P2Y₁₂ receptor is expressed on human microglia under physiological conditions throughout development and is sensitive to neuroinflammatory diseases

详细信息    查看全文

• 作者：Alexander Mildner ; Hao Huang ; Josefine Radke ; Werner Stenzel and Josef Priller
• 刊名：Glia
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：65
• 期：2
• 页码：375-387
• 全文大小：1332K
• ISSN：1098-1136

文摘

Microglia are resident immune cells in the central nervous system (CNS), which are essential for immune defence and critically contribute to neuronal functions during homeostasis. Until now, little is known about microglia biology in humans in part due to the lack of microglia-specific markers. We therefore investigated the expression of the purinergic receptor P2Y₁₂ in human brain tissue. Compared to classical markers used to identify microglia such as Iba1, CD68 or MHCII, we found that P2Y₁₂ is expressed on parenchymal microglia but is absent from perivascular or meningeal macrophages. We further demonstrate that P2Y₁₂ expression is stable throughout human brain development, including fetal phases, and quantification of P2 on-construct="true" class="math-equation-construct">on-image="true" class="math-equation-image">on-mathml="true" class="math-equation-mathml" style="display:none">org/1998/Math/MathML">ow xmlns:w="http://www.wiley.com/namespaces/wiley" xmlns:wiley="http://www.wiley.com/namespaces/wiley/wiley" xmlns:cr="urn://wiley-online-library/content/render" xmlns="http://www.w3.org/1998/Math/MathML">ow>ormal">Yow>ow>12ow>ow>o>+o>ow>ow> microglia revealed that the density of human microglia is constant throughout lifetime. In contrast, CD68 expression increases during aging in cerebellar but not in cortical microglia, indicating regional heterogeneity. CNS pathologies such as Alzheimer's disease or multiple sclerosis—but not schizophrenia—result in decreased P2Y₁₂ immunoreactivity in plaque- or lesion-associated myeloid cells, whereas Iba1 expression remains detectable. Our results suggest that P2Y₁₂ is a useful marker for the identification of human microglia throughout the lifespan. Moreover, P2Y₁₂ expression might help to discriminate activated microglia and infiltrating myeloid cells from quiescent microglia in the human CNS. GLIA 2017;65:375–387