N-3 PUFA Deficiency Affects the Ultrastructural Organization and Density of White Matter Microglia in the Developing Brain of Male Mice.

N-3 PUFA Deficiency Affects the Ultrastructural Organization and Density of White Matter Microglia in the Developing Brain of Male Mice.
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DOI:
10.3389/fncel.2022.802411
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发表时间:
2022
影响因子:
5.3
通讯作者:
Nadjar A
Nadjar A
中科院分区:
医学2区
文献类型:
--
作者:
Decoeur F;Picard K;St-Pierre MK;Greenhalgh AD;Delpech JC;Sere A;Layé S;Tremblay ME;Nadjar A

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在过去的世纪,西方化的饮食习惯已导致饮食中的n-3多不饱和脂肪酸(n-3 PUFA)的摄入量急剧减少。特别是,在整个妊娠期和哺乳期,母亲摄入n-3 PUFA量低,导致脑髓鞘形成缺陷。小胶质细胞因其对神经发育过程如髓鞘形成的关键贡献而被公认。这些细胞在出生后的第一周侵入白色物质,在那里它们参与少突胶质细胞的成熟和髓鞘的产生。因此,我们研究了是否改变白色物质小胶质细胞伴随着髓鞘形成缺陷中观察到的n-3 PUFA缺陷动物的大脑。宏观成像分析显示,母体n-3 PUFA缺乏降低了出生后第10天左右白色物质小胶质细胞的密度。显微电子显微镜分析还显示小胶质细胞超微结构的改变,小胶质细胞和髓鞘之间的接触数量减少,细胞体中髓鞘碎片的数量减少。白色小胶质细胞在围产期n-3 PUFA缺乏时进一步显示线粒体丰度和网络面积增加。总体而言,我们的数据表明,母体n-3 PUFA缺乏改变了小胶质细胞的结构和功能,位于白色物质的幼崽在生命早期,这可能是关键,以了解髓鞘形成缺陷在神经发育过程中。
Over the last century, westernization of dietary habits has led to a dramatic reduction in dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs). In particular, low maternal intake of n-3 PUFAs throughout gestation and lactation causes defects in brain myelination. Microglia are recognized for their critical contribution to neurodevelopmental processes, such as myelination. These cells invade the white matter in the first weeks of the post-natal period, where they participate in oligodendrocyte maturation and myelin production. Therefore, we investigated whether an alteration of white matter microglia accompanies the myelination deficits observed in the brain of n-3 PUFA-deficient animals. Macroscopic imaging analysis shows that maternal n-3 PUFA deficiency decreases the density of white matter microglia around post-natal day 10. Microscopic electron microscopy analyses also revealed alterations of microglial ultrastructure, a decrease in the number of contacts between microglia and myelin sheet, and a decreased amount of myelin debris in their cell body. White matter microglia further displayed increased mitochondrial abundance and network area under perinatal n-3 PUFA deficiency. Overall, our data suggest that maternal n-3 PUFA deficiency alters the structure and function of microglial cells located in the white matter of pups early in life, and this could be the key to understand myelination deficits during neurodevelopment.
DOI: 10.1016/j.bbih.2021.100281
发表时间: 2021-08
期刊: Brain, behavior, & immunity - health
影响因子: --
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