肠道菌群对下丘脑神经肽和蛋白的影响
  • 用整合无标记和10-plex等压标记定量方法,比较无菌和常规饲养小鼠下丘脑的神经肽和蛋白质谱;
  • 从63个神经肽前体和3971个蛋白中,鉴定出2943个内源性肽,其中368个肽在这两类小鼠间有显著差异,主要来源于分泌粒蛋白、磷脂酰乙醇胺结合蛋白1、ProSAAS和脑啡肽原蛋白;
  • 这些神经肽的功能和相关蛋白途径与食物摄取、昼夜节律和调节学习记忆有关;
  • 研究证实了肠道菌群调节大脑信号分子的重要性,需对神经肽和蛋白进一步验证。
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Analytical Chemistry近期发表的一项研究,采用整合无标记和基于DiLeu的定量方法,对比了无菌和有菌小鼠下丘脑的神经肽组和蛋白质组的差异,表明肠道菌群或通过影响这些神经肽和蛋白来参与对宿主行为和认知功能的调控。
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Integrated Label-Free and 10-plex DiLeu Isobaric Tag Quantitative Methods for Profiling Changes in the Mouse Hypothalamic Neuropeptidome and Proteome: Assessment of the Impact of the Gut Microbiome

分析小鼠下丘脑神经肽组和蛋白质组变化的整合无标记和10-plex DiLeu等压标记定量方法:评估肠道微生物组的影响

10.1021/acs.analchem.0c02939

2020-09-14, Article

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Gut microbiota can regulate host physiological and pathological status through gut-brain communications or pathways. However, the impact of the gut microbiome on neuropeptides and proteins involved in regulating brain functions and behaviors is still not clearly understood. To address the problem, integrated label-free and 10-plex DiLeu isobaric tag-based quantitative methods were implemented to compare the profiling of neuropeptides and proteins in the hypothalamus of germ-free (GF) vs. conventionally-raised (ConvR) mice. A total of 2,943 endogenous peptides from 63 neuropeptide precursors and 3,971 proteins in the mouse hypothalamus were identified. Among these 368 significantly changed peptides (fold changes over 1.5, and p-value < 0.05), 73.6% of the peptides showed higher levels in GF-mice than in ConvR-mice, and 26.4% of the peptides had higher levels in ConvR-mice than in GF-mice. These peptides were mainly from Secretogranin-2, Phosphatidylethanolamine-binding protein-1, ProSAAS, and Proenkephalin-A. Quantitative proteomic analysis employing DiLeu isobaric tags revealed that 282 proteins were significantly up- or down-regulated (fold changes over 1.2, and p-value < 0.05) among the 3,277 quantified proteins. These neuropeptides and proteins were mainly involved in regulating behaviors, transmitter release, signaling pathways, and synapses. Interestingly, pathways including long-term potentiation, long-term depression, and circadian entrainment were involved. In the present study, a combined label-free and 10-plex DiLeu-based quantitative method enable a comprehensive profiling of gut microbiome induced dynamic changes of neuropeptides and proteins in the hypothalamus, suggesting that the gut microbiome might mediate a range of behavioral changes, brain development, learning, and memory through these neuropeptides and proteins.

First Authors:
Rui Liu

Correspondence Authors:
Lingjun Li

All Authors:
Rui Liu,Pingli Wei,Caitlin Keller,Nicola Salvatore Orefice,Yatao Shi,Zihui Li,Junfeng Huang,Yusi Cui,Dustin C Frost,Shuying Han,Tzu-Wen L Cross,Federico E Rey,Lingjun Li

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