The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior.
The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior.
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DOI：
10.1038/mp.2016.182
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发表时间：
2017-02
影响因子：
11
通讯作者：
Diaz Heijtz R
中科院分区：
文献类型：
--
作者：
Arentsen T;Qian Y;Gkotzis S;Femenia T;Wang T;Udekwu K;Forssberg H;Diaz Heijtz R
最近的研究表明，肠道微生物区系调节大脑发育和行为，但其潜在机制仍然知之甚少。在这里，我们证明了来自共生肠道微生物区系的细菌肽聚糖(PGN)可以移位到大脑中，并被先天性免疫系统的特定模式识别受体(PRR)感知。利用表达谱技术，我们证明了两个特异性检测PGN(即PGN识别蛋白和点样受体)的PRR家族和PGN转运体PepT1在男性和女性出生后发育的特定窗口中都高表达。此外，我们发现几个PGN敏感分子和PepT1在发育中的纹状体中的表达对肠道微生物区系的操作(即无菌条件和抗生素治疗)是敏感的。最后，我们使用了PGN识别蛋白2(PGN-Recognition Protein 2，简称PGN-Recognition Protein 2，简称PGN-Recognition Protein 2，PGN-Recognition Protein 2)基因敲除小鼠来检测PGN敏感分子对大脑发育和行为的潜在影响我们证明，缺乏Pglrp2会导致自闭症风险基因c-Met的表达发生变化，并导致社会行为的性别相关性变化，类似于操纵微生物区系的小鼠。这些发现表明，微生物产物对PRRs的中枢激活可能是肠道微生物区系与发育中的大脑之间沟通的信号通路之一。
Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females. Moreover, we show that the expression of several PGN-sensing molecules and PepT1 in the developing striatum is sensitive to manipulations of the gut microbiota (that is, germ-free conditions and antibiotic treatment). Finally, we used the PGN-recognition protein 2 (Pglyrp2) knockout mice to examine the potential influence of PGN-sensing molecules on brain development and behavior. We demonstrate that the absence of Pglyrp2 leads to alterations in the expression of the autism risk gene c-Met, and sex-dependent changes in social behavior, similar to mice with manipulated microbiota. These findings suggest that the central activation of PRRs by microbial products could be one of the signaling pathways mediating the communication between the gut microbiota and the developing brain.