谢鹏+魏泓:菌群失调对大脑蛋白磷酸化的影响
  • 无菌小鼠(与有菌小鼠相比)和接受抑郁症患者粪菌移植(FMT)的小鼠(与接受健康人FMT的小鼠相比)存在行为异常,伴随海马体中大量的蛋白磷酸化异常;
  • 接受抑郁症FMT的小鼠还在外周和大脑中呈现脂质和氨基酸的代谢紊乱;
  • 海马体蛋白磷酸化失调与谷氨酸能神经递质系统的扰动相关,CAMKII-CREB信号通路是主要被扰动的细胞过程;
  • 首次证明肠道菌群失调会损伤神经元中的剪接体功能,其中NCBP1磷酸化或是关键的致病靶标。
主编推荐语
mildbreeze
蛋白磷酸化等翻译后修饰是调控蛋白质功能的重要机制。Translational Psychiatry近期发表了重庆医科大学谢鹏团队与第三军医大学魏泓团队的合作研究,表明肠道菌群可对大脑的蛋白磷酸化产生广泛影响,为理解菌群在抑郁症等精神疾病和行为调控中的作用带来新启示。
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Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice

整合磷酸化蛋白质组学和代谢组学分析揭示肠道菌群失小鼠的海马体中被扰动的途径

10.1038/s41398-020-01024-9

2020-10-13, Article

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The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota–gut–brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify the global phosphorylation dynamics in hippocampus tissue in germ-free mice and specific pathogen-free mice (GF vs SPF), fecal microbiota transplantation (FMT) model (“depression microbiota” and the “healthy microbiota” recipient mice). As a result, 327 phosphosites of 237 proteins in GF vs SPF, and 478 phosphosites of 334 proteins in “depression microbiota” vs “healthy microbiota” recipient mice were identified as significant. These phosphorylation dysregulations were consistently associated with glutamatergic neurotransmitter system disturbances. The FMT mice exhibited disturbances in lipid metabolism and amino acid metabolism in both the periphery and brain through integrating phosphoproteomic and metabolomic analysis. Moreover, CAMKII-CREB signaling pathway, in response to these disturbances, was the primary common perturbed cellular process. In addition, we demonstrated that the spliceosome, never directly implicated in mental disorders previously, was a substantially neuronal function disrupted by gut microbiota dysbiosis, and the NCBP1 phosphorylation was identified as a novel pathogenic target. These results present a new perspective to study the pathologic mechanisms of gut microbiota dysbiosis related depression and highlight potential gut-mediated therapies for depression.

First Authors:
Haiyang Wang

Correspondence Authors:
Hong Wei,Peng Xie

All Authors:
Haiyang Wang,Lanxiang Liu,Xuechen Rao,Benhua Zeng,Ying Yu,Chanjuan Zhou,Li Zeng,Peng Zheng,Juncai Pu,Shaohua Xu,Ke Cheng,Hanping Zhang,Ping Ji,Hong Wei,Peng Xie

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