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首页> 外文期刊>Scientific reports. >Microbiota Modulates Behavior and Protein Kinase C mediated cAMP response element-binding protein Signaling
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Microbiota Modulates Behavior and Protein Kinase C mediated cAMP response element-binding protein Signaling

机译：微生物群调节行为和蛋白激酶C介导的cAMP反应元件结合蛋白信号传导

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Evolutionary pressure drives gut microbiota-host coevolution and results in complex interactions between gut microbiota and neural development; however, the molecular mechanisms by which the microbiota governs host behavior remain obscure. Here, we report that colonization early in life is crucial for the microbiota to modulate brain development and behavior; later colonization or deletion of microbiota cannot completely reverse the behaviors. Microarray analysis revealed an association between absence of gut microbiota and expression in cAMP responding element-binding protein (CREB) regulated genes in the hippocampus. The absence of gut microbiota from birth was shown to be associated with decreased CREB expression, followed by decreases of protein kinase C beta (PRKCB) and AMPA receptors expression, and an increase of phosphorylation CREB (pCREB) expression. Microbiota colonization in adolescence restored CREB and pCREB expression, but did not alter PRKCB and AMPARs expression. The removal of the gut microbiota from SPF mice using antibiotics only reduced pCREB expression. These findings suggest that (i) colonization of the gut microbiota early in life might facilitate neurodevelopment via PKC-CREB signaling and (ii) although GF mice and ABX mice display reduced anxiety-related behaviors, the molecular mechanisms behind this might differ.
机译：进化压力驱动肠道菌群与宿主的协同进化，并导致肠道菌群与神经发育之间复杂的相互作用;但是，微生物控制宿主行为的分子机制仍然不清楚。在这里，我们报告说，生命早期的殖民化对于微生物群调节大脑发育和行为至关重要。后来菌群的定植或缺失不能完全逆转这种行为。基因芯片分析揭示了肠道菌群的缺乏与海马中cAMP反应元件结合蛋白（CREB）调控基因表达之间的关联。从出生开始就没有肠道菌群与CREB表达降低有关，随后是蛋白激酶C beta（PRKCB）和AMPA受体表达降低，以及磷酸化CREB（pCREB）表达增加。青春期的菌群定植可恢复CREB和pCREB的表达，但不会改变PRKCB和AMPARs的表达。使用抗生素从SPF小鼠中去除肠道菌群只会降低pCREB的表达。这些发现表明：（i）肠道菌群的早期定居可能通过PKC-CREB信号传导促进神经发育;（ii）尽管GF小鼠和ABX小鼠显示出与焦虑相关的行为减少，但其背后的分子机制可能有所不同。

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