Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects.
Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects.
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DOI：
10.1038/mp.2016.103
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发表时间：
2017-11
影响因子：
11
通讯作者：
Yoon SY
中科院分区：
文献类型：
--
作者：
Kim HJ;Cho MH;Shim WH;Kim JK;Jeon EY;Kim DH;Yoon SY
自闭症谱系障碍（ASD）是由各种遗传和环境因素引起的神经发育障碍，导致突触异常。ASD的发展被认为涉及小胶质细胞，其在发育过程中的突触细化中发挥作用。自噬和相关通路也被认为参与了ASD。然而，小胶质细胞自噬在突触和ASD中的确切作用尚不清楚。在这里，我们表明，小胶质细胞自噬参与突触细化和神经行为调节。我们发现，从骨髓细胞特异性溶菌酶M-Cre小鼠中删除atg 7（对自噬至关重要）导致了社会行为缺陷和重复行为，这是ASD的特征。这些小鼠的树突棘和突触标记物也有所增加，大脑区域之间的连接也有所改变，这表明突触细化存在缺陷。atg 7缺陷的小胶质细胞中突触体降解受损，与atg 7缺陷的小胶质细胞共培养的神经元中未成熟的树突丝状伪足增加。据我们所知，我们的研究结果是第一个显示小胶质细胞自噬在突触和神经行为调节中的作用。我们期望我们的研究结果是一个起点，更全面的研究小胶质细胞自噬在ASD和推定的治疗方法的发展。
Autism spectrum disorders (ASDs) are neurodevelopmental disorders caused by various genetic and environmental factors that result in synaptic abnormalities. ASD development is suggested to involve microglia, which have a role in synaptic refinement during development. Autophagy and related pathways are also suggested to be involved in ASDs. However, the precise roles of microglial autophagy in synapses and ASDs are unknown. Here, we show that microglial autophagy is involved in synaptic refinement and neurobehavior regulation. We found that deletion of atg7, which is vital for autophagy, from myeloid cell-specific lysozyme M-Cre mice resulted in social behavioral defects and repetitive behaviors, characteristic features of ASDs. These mice also had increases in dendritic spines and synaptic markers and altered connectivity between brain regions, indicating defects in synaptic refinement. Synaptosome degradation was impaired in atg7-deficient microglia and immature dendritic filopodia were increased in neurons co-cultured with atg7-deficient microglia. To our knowledge, our results are the first to show the role of microglial autophagy in the regulation of the synapse and neurobehaviors. We anticipate our results to be a starting point for more comprehensive studies of microglial autophagy in ASDs and the development of putative therapeutics.
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影响因子：
11
作者：
Durand CM;Perroy J;Loll F;Perrais D;Fagni L;Bourgeron T;Montcouquiol M;Sans N
通讯作者：
Sans N
DOI：
10.1023/a:1024134312173
发表时间：
2002-03-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Benavides-Piccione, R;Ballesteros-Yáñez, I;Yuste, R
通讯作者：
Yuste, R
影响因子：
13.3
作者：
Cho, Mi-Hyang;Cho, Kwangmin;Yoon, Seung-Yong
通讯作者：
Yoon, Seung-Yong
影响因子：
30.8
作者：
Helsmoortel, Celine;Vulto-van Silfhout, Anneke T.;Coe, Bradley P.;Vandeweyer, Geert;Rooms, Liesbeth;van den Ende, Jenneke;Schuurs-Hoeijmakers, Janneke H. M.;Marcelis, Carlo L.;Willemsen, Marjolein H.;Vissers, Lisenka E. L. M.;Yntema, Helger G.;Bakshi, Madhura;Wilson, Meredith;Witherspoon, Kali T.;Malmgren, Helena;Nordgren, Ann;Anneren, Goran;Fichera, Marco;Bosco, Paolo;Romano, Corrado;de Vries, Bert B. A.;Kleefstra, Tjitske;Kooy, R. Frank;Eichler, Evan E.;Van der Aa, Nathalie
通讯作者：
Van der Aa, Nathalie
DOI：
10.1038/nri3532
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Deretic V;Saitoh T;Akira S
通讯作者：
Akira S