通过氢和碳-13核磁共振波谱揭示的精神分裂症动物模型中突触体的代谢变化

Metabolic Changes in Synaptosomes in an Animal Model of Schizophrenia Revealed by H and H,C NMR Spectroscopy.

作者信息

Barnett Brian R, Fathi Fariba, Falco Cobra Paulo, Yi Sue Y, Anderson Jacqueline M, Eghbalnia Hamid R, Markley John L, Yu John-Paul J

机构信息

Neuroscience Training Program, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, Madison, WI 53705, USA.

Biochemistry Department, University of Wisconsin-Madison, Madison, WI 53706, USA.

出版信息

Metabolites. 2020 Feb 23;10(2):79. doi: 10.3390/metabo10020079.

DOI:10.3390/metabo10020079

PMID:32102223

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7074231/

Abstract

Synaptosomes are isolated nerve terminals that contain synaptic components, including neurotransmitters, metabolites, adhesion/fusion proteins, and nerve terminal receptors. The essential role of synaptosomes in neurotransmission has stimulated keen interest in understanding both their proteomic and metabolic composition. Mass spectrometric (MS) quantification of synaptosomes has illuminated their proteomic composition, but the determination of the metabolic composition by MS has been met with limited success. In this study, we report a proof-of-concept application of one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy for analyzing the metabolic composition of synaptosomes. We utilize this approach to compare the metabolic composition synaptosomes from a wild-type rat with that from a newly generated genetic rat model ( svΔ2), which qualitatively recapitulates clinically observed early truncations associated with schizophrenia. This study demonstrates the feasibility of using NMR spectroscopy to identify and quantify metabolites within synaptosomal fractions.

摘要

突触小体是分离出的神经末梢，包含突触成分，包括神经递质、代谢物、黏附/融合蛋白和神经末梢受体。突触小体在神经传递中的重要作用激发了人们对了解其蛋白质组学和代谢组成的浓厚兴趣。质谱（MS）对突触小体的定量分析揭示了它们的蛋白质组组成，但通过MS确定代谢组成的成效有限。在本研究中，我们报告了一维和二维核磁共振（NMR）光谱在分析突触小体代谢组成方面的概念验证应用。我们利用这种方法比较了野生型大鼠与新生成的基因大鼠模型（svΔ2）的突触小体代谢组成，该模型定性地概括了临床上观察到的与精神分裂症相关的早期截断。这项研究证明了使用NMR光谱鉴定和定量突触小体组分中代谢物的可行性。