The biological actions of PGD_2 are elicited through binding to DP_1 or DP_2 receptor. Hematopoi_etic PGD synthase (HPGDS) is responsible for the production of PGD_2,and is expressed in microglia in CNS. (Mohri et al.2003). The twitcher mouse (GALC^<twi/twi>) is an authentic animal model of human globoid cell leukodystrophy (Krabbe's disease) resulting from the deficiency of galactosylceramidase. In this model, the demyelination is caused by the apoptosis of oligodendrocytes (OLs) after postnatal day (PND) 30,and is always accompanied by the activation of microglia and gliosis throughout the brain. In this study, we found that HPGDS expression was progressively upregulated in activated microglia in the GALC^<twi/twi> brain. This upregulation was accompanied by the induction of the DP_1 receptor in hypertrophic astrocytes located close to HPGDS^+ microglia. Using primary culture of glial cells, we demonstrated that activated microglia produced large amount of PGD_2 by HPGDS and that astrocytes expressed both DP_1 and DP_2 receptors and were activated by PGD_2. Furthermore, by using HPGDS- or DP_1-deficient GALC^<twi/twi> mice and GALC^<twi/twi> mice treated with an HPGDS-inhibitor, we found that the blockade of the HPGDS/PGD_2/DP signaling pathway resulted in the suppression of gliosis and oligodendroglial apoptosis. This is the first example of a PGD_2-mediated microglia/astrocyte interaction in neuroinflammation.
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[Journal Article] Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury.2007
Author(s)
Taniguchi H, Mohri I, Okabe-Arahori H, Aritake K, Wada K, Kanekiyo T, Narumiya S, Nakayama M, Ozono K, Urade Y, Taniike M.
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Journal Title
J Neurosci 27
Pages: 4303-4312
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lipocalin-type prostaglandin D synthase/β-trace is a major amyloid β-chaperone in human cerebrospinal fluid2007
Author(s)
Kanekiyo T, Ban T, Aritake K, Huang Z-L, Qu W-M, Okazak I, Mohri I, Murayama S, Ozono K, Taniike M, Goto Y, Urade Y.
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Journal Title
Proc Natl Acad Sci U S A. 104
Pages: 6412-6417
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prostaglandin D_2-mediated Microglia/Astrocyte Interaction Enhances Astrogliosis and Demyelination in Twitcher.2006
Author(s)
Mohri I, Taniike M, Taniguchi H, Kanekiyo T, Aritake K, Inui T, Fukumoto N, Eguchi N, Kushi A, Sasai H, Kanaoka Y, Ozono K, Narumiya S, Suzuki K, Urade Y.
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Journal Title
J Neurosci. 26
Pages: 4383-93
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lipocalin-type Prostaglandin D Synthase Is Upregulated in Oligodendrocytes in Lysosomal Storage Diseases and Binds Gangliosides.2006
Author(s)
Mohri I, Taniike M, Okazaki I, Kagitani-Shimono K, Aritake K, Kanekiyo T, Yagi T, Takikita S, Kim H-S, Urade Y, Suzuki K.
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Journal Title
J Neurochem 97
Pages: 641-51
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hematopoietic Prostaglandin D synthase and DP1 receptor are selectively up-regulated in microglia and astrocytes within senile plaques from human patients and in a mouse model of Alzheimer's disease
Author(s)
Mohri I, Kadoyama K, Kanekiyo T, Sato Y, Kagitani-Shimono K, Saito Y, Suzuki K, Kudo T, Takeda M, Urade Y, Murayama S, Taniike M.
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Journal Title
J Neuropathol Exp Neurol. (in press)
Description
「研究成果報告書概要(欧文)」より
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