Neurobiology of taste, smell and eating behaviors: Molecular and neuronal mechanism of sensory science and metabolism along the gut-brain-axis in animal models.

味觉、嗅觉和饮食行为的神经生物学：动物模型中沿肠脑轴的感觉科学和代谢的分子和神经元机制。

• 批准号: 10256462
• 负责人: Paule Joseph
• 金额: $ 28.33万
• 依托单位: NATIONAL INSTITUTE OF NURSING RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10256462
• 关键词: Addictive Behavior; Animal Model; Animals; Behavior; Biological; Brain region; CD36 gene; Cessation of life; Chronic; Clinical Protocols; Collaborations; Complement; Consumption; Corpus striatum structure; Diet; Dietary Intervention; Disease; Eating; Eating Behavior; Electrophysiology (science); Energy Intake; Extramural Activities; Fatty acid glycerol esters; Food; Functional disorder; Gene Expression; Genes; Genetic; Genomics; Goals; Health; Immunohistochemistry; Individual; Intervention; Laboratories; Lead; Mediator of activation protein; Metabolic; Metabolic Pathway; Metabolic dysfunction; Metabolism; Molecular; Mus; Neurobiology; Neurons; Obese Mice; Obesity; Oral cavity; Pain; Palate; Pattern; Pharmacology; Phenotype; Physiological; Protocols documentation; Publications; Quality of life; Research; Role; Science; Sensory; Smell Perception; System; Taste Perception; Techniques; Tissues; Translating; Weight; addiction; behavioral study; brain tissue; design; differential expression; gut-brain axis; hedonic; improved; interest; olfactory bulb; opioid overdose; opioid use; opioid use disorder; optogenetics; pain perception; pleasure; preclinical study; prescription pain reliever; response; sensory mechanism; sensory system; sugar; transcriptome sequencing; transcriptomics

The Sensory Science and Metabolism Unit was established in October 2017 (FY18). This fiscal year FY20, we continued to study sensory science and metabolism in animal models of obesity and metabolic dysfunction. We established animal projects focused on the overall goal of the laboratory. This should complement the clinical protocols and enable us to study biological mechanisms of sensory science and metabolism- including the underlying pathophysiology of maladaptive behaviors and assess potential interventions. To achieve this goal, we have been developing protocols that utilize techniques including optogenetics, electrophysiology, transcriptomic studies, immunohistochemistry, and behavioral studies. Two new collaborations have been established with intramural and extramural collaborators. Metabolic Dysfunction and Sensory Science: The rise in obesity is associated with an increased availability of highly palatable and energy-dense foods, rich in fat and sugar. The pleasure driven value of energy-dense foods promotes their preferential consumption which can lead to increased caloric intake and obesity. Taste, olfaction, and other chemosensory systems contribute to hedonic processing and eating behavior. Thus, there is growing interest in the role of taste in obesity, including the study of the biological mediators of fat-taste and associated olfaction as potential targets for pharmacologic and nutritional interventions. As part of this overall umbrella we began examining the effect of diet (high fat) on genes a project led by Rosario Jaime-Lara with support from Brianna Brooks and Claudia Colina-Prisco: The growing interest in the role of fat taste in obesity highlights the importance of taste and diet in eating behavior and health. Studies of taste-related genes have focused on gene expression in the mouth. However, taste-related genes are located throughout the body, including in brain regions known to regulate eating and taste. Thus, we aimed to examine genetic differences in taste and metabolic related genes in brain tissue of obese and normal-weight mice. We used qPCR to examine 64 taste and metabolic related genes in the striatum, olfactory-bulb, and striatum. We also used RNA sequencing to examine transcriptomic-level differences in these three brain regions. We found changes in metabolic gene expression of obese mice (compared to normal-weight mice). We also found increased expression of CD36, a gene associated with fat-taste. Additionally, RNA sequencing revealed genes were differentially expressed in the striatum (274 genes) and in olfactory bulb (19 genes). Lastly, we are working to characterize D1 and D2 MSNs in mice following a HFD, including their chemosensory phenotype and activity patterns. Sensory System Disturbances: Opioid use disorders, including abuse of prescription pain relievers, are a national crisis with devastating consequences, including a rapidly escalating number of opioid overdose-related deaths. The physiological mechanisms underlying pain, addiction, and their intersection are not fully understood. The purpose of this research is to study genomic changes across multiple phenotypes of pain, opioid use, and opioid use disorder. The goal is to improve understanding of relationship between disturbances in sensory systems and disease. This includes individual and addiction-induced differences in thresholds and responses to taste, olfaction, and changes in pain perception. Projects have started and preliminary findings have been obtained. No publication are available for these projects yet.

感官科学和代谢部门成立于2017年10月（FY 18）。2020财年，我们继续在肥胖和代谢功能障碍的动物模型中研究感觉科学和代谢。我们建立了专注于实验室总体目标的动物项目。这应该是对临床方案的补充，使我们能够研究感觉科学和代谢的生物机制--包括适应不良行为的潜在病理生理学，并评估潜在的干预措施。为了实现这一目标，我们一直在开发利用包括光遗传学、电生理学、转录组学研究、免疫组织化学和行为研究在内的技术的方案。与校内和校外合作者建立了两个新的合作关系。 代谢功能障碍和感官科学： 肥胖症的增加与富含脂肪和糖的高可口和能量密集的食物的可获得性增加有关。高能量食物的快乐驱动价值促进了它们的优先消费，这可能导致热量摄入增加和肥胖。味觉、嗅觉和其他化学感觉系统有助于享乐加工和进食行为。因此，人们越来越关注味觉在肥胖中的作用，包括研究脂肪味觉和相关嗅觉的生物介质作为药理学和营养干预的潜在目标。 作为这一总体保护伞的一部分，我们开始研究饮食（高脂肪）对基因的影响，这是一个由罗萨里奥Jaime-Lara领导的项目，得到了Brianna布鲁克斯和Claudia Colina-Prisco的支持：对脂肪口味在肥胖中的作用越来越感兴趣，突出了口味和饮食在饮食行为和健康中的重要性。味觉相关基因的研究主要集中在口腔中的基因表达。然而，与味觉相关的基因遍布全身，包括已知调节饮食和味觉的大脑区域。因此，我们的目的是研究肥胖和正常体重小鼠脑组织中味觉和代谢相关基因的遗传差异。我们使用qPCR检测了纹状体、嗅球和纹状体中的64个味觉和代谢相关基因。我们还使用RNA测序来检查这三个大脑区域的转录水平差异。我们发现了肥胖小鼠代谢基因表达的变化（与正常体重小鼠相比）。我们还发现了与脂肪味道相关的基因CD 36的表达增加。此外，RNA测序显示基因在纹状体（274个基因）和嗅球（19个基因）中差异表达。 最后，我们正在研究HFD后小鼠中D1和D2 MSN的特征，包括它们的化学感受表型和活动模式。 感觉系统障碍： 阿片类药物使用障碍，包括滥用处方止痛药，是一场具有破坏性后果的国家危机，包括阿片类药物过量相关死亡人数迅速上升。疼痛、成瘾及其交叉的生理机制尚未完全了解。本研究的目的是研究疼痛，阿片类药物使用和阿片类药物使用障碍的多种表型的基因组变化。目的是提高对感觉系统紊乱与疾病之间关系的理解。这包括个体和成瘾诱导的阈值差异和对味觉、嗅觉的反应，以及疼痛感知的变化。 项目已经启动，并已获得初步调查结果。目前还没有关于这些项目的出版物。