CAREER: Understanding the persistent effects of the food environment on taste sensation

职业：了解食物环境对味觉的持续影响

• 批准号: 1941822
• 负责人: Mohammed Akaaboune
• 金额: $ 135.11万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1941822&HistoricalAwards=false
• 关键词: CAREER; Understanding; persistent; effects; food

Life experiences like trauma and abuse can have lasting effects on the brain, altering the behavior of animals for a lifetime. This occurs because a memory of the event is written and persists beyond the environmental circumstances' change. These memories limit the range of possible behavioral responses to future stimuli and may lock animals into maladaptive patterns of behavior. How these memories are written, how they influence behaviors, and how they become etched in the brain has been hard to study. Here the investigators will implement a research and educational platform to understand the enduring effects of the dietary environment on the brain. Specifically, they will use the genetically tractable model organism Drosophila melanogaster (fruit fly) to study how high dietary sugar, which is prevalent in society, permanently changes taste sensation and feeding behavior. The broad impact goal is to develop an outreach platform to disseminate accurate and accessible knowledge on the lasting effects of environmental influences on the brain. The target audience of that platform are people of all ages and challenges traditional campus boundaries. Together, the intellectual and the broader impact this project have implications for the field of public health by uncovering and communicating the mechanisms through which the environment, and especially diet, has a lasting effect on brain and behavior. Diet composition alters the peripheral processing of sensory information, and this, in turn, influences food choice and food intake. The principal investigator recently showed that high dietary sugar decreases the responses of the sensory neurons to sweetness in D. melanogaster. Furthermore, the investigator established a causal link between changes in sweet sensation to the action of the Hexosamine Biosynthesis Pathway (HPB), a metabolic signaling pathway activated by high levels of sugar. Preliminary experiments show that the HPB requires the gene silencing activity of the Polycomb Repressive Complex 2 (PRC2) to decrease sweet taste, which provides a mechanism to link food environment and behavior. This project uncovers the molecular mechanisms through which PRC2 leads to persistent changes in the physiology of the sweet sensing cells by (1) determining the effect of PRC2 manipulations on the activity of the sweet sensing neurons; (2) establishing how PRC2 targets affect the physiology of the sensory neurons to decrease sweet taste function; and (3) identifying how sweet taste deficits persist beyond exposure to the high sugar environment. These aims are pursued using a combination of genetic, molecular, and behavioral approaches.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

像创伤和虐待这样的生活经历会对大脑产生持久的影响，改变动物一生的行为。发生这种情况是因为事件的记忆被写入并持续超过环境情况的变化。这些记忆限制了动物对未来刺激的可能行为反应范围，并可能将动物锁定在适应不良的行为模式中。这些记忆是如何书写的，它们是如何影响行为的，以及它们是如何铭刻在大脑中的，这些都很难研究。在这里，研究人员将实施一个研究和教育平台，以了解饮食环境对大脑的持久影响。具体来说，他们将使用遗传学上易于处理的模式生物果蝇（果蝇）来研究社会中普遍存在的高糖饮食如何永久改变味觉和进食行为。广泛影响的目标是建立一个外联平台，传播关于环境影响对大脑的持久影响的准确和可获取的知识。该平台的目标受众是所有年龄段的人，并挑战传统的校园界限。总之，该项目的智力和更广泛的影响对公共卫生领域有影响，通过揭示和交流环境，特别是饮食，对大脑和行为产生持久影响的机制。饮食组成改变了感官信息的外围处理，这反过来又影响了食物的选择和食物的摄入。首席研究员最近表明，高糖饮食会降低D。黑腹菌此外，研究人员建立了甜味变化与己糖胺生物合成途径（HPB）作用之间的因果关系，HPB是一种由高水平糖激活的代谢信号通路。初步实验表明，HPB需要Polycomb Repressive Complex 2（PRC 2）的基因沉默活性来降低甜味，这提供了一种将食物环境和行为联系起来的机制。本项目通过以下方式揭示PRC 2导致甜味感觉细胞生理学持续变化的分子机制：（1）确定PRC 2操纵对甜味感觉神经元活性的影响;（2）确定PRC 2靶标如何影响感觉神经元的生理学以降低甜味功能;（3）确定PRC 2靶点如何影响甜味感觉神经元的生理学以降低甜味感觉功能。以及（3）确定甜味缺陷如何在暴露于高糖环境之后持续存在。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Persistent epigenetic reprogramming of sweet taste by diet.

• DOI: 10.1126/sciadv.abc8492
• 发表时间: 2020-11
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Vaziri A;Khabiri M;Genaw BT;May CE;Freddolino PL;Dus M
• 通讯作者: Dus M

Brain on food: The neuroepigenetics of nutrition.

• DOI: 10.1016/j.neuint.2021.105099
• 发表时间: 2021-10
• 期刊: Neurochemistry international
• 影响因子: 4.2
• 作者: Vaziri A;Dus M
• 通讯作者: Dus M

Confection Confusion: Interplay Between Diet, Taste, and Nutrition.

• DOI: 10.1016/j.tem.2020.11.011
• 发表时间: 2021-03
• 期刊: Trends in endocrinology and metabolism: TEM
• 作者: May CE;Dus M
• 通讯作者: Dus M

Crème de la Créature: Dietary Influences on Behavior in Animal Models.

• DOI: 10.3389/fnbeh.2021.746299
• 发表时间: 2021
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Sarangi M;Dus M
• 通讯作者: Dus M

High-sucrose diet exposure is associated with selective and reversible alterations in the rat peripheral taste system.

高核饮食暴露与大鼠外围味觉系统的选择性和可逆变化有关。

• DOI: 10.1016/j.cub.2022.07.063
• 发表时间: 2022-10-10
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Sung, Hayeon;Vesela, Iva;Driks, Hannah;Ferrario, Carrie R.;Mistretta, Charlotte M.;Bradley, Robert M.;Dus, Monica
• 通讯作者: Dus, Monica