Palatable Food and Synaptic Plasticity

美味的食物和突触可塑性

基本信息

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
项目类别：
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

项目摘要

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深受压力影响，反之亦然。然而，这些效应背后的神经机制在很大程度上尚不清楚。该项目的长期目标是探索压力和食物/能量平衡相互作用的机制。更具体地说，该提案旨在了解美味的食物如何缓解压力。这些机制是使用有限的可口食物摄入模型进行研究的，其中可以自由获取食物和水的大鼠每天两次额外获取少量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，并减少了大脑奖励区域中压力诱导的神经元激活。此外，蔗糖的热量和其他摄入后后果对于 HPA 抑制既不充分也不必要，这表明大脑奖励区域可能介导这种反应。基底外侧杏仁核（BLA）是一个关键的大脑奖励区域，也与驱动压力反应有关。此外，BLA 中的神经活动对于蔗糖缓解压力是必要的，并且在有蔗糖摄入史后，BLA 中与突触可塑性相关的基因会上调。总的来说，这表明可口的食物可能通过 BLA 中的突触重塑来抑制压力反应。因此，当前的提案解决了可口食物导致 BLA 突触重组的假设。我们预测蔗糖摄入会增加 BLA 抑制张力，从而导致压力兴奋输出减少。此外，我们假设 BLA 中抑制张力的增强是由于 BLA 内抑制性中间神经元的驱动力增加所致。该提案通过两个具体目标测试了这一假设。第一个具体目标将检验以下假设：蔗糖摄入会以与增强 BLA 输出抑制一致的方式增加突触并置。这一目标将使用解剖学方法来识别和量化摄入蔗糖后 BLA 神经元上的突触并置。第二个具体目标将检验蔗糖诱导的 BLA 突触重组是由 pCREB 的 AMPA 受体激活介导的假设。该目标将利用 BLA 内对 AMPA 受体活性和 CREB/pCREB 表达的阻断来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，许多人会增加美味（例如美味、高糖或高脂肪）食物的摄入量，大概是为了帮助平静或安慰自己。然而，这种行为会增加体重并导致肥胖的发生。该项目旨在了解可口的食物如何减少对压力的反应，从而深入了解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。