Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week.
Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week.
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DOI：
10.1016/j.jneuroim.2014.11.018
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发表时间：
2015-01-15
影响因子：
3.3
通讯作者：
Watters, Jyoti J.
中科院分区：
文献类型：
--
作者：
Nikodemova, Maria;Kimyon, Rebecca S.;De, Ishani;Small, Alissa L.;Collier, Lara S.;Watters, Jyoti J.
在出生后发育过程中，小胶质细胞是中枢神经系统固有的免疫细胞，对突触修剪、神经元凋亡和重塑起着至关重要的作用。在此期间，小胶质细胞经历了形态和表型的转变；然而，关于小胶质细胞的数量和密度在出生后中枢神经系统发育过程中是如何调节的，人们知之甚少。我们发现，在出生后14天内，小鼠大脑中的小胶质细胞数量在出生后14天开始增加，在出生后第三周开始下降，到6周时减少了50%；这些“成年”水平一直保持到至少9个月大。小胶质细胞CD11b水平升高，而CD45和ER-MP58水平在P10和成年期之间下降，这与成熟的小胶质细胞表型一致。我们的数据表明，小胶质细胞凋亡的增加和增殖能力的降低都是导致小胶质细胞数量发育减少的原因。我们发现小胶质细胞数量的发育减少与脑内CD200、Cx3Cl1、M-CSF或IL-34的mRNA水平之间没有相关性。我们在出生后第三周检测了促进小胶质细胞增殖和存活的关键生长因子M-CSF过表达对防止小胶质细胞丢失的能力。在所有被测试的年龄段，在星形胶质细胞中过度表达M-CSF的小鼠的小胶质细胞数量都较多。然而，小胶质细胞数量的发育性下降仍然存在，这表明慢性升高的M-CSF无法克服小胶质细胞数量的发育性减少。尽管在发育过程中调节小胶质细胞数量和密度的因子(S)的同一性仍有待确定，但小胶质细胞可能对“成熟”信号做出反应，因为小胶质细胞数量的减少与中枢神经系统的成熟相一致。
During postnatal development, microglia, CNS resident innate immune cells, are essential for synaptic pruning, neuronal apoptosis and remodeling. During this period microglia undergo morphological and phenotypic transformations; however, little is known about how microglial number and density is regulated during postnatal CNS development. We found that after an initial increase during the first 14 postnatal days, microglial numbers in mouse brain began declining in the third postnatal week and were reduced by 50% by 6 weeks of age; these “adult” levels were maintained until at least 9 months of age. Microglial CD11b levels increased, whereas CD45 and ER-MP58 declined between P10 and adulthood, consistent with a maturing microglial phenotype. Our data indicate that both increased microglial apoptosis and a decreased proliferative capacity contribute to the developmental reduction in microglial numbers. We found no correlation between developmental reductions in microglial numbers and brain mRNA levels of Cd200, Cx3Cl1, M-Csf or Il-34. We tested the ability of M-Csf-overexpression, a key growth factor promoting microglial proliferation and survival, to prevent microglial loss in the third postnatal week. Mice overexpressing M-Csf in astrocytes had higher numbers of microglia at all ages tested. However, the developmental decline in microglial numbers still occurred, suggesting that chronically elevated M-CSF is unable to overcome the developmental decrease in microglial numbers. Whereas the identity of the factor(s) regulating microglial number and density during development remains to be determined, it is likely that microglia respond to a “maturation” signal since the reduction in microglial numbers coincides with CNS maturation.
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