Microbiota and Neural Circuits controlling Social Behavior

控制社会行为的微生物群和神经回路

• 批准号: 9128233
• 负责人: Geert J. De Vries
• 金额: $ 22.68万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9128233
• 关键词: Address; Adolescent; Adult; Affect; Animal Model; Animals; Antibiotics; Anxiety; Area; Autistic Disorder; Bacteria; Behavior; Behavior Control; Birth; Brain; Child; Cognition; Communities; Data; Development; Disease; Eating Behavior; Emotional disorder; Emotions; Encephalitis; Etiology; Exposure to; Female; Food Additives; Foundations; Gastrointestinal tract structure; Germ-Free; Health; Human; Inflammatory disease of the intestine; Intestinal Diseases; Laboratories; Life; Link; Measures; Mental disorders; Metabolic syndrome; Microbe; Molecular; Mouse Strains; Mus; Neurodevelopmental Disorder; Neuropeptides; Oxytocin; Pain; Pathway interactions; Peptides; Phase; Physiology; Play; Probiotics; Program Development; Rodent; Role; Sex Characteristics; Signal Pathway; Social Behavior; Social Behavior Disorders; Stress; System; Testing; Vasopressins; Work; anxiety-related behavior; autistic children; base; brain behavior; early life exposure; emotional behavior; germ free condition; gut microbiome; gut microbiota; immune function; interest; male; microbial community; microbiome; microbiota; microorganism; mouse model; nerve supply; neural circuit; neurodevelopment; neuroregulation; novel; programs; public health relevance; relating to nervous system; research study; response; social; social anxiety; social communication

 DESCRIPTION (provided by applicant): Groundbreaking recent studies indicate that the community of microorganisms living in the digestive tract (the gut microbiota) plays a key role in psychiatric illnesses characterized by disordered emotional and social responses. Accelerated progress has also been made in understanding neural control of anxiety and social behavior, especially with regard to the roles of the `social neuropeptides,' vasopressin and oxytocin. To date nobody has linked these two exciting fields. Two established laboratories with complementary areas of expertise have joined forces to take on this task: one focused on sex differences in the brain and the neural basis of social behavior, the other on molecular pathways underlying the relationship between the microbiome and gut health. Together, these laboratories will develop mouse models to test the overall hypothesis that the gut microbiota acts early in life to permanently program vasopressin and oxytocin systems as well as anxiety- related and social behaviors controlled by these systems. In the first experiment, brain and behavior will be compared during development and in adulthood of germ-free mice after they have been colonized at birth by gut microbiota derived from either of two strains of mice that differ significantly in social and anxiety-related behaviors as well as composition of the microbiome. The second experiment takes advantage of a recent discovery in one of the two participating laboratories that commonly used food additives, i.e., emulsifiers, have surprisingly strong effects on physiology by acting on microbiota composition and its interaction with the host. Preliminary data suggest that these effects extend to the brain and behavior, which will be tested in the current project. Together, this project will address a crucial gap in our understanding of the gut-brain axis and its role in the development of anxiety-related and social behaviors, using physiologically relevant approaches. The findings will make possible subsequent identification of the specific microbiota affecting anxiety-related and social behaviors, and the signaling pathways involved. In addition, the payoff for studying effects of the microbiota on vasopressin and oxytocin expression will go beyond understanding microbiota effects on behavior, to include effects of the microbiota on autonomic functions, metabolic syndrome, and pain, all of which are affected by microbiota and modulated by these peptides.

 描述（由适用提供）：开创性的最新研究表明，生活在消化道（肠道微生物群）中的微生物社区在以情绪和社会反应为特征的精神病中起着关键作用。在理解焦虑和社会行为的神经控制方面，也取得了加速的进步，尤其是关于“社会神经肽”，加压素和催产素的作用。迄今为止，没有人链接这两个激动人心的领域。具有完整专业知识领域的两个知名实验室已经联合起来执行这项任务：一个专注于大脑的性别差异和社会行为的神经元基础，另一种是微生物组与肠道健康之间关系的分子途径。这些实验室将共同开发小鼠模型，以测试肠道菌群在生命早期起作用的总体假设 永久编程加压素和氧气相关的系统以及这些系统控制的与动画有关的和社会行为。在第一个实验中，在发育过程和无菌小鼠的成年期间，将比较大脑和行为，这些小鼠在出生时被肠道微生物群定植，这些小鼠的两种菌株中的任何一个在与社会和动画相关的行为以及微生物组的组成中都有明显不同。第二个实验利用了通常使用食品添加剂的两个参与实验室之一，即乳化剂，具有出人意料的强烈影响 在生理学上，作用于微生物群组成及其与宿主的相互作用。初步数据表明，这些影响扩展到大脑和行为，这将在当前项目中进行测试。共同，该项目将使用与身体相关的方法来解决我们对肠道轴及其在与焦虑有关和社会行为发展中的作用的关键差距。这些发现将使可能随后识别影响与焦虑有关的社会行为以及所涉及的信号通路的特定菌群。此外，研究微生物群对加压素和氧表达的影响的回报将超出理解微生物群对行为的影响，包括菌群对自主功能，代谢综合征和疼痛的影响，所有这些对这些肽的影响并受这些肽的调节。