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: 1440624
• 负责人: Magdalena Muchlinski
• 金额: $ 19.17万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1440624&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，特别是对于已经进化出非常大和复杂的大脑的生物体。人类和其他灵长类动物最明显的特征之一是相对于身体大小的大脑大小。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都大，但与其他哺乳动物相比，它们的基础代谢率（衡量身体能量利用的指标）并没有增加，这就提出了一个问题，即如何满足如此大的大脑的高能量成本。这种趋势表明，当大脑体积增加时，身体中另一个需要能量的组织会产生能量平衡;如果我们总体上没有使用更多的能量，那么可以投资于身体另一部分的能量可能会被用来为我们的大脑提供燃料。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，而人类的大脑尺寸增加最明显，与其他哺乳动物相比，整体肌肉质量减少了50%。因此，这项研究验证了骨骼肌与大脑直接竞争葡萄糖和氧气的假设，从而通过限制肌肉质量来满足大大脑尺寸的高能量需求，构成骨骼肌生长和维持与大脑之间的能量权衡。生长和维持。 如果大脑确实限制了肌肉质量，那么1）更大的大脑应该与骨骼肌质量的减少有关; 2）I型肌纤维的百分比（一种以类似于脑细胞的方式使用能量的肌肉细胞[葡萄糖，一种糖]）应该显示出相对于较大的大脑尺寸的相对减少;以及3）肌肉质量发育应被抑制，直到脑发育完成，并且一旦完成，肌肉质量发育应增加。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，包括一系列大脑大小并代表所有发育阶段。然后将分析每个物种产生的肌肉能量使用概况与大脑大小变化的关系，并将结果应用于理解大脑大小与进化代谢策略之间的相互作用。减少肌肉质量可能使灵长类动物如人类易患某些代谢紊乱（例如，2型糖尿病）;因此，了解是否存在这种限制具有重要的健康意义。最终，收集到的数据可以被纳入生长和发育以及生物力学的研究中，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民族服务的机构，该项目将促进服务不足和代表性不足的人口的研究进步。