Microglial phospholipase D4 deficiency influences myelination during brain development.

Microglial phospholipase D4 deficiency influences myelination during brain development.
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DOI:
10.2183/pjab.92.237
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发表时间:
2016
期刊:
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子:
--
通讯作者:
Baba H
Baba H
中科院分区:
其他
文献类型:
--
作者:
Chiba T;Otani Y;Yamaguchi Y;Ishibashi T;Hayashi A;Tanaka KF;Yamazaki M;Sakimura K;Baba H

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磷脂酶D4(PLD 4)在出生后脑发育过程中短暂出现在白色物质中的活化小胶质细胞中表达。先前使用培养的小胶质细胞的敲除实验显示PLD 4参与吞噬和增殖。为了阐明PLD 4在体内的作用,产生PLD 4缺陷小鼠,并在出生后第5天(P5)和P7检查小脑,此时PLD 4在小胶质细胞中表达最高。野生型小胶质细胞在P5时表现出对小胶质细胞标记物CD68的强免疫反应性,而CD68信号在PLD 4缺陷型小胶质细胞中较弱,表明PLD 4的缺失影响小胶质细胞活化。在P5和P7,抗髓鞘碱性蛋白(MBP)抗体的免疫染色表明,轻度但显着的延迟髓鞘在PLD 4缺陷小脑。在P7时胼胝体也观察到类似的变化。然而,这种差异在P10不明显,表明小胶质细胞PLD 4缺陷主要影响早期髓鞘形成阶段。因此,小胶质细胞可能在发育过程中通过PLD 4相关机制在髓鞘形成中发挥短暂作用。
Phospholipase D4 (PLD4) is expressed in activated microglia that transiently appear in white matter during postnatal brain development. Previous knockdown experiments using cultured microglia showed PLD4 involvement in phagocytosis and proliferation. To elucidate the role of PLD4 in vivo, PLD4-deficient mice were generated and the cerebella were examined at postnatal day 5 (P5) and P7, when PLD4 expression is highest in microglia. Wild type microglia showed strong immunoreactivity for microglial marker CD68 at P5, whereas CD68 signals were weak in PLD4-deficient microglia, suggesting that loss of PLD4 affects microglial activation. At P5 and P7, immunostaining for anti-myelin basic protein (MBP) antibody indicated a mild but significant delay in myelination in PLD4-deficient cerebellum. Similar change was also observed in the corpus callosum at P7. However, this difference was not apparent at P10, suggesting that microglial PLD4-deficiency primarily influences the early myelination stage. Thus, microglia may have a transient role in myelination via a PLD4-related mechanism during development.
发育中的大鼠小脑中小胶质细胞的形态和吞噬性。
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