Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain.
Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain.
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DOI：
10.1038/s41467-020-19861-z
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发表时间：
2020-11-30
影响因子：
16.6
通讯作者：
Layé S
中科院分区：
文献类型：
--
作者：
Madore C;Leyrolle Q;Morel L;Rossitto M;Greenhalgh AD;Delpech JC;Martinat M;Bosch-Bouju C;Bourel J;Rani B;Lacabanne C;Thomazeau A;Hopperton KE;Beccari S;Sere A;Aubert A;De Smedt-Peyrusse V;Lecours C;Bisht K;Fourgeaud L;Gregoire S;Bretillon L;Acar N;Grant NJ;Badaut J;Gressens P;Sierra A;Butovsky O;Tremblay ME;Bazinet RP;Joffre C;Nadjar A;Layé S
Omega-3脂肪酸（n-3 PUFAs）是大脑功能成熟所必需的。在发达国家和发展中国家，饮食习惯的西化伴随着饮食中n-3 PUFAs摄入量的逐渐减少。母体n-3 PUFAs摄入量过低与人类神经发育疾病有关。然而，n-3 PUFAs缺乏介导的影响中枢神经系统发育的机制尚不清楚。活跃的小胶质细胞吞噬突触调节大脑发育。突触修剪受损与几种神经发育障碍有关。在这里，我们确定了低母体n-3 PUFA摄入量对小鼠海马发育有害影响的分子机制。我们的研究结果表明，母体饮食中n-3 PUFA缺乏增加了啮齿动物发育中的海马突触元件的小胶质细胞介导的吞噬，部分是通过激活12/15-脂氧合酶(LOX)/12-HETE信号，改变神经元形态并影响后代的认知表现。这些发现为母体n-3 PUFAs饮食缺乏引起的神经发育缺陷提供了机制见解。孕期脂肪酸摄入改变与神经发育障碍有关。在这里，作者表明母体omega-3脂肪酸缺乏导致小胶质细胞介导的突触元件吞噬改变，从而导致小鼠后代认知功能受损。
Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency. Altered fatty acid intake during pregnancy is associated with neurodevelopmental disorders. Here, the authors show that maternal omega-3 fatty acids deficiency results in altered microglia-mediated phagocytosis of synaptic elements leading to impaired cognitive functions in the offspring in mice.
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影响因子：
6.1
作者：
Diaz-Aparicio I;Beccari S;Abiega O;Sierra A
通讯作者：
Sierra A
影响因子：
2.5
作者：
Almaas, Astrid Nylander;Tamnes, Christian K.;Drevon, Christian A.
通讯作者：
Drevon, Christian A.
影响因子：
32.4
作者：
Filipello, Fabia;Morini, Raffaella;Matteoli, Michela
通讯作者：
Matteoli, Michela
影响因子：
34.7
作者：
Brown, Guy C.;Neher, Jonas J.
通讯作者：
Neher, Jonas J.
影响因子：
4.7
作者：
De Smedt-Peyrusse, Veronique;Sargueil, Francoise;Laye, Sophie
通讯作者：
Laye, Sophie