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

基本信息

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

项目摘要

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.

创伤和虐待等生活经历会对大脑产生持久影响，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在环境情况发生变化后仍然存在。这些记忆限制了对未来刺激可能的行为反应范围，并可能使动物陷入适应不良的行为模式。这些记忆是如何书写的、它们如何影响行为以及它们如何铭刻在大脑中一直很难研究。研究人员将在这里建立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，他们将使用遗传易处理的模式生物果蝇（果蝇）来研究社会中普遍存在的高膳食糖如何永久改变味觉和进食行为。广泛的影响目标是开发一个外展平台，传播有关环境影响对大脑持久影响的准确且易于理解的知识。该平台的目标受众是各个年龄段的人，挑战传统校园的界限。总之，该项目通过揭示和传达环境（尤其是饮食）对大脑和行为产生持久影响的机制，对公共卫生领域产生了影响。饮食结构改变了感官信息的外围处理，进而影响食物选择和食物摄入。主要研究人员最近表明，高膳食糖会降低黑腹果蝇感觉神经元对甜味的反应。此外，研究人员还建立了甜味感觉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途径。初步实验表明，HPB需要多梳抑制复合物2（PRC2）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。该项目通过以下方式揭示了 PRC2 导致甜味感觉细胞生理学持续变化的分子机制：(1) 确定 PRC2 操作对甜味感觉神经元活动的影响； (2) 确定 PRC2 靶标如何影响感觉神经元的生理机能以降低甜味功能； (3) 确定甜味缺陷在暴露于高糖环境后如何持续存在。这些目标是通过结合遗传、分子和行为方法来实现的。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力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

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
作者：
May CE;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.

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

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