Palatable Food and Synaptic Plasticity

美味的食物和突触可塑性

• 批准号: 7962692
• 负责人: Yvonne Michelle Ulrich-Lai
• 金额: $ 7.85万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7962692
• 关键词: AMPA Receptors; Address; Adrenal Glands; Adult; Affect; Amygdaloid structure; Attenuated; Automobile Driving; Behavior; Behavioral; Brain; Calories; Carbohydrates; Cluster Analysis; Confocal Microscopy; Consumption; Cyclic AMP-Responsive DNA-Binding Protein; Development; Eating; Emotional; Environmental Risk Factor; Fatty acid glycerol esters; Figs - dietary; Food; Food Energy; Future; Gene Expression; Genes; Glutamates; Health Care Costs; Human; Hypothalamic structure; Incidence; Intake; Interneurons; Knowledge; Lesion; Life; Mediating; Mentored Research Scientist Development Award; Modeling; Moods; Motivation; Nature; Neurons; Obesity; Oral; Output; Pathway interactions; Pattern; Physiological; Pituitary Gland; Presynaptic Terminals; Prevention strategy; Property; Public Health; Rattus; Receptor Activation; Recording of previous events; Rewards; Rodent; Role; Saccharin; Self Medication; Signal Pathway; Signal Transduction; Solid; Solutions; Stress; Sucrose; Synapses; Synaptic plasticity; Synaptophysin; Testing; United States; Water; Weight Gain; attenuation; base; biological adaptation to stress; combat; density; drinking; energy balance; hypothalamic-pituitary-adrenal axis; improved; insight; nerve supply; neuromechanism; novel therapeutics; obesity treatment; prevent; public health relevance; relating to nervous system; response; sugar

DESCRIPTION (provided by applicant): Food intake and energy balance are profoundly influenced by stress, and vice versa. However, the neural mechanisms underlying these effects are largely unknown. The long-term objective of this project is to pursue the mechanisms by which stress and food/energy balance interact. More specifically, this proposal seeks to understand how highly palatable foods provide stress relief. These mechanisms are studied using a model of limited palatable food intake in which rats with free access to food and water are given additional twice-daily access to a small amount of sucrose solution or water as a control. In this model, sucrose rats have attenuated hypothalamic-pituitary-adrenal (HPA) axis responses to stress and diminished stress-induced neuronal activation in brain reward regions. Moreover, the calories and other post-ingestive consequences of sucrose are neither sufficient nor necessary for the HPA dampening, suggesting that brain reward regions may mediate the response. The basolateral amygdala (BLA) is a key brain reward region that is also implicated in driving stress responses. Moreover, neural activity in the BLA is necessary for stress-dampening by sucrose, and genes related to synaptic plasticity are up-regulated in the BLA following a history of sucrose intake. Collectively, this suggests that palatable foods may dampen stress responses via synaptic remodeling in the BLA. Thus, the current proposal addresses the hypothesis palatable food causes synaptic reorganization in the BLA. We predict that sucrose intake increases BLA inhibitory tone, leading to less stress-excitatory output. Furthermore, we hypothesize that enhanced inhibitory tone in the BLA is due to increased drive to the intra-BLA inhibitory interneurons. The proposal tests this hypothesis in two specific aims. The first specific aim will test the hypothesis that sucrose intake increases synaptic appositions in a manner consistent with enhanced inhibition of BLA output. This aim will use anatomical approaches to identify and quantify synaptic appositions onto BLA neurons following sucrose intake. The second specific aim will test that hypothesis that sucrose-induced BLA synaptic reorganization is mediated by AMPA receptor activation of pCREB. This aim will use intra-BLA blockade of AMPA receptor activity and CREB/pCREB expression to determine whether this signaling pathway mediates sucrose-induced synaptic reorganization. PUBLIC HEALTH RELEVANCE: When under stress, many people increase their intake of highly palatable (e.g., tasty, high-sugar or high-fat) foods, presumably to help calm or comfort themselves. However, this behavior can increase body weight and contribute to the development of obesity. This project seeks to understand how palatable foods act to decrease the response to stress, thereby providing insight into the motivation to consume these foods and potentially offering new strategies for the prevention and treatment of obesity.

描述（由申请人提供）：食物摄入和能量平衡受压力的深刻影响，反之亦然。但是，这些作用的神经机制在很大程度上尚不清楚。该项目的长期目标是追求压力和食物/能量平衡相互作用的机制。更具体地说，该提议旨在了解高度可口的食物如何减轻压力。使用有限的可口食品摄入量的模型对这些机制进行了研究，在该模型中，可以免费获得食物和水的大鼠每天两次访问少量的蔗糖溶液或水作为对照。在该模型中，蔗糖大鼠减弱了下丘脑 - 垂体 - 肾上腺（HPA）轴对压力的反应，并减少了脑奖励区域的压力诱导的神经元激活。此外，对于HPA抑制作用，蔗糖的卡路里和其他产后后果既不足够也不需要，这表明大脑奖励区域可能会介导该反应。基底外侧杏仁核（BLA）是一个关键的大脑奖励区域，也涉及驱动压力反应。此外，BLA中的神经活性对于蔗糖减轻压力是必要的，并且在蔗糖摄入史上，与突触可塑性有关的基因在BLA中被上调。总体而言，这表明可口的食物可能会通过BLA中的突触重塑抑制应力反应。因此，当前的提案解决了可口的假设可引起BLA的突触重组。我们预测，蔗糖摄入会增加BLA抑制性张力，从而减少应力激发的输出。此外，我们假设BLA中增强的抑制性张力是由于向BLA内抑制性中间神经元的动力增加所致。该提案以两个具体目的检验了这一假设。第一个具体目的将检验以下假设：蔗糖摄入量以与增强BLA输出的抑制作用相一致的方式增加突触。该目标将采用解剖方法来识别和量化突触膜在蔗糖摄入后对BLA神经元上的突触。第二个具体目的将检验，假设蔗糖诱导的BLA突触重组是由PCREB的AMPA受体激活介导的。该目标将使用AMPA受体活性和CREB/PCREB表达的BLA内部阻断，以确定该信号通路是否介导蔗糖诱导的突触重组。 公共卫生相关性：在压力下，许多人会增加对高度可口（例如美味，高糖或高脂）食物的摄入量，大概是为了帮助自己平静或安慰自己。但是，这种行为可以增加体重，并有助于肥胖的发展。该项目旨在了解可口的食物如何采取行动来减少对压力的反应，从而洞悉消费这些食物的动机，并可能为预防和治疗肥胖提供新的策略。