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PNAS:大脑和小脑皮质中上百种代谢物的含量的测定

来源:上海生命科学研究院 2011-04-13 15:29

人类区别于其它哺乳动物的一大特征是拥有最大和最复杂的大脑。长期以来,人脑的特征被认为跟脑部代谢水平有关。事实上,人们的确在基因表达谱或者氨基酸序列上发现过一些表现出人特异的基因参与了代谢途径。但是,几乎没有人测量人类和其它灵长类脑部代谢物的含量及其变化规律的差异。

由中科院上海生命科学研究院计算生物学所马普青年科学家小组组长Philipp Khaitovich研究员带领的研究团队利用气相色谱-质谱联用法,测量了不同年龄段,人、黑猩猩和恒河猴大脑和小脑皮质中上百种代谢物的含量,并发现88%的代谢物的含量随着年龄变化呈现出有规则的变化,而且有77%的变化在不同物种中有差异。尽管总体来说,代谢物在物种之间的变化与这些物种的系统进化是一致的,但是人类特异的代谢水平的变化在大脑皮质中是小脑皮质的四倍。这些人类特异的代谢水平的变化与合成这些代谢物的酶的表达谱相一致,并涉及到与突触传导、学习和记忆有关的通路。

该项研究成果于3月28日在线发表于美国《国家科学院院刊》(PNAS)。该研究得到了国家科技部、中国科学院、上海生命科学研究院、德国马普学会以及德国联邦教育与研究部的支持。(生物谷Bioon.com)

生物谷推荐原文出处:

PNAS  doi: 10.1073/pnas.1019164108

Rapid metabolic evolution in human prefrontal cortex

Xing Fua,1, Patrick Giavaliscob,1, Xiling Liua,1, Gareth Catchpoleb, Ning Fuc, Zhi-Bin Ningc, Song Guoa, Zheng Yana, Mehmet Somela,d, Svante P??bod, Rong Zengc,2, Lothar Willmitzerb,2, and Philipp Khaitovicha,d,2

Abstract

Human evolution is characterized by the rapid expansion of brain size and drastic increase in cognitive capabilities. It has long been suggested that these changes were accompanied by modifications of brain metabolism. Indeed, human-specific changes on gene expression or amino acid sequence were reported for a number of metabolic genes, but actual metabolite measurements in humans and apes have remained scarce. Here, we investigate concentrations of more than 100 metabolites in the prefrontal and cerebellar cortex in 49 humans, 11 chimpanzees, and 45 rhesus macaques of different ages using gas chromatography–mass spectrometry (GC-MS). We show that the brain metabolome undergoes substantial changes, both ontogenetically and evolutionarily: 88% of detected metabolites show significant concentration changes with age, whereas 77% of these metabolic changes differ significantly among species. Although overall metabolic divergence reflects phylogenetic relationships among species, we found a fourfold acceleration of metabolic changes in prefrontal cortex compared with cerebellum in the human lineage. These human-specific metabolic changes are paralleled by changes in expression patterns of the corresponding enzymes, and affect pathways involved in synaptic transmission, memory, and learning.

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