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: 1440519
• 负责人: Rui Diogo
• 金额: $ 1.87万
• 依托单位: Howard University
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1440519&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.

大脑的生长和维护需要大量的能源投资，尤其是对于已经进化出非常大而复杂的大脑的生物。人类和其他灵长类动物最定义的特征之一是相对于体型的大脑大小。然而，与其他哺乳动物相比，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，人类和非人类灵长类动物的基础代谢率（人体利用率的量度）并未显示出来，这提出了如何满足如此大脑的高能成本的问题。这种趋势表明，当脑大小增加时，体内另一种能量的组织有一个能量的权衡。如果我们整体上不使用更多的能量，那么可以投资于身体另一部分的能量很可能被用来助长我们的大脑。初步研究表明，与其他动物相比，灵长类动物的肌肉质量低，而与其他哺乳动物相比，大脑大小最显着的人的肌肉质量最为明显。因此，这项研究检验了以下假设：骨骼肌与大脑在葡萄糖和氧气中直接竞争，从而通过约束肌肉质量来满足大脑大小的高能量需求，构成骨骼肌肉生长和脑部生长以及大脑生长和维持和维持之间的能量折衷。 如果大脑确实限制了肌肉质量，则1）较大的大脑应与骨骼肌质量减少有关； 2）I型肌肉纤维的百分比（一种使用能量[葡萄糖，一种类型的糖]的肌肉细胞的百分比与较大的脑大小相关； 3）应抑制肌肉质量发育直到脑生长完成，一旦完成，肌肉质量发育就应该增加。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，包括一系列脑大小，代表所有发育阶段。然后，将分析每个物种的肌肉能量利用曲线，以与脑大小的变化有关，结果适用于了解脑大小与进化的代谢策略之间的相互作用。减少肌肉质量可能具有诱发的灵长类动物（例如人类）对某些代谢性疾病（例如2型糖尿病）；因此，了解是否存在这种约束具有重要的健康影响。最终，收集到的数据可以纳入生长和发育研究以及生物力学，结果可能会鼓励生物医学基因疗法的发展。这项研究还将为其他学科的科学家提供丰富的数据库，该学科的重点是动物解剖学和生理学，促进和扩大未来的研究。该协作项目汇集了国际研究人员，并将支持来自美国三所大学的多个本科生和研究生的培训。由于这些大学中的两所在EPSCOR国家，其中一所是历史悠久的少数派服务机构，该项目将促进服务不足和代表性不足的人口的进步。