Neurotrophins and Development of Baroreceptor Pathways.

神经营养素和压力感受器通路的发育。

• 批准号: 7842111
• 负责人: AGNIESZKA Z BALKOWIEC
• 金额: $ 17.43万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7842111
• 关键词: Action Potentials; Afferent Neurons; Affinity; Age; Animal Model; Base Sequence; Biological Assay; Brain Stem; Brain-Derived Neurotrophic Factor; Calcium; Calcium Channel; Cardiovascular system; Cell Culture Techniques; Characteristics; Data; Development; Electric Stimulation; Embryo; Enzyme-Linked Immunosorbent Assay; Future; Goals; Growth Factor; Homeostasis; In Situ; In Vitro; Laboratories; Light; Mediator of activation protein; Messenger RNA; Methods; Modeling; Modification; Molecular; Morphology; Nerve Growth Factor Receptors; Neurons; Neurotrophic Tyrosine Kinase Receptor Type 2; Nodose Ganglion; Nucleus solitarius; Oligonucleotide Probes; Pathogenesis; Pathway interactions; Pattern; Perinatal; Physiological; Potassium; Pressoreceptors; Property; Protein Tyrosine Kinase; Proteins; Publishing; Rattus; Reflex action; Reflex control; Regulation; Relative (related person); Research; Research Design; Research Infrastructure; Research Personnel; Resolution; Respiratory System; Rodent; Role; Sensory; Source; Staging; Sudden infant death syndrome; Synapses; Techniques; Testing; Tetrodotoxin; Time; Tissues; Visceral; Visceral Afferents; Work; base; developmental disease; extracellular; gastrointestinal system; improved; in vivo; innovation; instrumentation; neuronal excitability; neuronal patterning; neuroregulation; neurotrophic factor; novel; novel strategies; patch clamp; postnatal; postsynaptic; programs; protein expression; research study; respiratory; response; voltage; Action Potentials; Afferent Neurons; Affinity; Age; Animal Model; Base Sequence; Biological Assay; Brain Stem; Brain-Derived Neurotrophic Factor; Calcium; Calcium Channel; Cardiovascular system; Cell Culture Techniques; Characteristics; Data; Development; Electric Stimulation; Embryo; Enzyme-Linked Immunosorbent Assay; Future; Goals; Growth Factor; Homeostasis; In Situ; In Vitro; Laboratories; Light; Mediator of activation protein; Messenger RNA; Methods; Modeling; Modification; Molecular; Morphology; Nerve Growth Factor Receptors; Neurons; Neurotrophic Tyrosine Kinase Receptor Type 2; Nodose Ganglion; Nucleus solitarius; Oligonucleotide Probes; Pathogenesis; Pathway interactions; Pattern; Perinatal; Physiological; Potassium; Pressoreceptors; Property; Protein Tyrosine Kinase; Proteins; Publishing; Rattus; Reflex action; Reflex control; Regulation; Relative (related person); Research; Research Design; Research Infrastructure; Research Personnel; Resolution; Respiratory System; Rodent; Role; Sensory; Source; Staging; Sudden infant death syndrome; Synapses; Techniques; Testing; Tetrodotoxin; Time; Tissues; Visceral; Visceral Afferents; Work; base; developmental disease; extracellular; gastrointestinal system; improved; in vivo; innovation; instrumentation; neuronal excitability; neuronal patterning; neuroregulation; neurotrophic factor; novel; novel strategies; patch clamp; postnatal; postsynaptic; programs; protein expression; research study; respiratory; response; voltage

DESCRIPTION (provided by applicant): Visceral sensory pathways that innervate the cardiovascular, respiratory and gastrointestinal systems are critical for reflex control of autonomic homeostasis. It is well established that functional characteristics of visceral reflexes, including arterial baro- and chemoreflexes, changes dramatically during perinatal development. However, the cellular mechanisms underlying the functional maturation of visceral reflexes are largely unknown. The leading hypothesis of this proposal is that the neurotrophin Brain-Derived Neurotrophic Factor (BDNF), released from the central terminals of visceral sensory afferents, regulates the activity-dependent maturation of postsynaptic target neurons. This hypothesis, supported by our recently published data and preliminary studies, will be tested using nodose ganglion primary and second-order sensory neurons, as well as functionally homogenous primary and second-order neurons in the aortic baroreceptor pathway, as a model. The proposed studies will utilize several innovative techniques, uniquely suited for studies of this kind, to characterize: 1) developmental regulation of activity-dependent expression of BDNF in nodose ganglion primary sensory neurons in general, and baroreceptor afferents in particular, and 2) electrophysiological and morphological effects of BDNF on second-order sensory neurons, including baroreceptor-relay neurons, from the developing nucleus tractus solitarius (NTS). A novel combination of electrical field stimulation with a highly sensitive, modified ELISA in situ, will be used to characterize changes in BDNF protein content in response to patterns of stimulation that mimic the physiological activity of baroreceptor afferents. Revealing the cellular mechanisms of BDNF regulation in visceral primary sensory neurons is a key to understanding BDNF role in visceral sensory pathways. A second part of the proposed work will analyze BDNF effects on voltage-activated potassium currents and dendritic morphology in specifically identified postsynaptic targets of BDNF-containing visceral sensory neurons and baroreceptor afferents. Results of these studies will provide new information fundamental to our understanding of basic mechanisms that govern development of sensory pathways. Moreover, by using the arterial baroreceptor pathway as a model, the proposed studies are relevant to understanding pathogenesis of developmental disorders of the cardio-respiratory system, such as Sudden Infant Death Syndrome (SIDS).

描述（由申请人提供）：支配心血管，呼吸系统和胃肠道系统的内脏感觉途径对于自主稳态的反射控制至关重要。 众所周知，内脏反射的功能特征（包括动脉巴罗和化学反射）在围产期发育过程中发生了巨大变化。 但是，内脏反射功能成熟的基础的细胞机制在很大程度上未知。 该提议的主要假设是，从内脏感觉传入的中央末端释放的神经营养蛋白脑衍生的神经营养因子（BDNF）调节了突触后靶神经元的活性成熟。 这一假设由我们最近发表的数据和初步研究支持，将使用Nodose神经节原发性和二阶感觉神经元，以及在主动脉baroreceptor途径中功能均匀的原发性和二阶神经元进行检验。 The proposed studies will utilize several innovative techniques, uniquely suited for studies of this kind, to characterize: 1) developmental regulation of activity-dependent expression of BDNF in nodose ganglion primary sensory neurons in general, and baroreceptor afferents in particular, and 2) electrophysiological and morphological effects of BDNF on second-order sensory neurons, including baroreceptor-relay neurons, from发育中的核片Solitarius（NTS）。 电场刺激与高度敏感，改良的ELISA原位的新型组合将用于表征BDNF蛋白含量的变化，以响应模仿压力受体传入的生理活性的刺激模式。 揭示内脏原发性感觉神经元中BDNF调节的细胞机制是了解内脏感觉途径中BDNF作用的关键。 拟议的工作的第二部分将分析BDNF对电压激活的钾电流和树突形态的影响，并在特定鉴定的含有BDNF的内脏感觉神经元和压力感受器传入的突触后靶靶标中进行了影响。 这些研究的结果将为我们理解控制感觉途径发展的基本机制提供新的信息。 此外，通过将动脉压力感受器途径作为模型，拟议的研究与理解心脏呼吸系统发育障碍的发病机理有关，例如猝死综合征（SIDS）。