Mohri Ikuko, Eguchi Naomi, Suzuki Kinuko, Urade Yoshihiro, Taniike Masako
Department of Developmental Medicine (Pediatrics), Osaka University Graduate School of Medicine, Osaka, Japan.
Glia. 2003 May;42(3):263-74. doi: 10.1002/glia.10183.
Hematopoietic prostaglandin D synthase (HPGDS) is a PGD(2)-synthesizing enzyme and is expressed in antigen-presenting cells, mast cells, and other immunocompetent cells. We here report the HPGDS expression in microglia and the migration pathway of microglia in the developing mouse brain as detected by HPGDS immunohistochemistry. Expression of HPGDS mRNA peaked at postnatal day (PND) 10, decreased gradually thereafter, and reached a plateau at PND 20. The mRNAs for target molecules of PGD(2), i.e., DP receptor (DPR) and CRTH2 receptor, showed developmental profiles overlapped to that of HPGDS. Most of the HPGDS(+) cells at PND 10 had morphological characteristics of ameboid microglia and gave positive immunostaining with microglia-specific markers such as RCA-1, F4/80, or ER-MP12. These specific markers became less detectable later on, but HPGDS was still expressed even in resting microglia. Thus, HPGDS is a useful marker for investigation of microglial development. Spaciotemporal evaluation of microglial development and migration with HPGDS immunostaining revealed the following three major possible migration pathways of microglia in the postnatal brain: from the lateral ventricle via subventricular zones to brain parenchyma; from the leptomeninges around the cerebellopontine angle to the cerebellar white matter; and from the overlying leptomeninges to the hippocampus, basal forebrain, and brainstem.
造血前列腺素D合成酶(HPGDS)是一种合成前列腺素D2(PGD2)的酶,在抗原呈递细胞、肥大细胞和其他免疫活性细胞中表达。我们在此报告通过HPGDS免疫组织化学检测到的小胶质细胞中HPGDS的表达以及发育中小鼠大脑中小胶质细胞的迁移途径。HPGDS mRNA的表达在出生后第10天(PND 10)达到峰值,此后逐渐下降,并在PND 20达到稳定水平。PGD2靶分子的mRNA,即DP受体(DPR)和CRTH2受体,显示出与HPGDS重叠的发育模式。PND 10时大多数HPGDS阳性细胞具有阿米巴样小胶质细胞的形态特征,并用小胶质细胞特异性标记物如RCA-1、F4/80或ER-MP12进行免疫染色呈阳性。这些特异性标记物后来变得难以检测到,但HPGDS即使在静止的小胶质细胞中仍有表达。因此,HPGDS是研究小胶质细胞发育的有用标记物。用HPGDS免疫染色对小胶质细胞发育和迁移进行时空评估,揭示了出生后大脑中小胶质细胞的以下三种主要可能迁移途径:从侧脑室经脑室下区至脑实质;从小脑桥脑角周围的软脑膜至小脑白质;以及从上方的软脑膜至海马、基底前脑和脑干。