Collaborative Research: Skeletal muscle constraint on relative brain size

合作研究：骨骼肌对相对大脑大小的限制

• 批准号: 1734668
• 负责人: Magdalena Muchlinski
• 金额: $ 9.57万
• 依托单位: University of North Texas Health Science Center at Fort Worth
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1734668&HistoricalAwards=false
• 关键词: Collaborative; Research; Skeletal; muscle; constraint

The growth and maintenance of the brain require substantial investments of energy, most especially for organisms which have evolved very large and complex brains. One of the most defining characteristics for the human species and the other primates is large brain size relative to body size. Yet, despite having larger brains than most other mammals, human and nonhuman primates do not show an increase in their basal metabolic rate (a measure of energy utilization by the body) compared to other mammals, raising the question of how the high energetic cost of such large brains is met. This trend suggests that there is an energetic trade-off with another energy-demanding tissue in the body when brain size increases; if we are not using more energy overall, then energy that could be invested in another part of our body is instead likely being utilized to fuel our large brains. Preliminary research shows that primates have low muscle mass when compared to other animals, and humans, who have the most notable increase in brain size, show a 50% reduction in overall muscle mass when compared with other mammals. This research therefore tests the hypothesis that skeletal muscle is in direct competition with the brain for glucose and oxygen, such that the high energetic demands of large brain size are met through constraining muscle mass, constituting an energetic tradeoff between skeletal muscle growth and maintenance, and brain growth and maintenance. If the brain does constrain muscle mass, then 1)larger brains should be associated with decreased skeletal muscle mass; 2)the percentage of type I muscle fibers (a type of muscle cell that uses energy [glucose, a type of sugar] in a similar fashion to brain cells) should show a relative decrease in relation to larger brain size; and 3)muscle mass development should be suppressed until brain growth is complete, and once complete, there should be an increase in muscle mass development. To test these predictions, muscle tissue samples will be collected from a diverse array of primate specimens, comprising a range of brain sizes and representing all developmental stages. The generated muscle energy use profiles for each species will then be analyzed in relation to variation in brain size, with the results applied to understanding the interaction between brain size and evolved metabolic strategies. Reducing muscle mass may have predisposed primates such as humans to certain metabolic disorders (e.g., type 2 diabetes); thus, understanding if there is such a constraint has important health implications. Ultimately, the data collected can be incorporated into studies of growth and development, as well as biomechanics, and the results may encourage development of biomedical gene therapies. The research also will provide a rich database for scientists in other disciplines focusing on animal anatomy and physiology, facilitating and expanding future research. The collaborative project brings together international researchers, and will support the training of multiple undergraduate and graduate students from three US universities. As two of these universities are in EPSCoR states, and one is a historically minority-serving institution, the project will foster research advancement for underserved and underrepresented populations.

大脑的生长和维持需要大量的能量投入，尤其是对于已经进化出非常大和复杂的大脑的生物体来说。人类和其他灵长类动物最明显的特征之一是大脑相对于身体尺寸较大。然而，尽管人类和非人类灵长类动物的大脑比大多数其他哺乳动物更大，但与其他哺乳动物相比，它们的基础代谢率（身体能量利用的衡量标准）并没有增加，这就提出了如何满足如此大的大脑的高能量成本的问题。这一趋势表明，当大脑尺寸增加时，与体内另一个需要能量的组织之间存在能量权衡。如果我们总体上没有使用更多的能量，那么本可以投入到我们身体其他部位的能量反而可能被用来为我们的大大脑提供能量。初步研究表明，与其他动物相比，灵长类动物的肌肉质量较低，而大脑尺寸增加最显着的人类，与其他哺乳动物相比，整体肌肉质量减少了 50%。因此，这项研究检验了这样的假设：骨骼肌与大脑直接竞争葡萄糖和氧气，从而通过限制肌肉质量来满足大大脑的高能量需求，在骨骼肌生长和维持与大脑生长和维持之间构成能量权衡。 如果大脑确实限制了肌肉质量，那么1）较大的大脑应该与骨骼肌质量的减少有关； 2）I型肌纤维（一种以与脑细胞类似的方式使用能量[葡萄糖，一种糖]的肌肉细胞）的百分比应该随着大脑尺寸的增大而相对减少； 3）肌肉质量的发育应该受到抑制，直到大脑生长完成，一旦完成，肌肉质量的发育应该会增加。为了测试这些预测，将从各种灵长类动物标本中收集肌肉组织样本，其中包括一系列大脑尺寸并代表所有发育阶段。然后，将根据大脑大小的变化对生成的每个物种的肌肉能量使用概况进行分析，并将结果应用于理解大脑大小和进化的代谢策略之间的相互作用。减少肌肉质量可能会使灵长类动物（例如人类）容易患某些代谢疾病（例如 2 型糖尿病）；因此，了解是否存在这样的限制具有重要的健康意义。最终，收集的数据可以纳入生长和发育以及生物力学的研究，其结果可能会鼓励生物医学基因疗法的发展。该研究还将为专注于动物解剖学和生理学的其他学科的科学家提供丰富的数据库，促进和扩大未来的研究。该合作项目汇集了国际研究人员，并将支持来自三所美国大学的多名本科生和研究生的培训。由于其中两所大学位于 EPSCoR 州，其中一所是历史上为少数族裔服务的机构，因此该项目将促进服务不足和代表性不足的人群的研究进步。