Neurotrophin Regulation of Taste System Development

神经营养素对味觉系统发育的调节

• 批准号: 8468035
• 负责人: Robin Frances Krimm
• 金额: $ 36.47万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8468035
• 关键词: Adult; Attention; Birth; Brain-Derived Neurotrophic Factor; Cell Count; Chemicals; Development; Electrophysiology (science); Embryo; Embryonic Development; Epithelium; Excision; Goals; Health; Homeostasis; Immunohistochemistry; Impairment; Individual; Lead; Location; Mus; National Institute on Deafness and Other Communication Disorders; Nerve; Neurons; Oral cavity; Pattern; Peripheral; Peripheral Nervous System Diseases; Persons; Physiological; Process; Quality of life; Recovery; Regulation; Research; Sensory; Signaling Molecule; Specificity; Stimulus; Structure of geniculate ganglion; System; Systems Development; Taste Buds; Taste Disorders; Taste Perception; Testing; Therapeutic; Therapeutic Uses; Tongue; Transgenic Mice; Visit; behavior test; chorda tympani; critical period; design; meetings; nerve supply; neurotrophic factor; overexpression; postnatal; preference; public health relevance; research study; response

DESCRIPTION (provided by applicant): During development, gustatory innervation is a tightly regulated process in which specific numbers of primary taste afferents project to discrete regions of the oral cavity. Brain-derived neurotrophic factor (BDNF) regulates both the number and location of gustatory innervation during embryonic development. Our current research is designed to determine if and/or how these connections are important for central gustatory development or taste function and whether BDNF regulates development of the postnatal taste system. The proposed studies combine cell counting, tract tracing, immunohistochemistry, electrophysiology, and behavioral testing in conditional and inducible transgenic mice to: 1) determine if BDNF influences postnatal changes in geniculate ganglion and taste bud development, 2) determine if embryonic or postnatal BDNF is important for central terminal field organization, and 3) determine if embryonic or postnatal BDNF is important for adult gustatory function. Together, these studies test the hypotheses that: 1) embryonic BDNF determines the number of neurons innervating a taste bud, and taste buds increase in size to meet that number postnatally. 2) CNS terminal field formation is regulated by BDNF and the specificity of peripheral connections. 3) Gustatory sensitivity is reduced but that the taste system still functions despite wide-scale reorganization. These studies will determine how early peripheral innervation patterns influence continued development and function of the taste system. In addition, we will determine whether BDNF is required for postnatal gustatory development. Because these experiments examine how neurotrophin regulation of sensory innervation influences continued development and adult function, this project has important implications for the potential therapeutic use of these powerful signaling molecules in re-establishing gustatory function following neuronal impairment.

描述（由申请人提供）：在发育过程中，味觉神经支配是一个严格调节的过程，其中特定数量的初级味觉传入投射到口腔的离散区域。脑源性神经营养因子（BDNF）在胚胎发育过程中调节味觉神经支配的数量和位置。我们目前的研究旨在确定这些连接是否和/或如何对中枢味觉发育或味觉功能重要，以及BDNF是否调节出生后味觉系统的发育。拟定的研究将联合收割机细胞计数、束示踪、免疫组织化学、电生理学和条件性和诱导性转基因小鼠的行为测试相结合，以：1）确定BDNF是否影响膝状神经节和味蕾发育的出生后变化，2）确定胚胎或出生后BDNF是否对中央终末场组织重要，和3）确定胚胎或出生后BDNF是否对成年味觉功能重要。这些研究共同验证了以下假设：1）胚胎BDNF决定了支配味蕾的神经元数量，味蕾在出生后会增加大小以满足该数量。2)CNS终末场的形成受BDNF和外周连接特异性的调节。3)味觉敏感度降低，但味觉系统仍然发挥作用，尽管大规模重组。这些研究将确定早期外周神经支配模式如何影响味觉系统的持续发育和功能。此外，我们将确定是否BDNF是必需的出生后味觉发展。由于这些实验研究了神经营养因子对感觉神经支配的调节如何影响持续发育和成人功能，因此该项目对这些强大的信号分子在神经元损伤后重建味觉功能的潜在治疗用途具有重要意义。