Thrash J Cameron, Torbett Bruce E, Carson Monica J
Division of Biomedical Sciences, Center for Glial-Neuronal Interactions, University of California Riverside, 900 University Ave, Riverside, CA, 92521, USA.
Neurochem Res. 2009 Jan;34(1):38-45. doi: 10.1007/s11064-008-9657-1. Epub 2008 Apr 11.
Trem2 is an orphan, DAP12 associated receptor constitutively expressed in vivo by subsets of microglia in the healthy adult murine CNS and in vitro by subsets of oligodendrocytes in neonatal mixed glial cultures. Loss of a functional Trem2 signaling pathway is the genetic cause of Nasu-Hakola disease. Whether the early onset cognitive dementia and myelin-pallor associated with this disorder are due to deficits in functional Trem2 signaling in microglia and/or oligodendrocytes is still being debated. Here, we find that Trem2/DAP12 expression is detected in embryonic day 14 CNS mRNA. Using dual immunohistochemistry/in situ hybridization, we find that both Trem2 and DAP12 expression always co-localized with markers of microglia/macrophages. However, Trem2/DAP12 positive microglia are found in very close apposition with CNP+ oligodendrocytes prior to myelination (post-natal day 1). In addition, CNS expression of TREM2 and DAP12 are not detected in PU.1KO which lack microglia and macrophages. Our data provide continuing support for Nasu-Hakola disease being identified as a cognitive disorder caused by a primary dysfunction of CNS microglia.
Trem2是一种孤儿受体，与DAP12相关，在健康成年小鼠中枢神经系统中由小胶质细胞亚群在体内组成性表达，在新生混合胶质细胞培养物中由少突胶质细胞亚群在体外组成性表达。功能性Trem2信号通路的缺失是纳苏-哈科拉病的遗传病因。与这种疾病相关的早发性认知性痴呆和髓鞘苍白是否归因于小胶质细胞和/或少突胶质细胞中功能性Trem2信号的缺陷仍在争论中。在这里，我们发现在胚胎第14天的中枢神经系统mRNA中检测到Trem2/DAP12表达。使用双重免疫组织化学/原位杂交，我们发现Trem2和DAP12表达总是与小胶质细胞/巨噬细胞的标志物共定位。然而，在髓鞘形成之前（出生后第1天），发现Trem2/DAP12阳性小胶质细胞与CNP+少突胶质细胞非常紧密地相邻。此外，在缺乏小胶质细胞和巨噬细胞的PU.1KO中未检测到TREM2和DAP12的中枢神经系统表达。我们的数据继续支持将纳苏-哈科拉病确定为由中枢神经系统小胶质细胞原发性功能障碍引起认知障碍。
