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
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
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DOI：
10.1097/01.jnen.0000240472.43038.27
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发表时间：
2007-06-01
影响因子：
3.2
通讯作者：
Taniike, Masako
中科院分区：
文献类型：
--
作者：
Mohri, Ikuko;Kadoyama, Kelichi;Taniike, Masako
前列腺素（PG）D-2是在活化的小胶质细胞中通过Hernatopoictic PGD合酶（HPGDS）的作用产生的，并且在神经炎症中起重要作用。由于神经炎症加速阿尔茨海默病（AD）进展的事实已被证明，因此我们研究了PGD（2）是否也参与AD的病理学。在这里，我们报告说，PGD（2）（DP 1）的受体的mRNA的水平增加，在AD脑与非AD脑的水平相比。免疫细胞化学分析显示HPGDS表达定位于老年斑周围的小胶质细胞。原位杂交研究表明，DP 1 mRNA特异性定位于小胶质细胞和反应性星形胶质细胞内的老年斑AD脑。在Tg 2576小鼠脑中，AD模型中，HPGDS和D（P）1蛋白主要定位于斑块中的小胶质细胞和星形胶质细胞中，并且其mRNA水平与淀粉样β蛋白沉积平行增加。这些结果表明，PGD（2）可能是AD脑中斑块相关炎症的介导者，并可能解释AD患者对非甾体抗炎药良好反应的药理学机制。
Prostaglandin (PG) D-2 is produced in activated microglia by the action of hernatopoictic 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 PGD(2) is also involved in the pathology of AD. Here, we report that the level of the mRNA of the receptor for PGD(2) (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 D(P)1 proteins were mainly localized immunocytochemically in microglia and astrocytes in the plaques, and the levels of their mRNAs increased in parallel with amyloid beta deposition. These results indicate that PGD(2) 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.