Chronic Intermittent Hypoxia: Sympathetic and Intrinsic Cardiac GanglionicInnervation

慢性间歇性缺氧：交感神经和内在心脏神经节神经支配

• 批准号: 9516205
• 负责人: ZIXI Jack CHENG
• 金额: $ 43.12万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9516205
• 关键词: Address; Anatomy; Animals; Atlases; Baroreflex; Brain; Brain Stem; Cardiac; Cardiovascular Diseases; Cardiovascular system; Chronic; Development; Enrollment; Female; Functional disorder; Future; Ganglia; Goals; Heart; Heart Rate; Heart failure; Hypertension; Hypoxia; Impairment; Lead; Maps; Modeling; Molecular; Motor Neurons; Mus; Nature; Nerve; Neurons; Neuropathy; Patients; Peripheral; Physiological; Pressoreceptors; Prevention strategy; Rattus; Reflex action; Research; Schools; Science; Site; Sleep Apnea Syndromes; Structure of parasympathetic ganglion; Structure of stellate ganglion; Tachycardia; Techniques; autonomic nerve; dorsal motor nucleus; educational atmosphere; effective therapy; graduate student; heart function; heart innervation; male; nerve supply; neuromechanism; novel; nucleus ambiguus; programs; treatment strategy; undergraduate student

Chronic intermittent hypoxia (CIH), the hallmark of sleep-disordered breathing (SDB), induces many cardiovascular disorders as seen in SDB. Thus, CIH-exposed animals have been used as an effective model to study the neural mechanisms underlying SDB-induced cardiovascular dysfunctions. The prevailing hypothesis is that CIH unbalances autonomic control that leads to cardiovascular complications. However, the neural mechanisms underlying CIH-induced autonomic imbalance is poorly understood, which impedes the development of effective treatments. Our long-term goals are to understand the autonomic innervations' topographical organization within the heart and then to determine CIH-induced structural remodeling of this topographical innervation and functional imbalance of the autonomic control of the cardiovascular system. Since the autonomic interaction may occur in local cardiac circuitry, the objective of this proposal is to address six important questions using a combination of state-of-the art anatomical and physiological techniques:1) What is the topographical organization map of sympathetic innervation of the normal heart? 2) What is the topographical organization map of parasympathetic intrinsic cardiac ganglia (ICG) innervation of the normal heart? 3) How do sympathetic and parasympathetic nerves interact? The remaining questions can be addressed after we have answered the first three questions from the normal animals. These additional questions are: 4) Does CIH change sympathetic cardiac innervation and function? 5) Does CIH change ICG innervation and function? 6) Does CIH change sympathetic inhibition of parasympathetic control at the heart? Though effects of CIH on the central control have been extensively studied, CIH-induced autonomic peripheral changes have not been yet well defined. We hypothesize that CIH will remodel cardiac autonomic postganglionic innervation, as well as alter their functions and interaction in male and female mice. Specifically, in Aim 1, we will determine whether CIH will induce structural remodeling of sympathetic and ICG preganglionic neurons and their projections to cardiac targets. In Aim 2, we will examine whether CIH will alter sympathetic postganglionic and parasympathetic ICG control of the heart and their functional interaction within the heart. Successful completion of these aims will provide novel information about the autonomic nerve topographical organization map within the whole heart, and the effects of CIH on the imbalance of autonomic control of the heart. The autonomic topographical organization in the 3D heart model will contribute to a cardiac-brain atlas and anatomical basis for normal autonomic cardiac functions. If CIH does have a significant effect on sympathetic and ICG innervation and function, we will further study the cellular and molecular mechanisms of how CIH may induce structural and functional deficits in the brain-heart circuitry, which will eventually contribute to new prevention and treatment strategies. These studies will enhance an integrated research and educational environment for biomedical sciences at UCF.

慢性间歇性缺氧（CIH）是睡眠呼吸的标志（SDB），引起了许多 心血管疾病如SDB所示。因此，暴露于CIH的动物已被用作有效模型 研究SDB诱导的心血管功能障碍的神经机制。盛行 假设是CIH不平衡会导致心血管并发症的自主控制。 但是，CIH引起的自主性失衡的神经机制知之甚少，这是 阻碍了有效治疗的发展。我们的长期目标是了解自主神经 神经内心内部的地形组织，然后确定CIH诱导的结构 对这种地形神经的重塑和对自主控制的功能失衡 心血管系统。由于自主互动可能发生在当地心脏电路中，因此 该建议是通过最先进的解剖学和 生理技术：1）什么是什么 正常的心？ 2）什么是副交感神经内神经节的地形组织图（ICG） 正常心脏的神经？ 3）交感神经和副交感神经如何相互作用？其余 在我们回答普通动物的前三个问题之后，可以解决问题。这些 其他问题是：4）CIH会改变交感神经神经支配和功能吗？ 5）cih 更改ICG神经和功能？ 6）CIH会改变对副交感控制的交感神经抑制 心？尽管已广泛研究了CIH对中央控制的影响，但CIH诱导的自主神经 外围变化尚未得到很好的定义。我们假设CIH会改造心脏 自主神经后神经支配，并改变其在男性和 雌鼠。具体而言，在AIM 1中，我们将确定CIH是否会诱导结构重塑 交感神经和ICG前神经元及其对心脏靶标的预测。在AIM 2中，我们将检查 CIH是否会改变同情的后传感和副交感神经ICG对心脏及其的控制 心脏内的功能相互作用。这些目标的成功完成将提供新颖的信息 关于全心中的自主神经地形组织图以及CIH的影响 心脏自主控制的失衡。 3D心脏的自主地形组织 模型将有助于心脏 - 脑图和正常自主心功能的解剖基础。如果 CIH确实对交感神经和ICG神经和功能有重大影响，我们将进一步研究 CIH如何在脑心脏中诱导结构和功能缺陷的细胞和分子机制 电路最终将有助于新的预防和治疗策略。这些研究会 增强UCF生物医学科学的综合研究和教育环境。

项目成果

Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis.

• DOI: 10.1038/s41598-023-27727-9
• 发表时间: 2023-04-07
• 期刊: Scientific reports
• 影响因子: 4.6

Topographical distribution and morphology of SP-IR axons in the antrum, pylorus, and duodenum of mice.

• DOI: 10.1016/j.autneu.2023.103074
• 发表时间: 2023-05
• 期刊: AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
• 影响因子: 2.7
• 作者: Mistareehi, Anas;Bendowski, Kohlton T.;Bizanti, Ariege;Madas, Jazune;Zhang, Yuanyuan;Kwiat, Andrew M.;Nguyen, Duyen;Kogut, Nicole;Ma, Jichao;Chen, Jin;Cheng, Zixi (Jack)
• 通讯作者: Cheng, Zixi (Jack)

Spinal afferent innervation in flat-mounts of the rat stomach: anterograde tracing.

• DOI: 10.1038/s41598-023-43120-y
• 发表时间: 2023-10-18
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Ma, Jichao;Duyen Nguyen;Madas, Jazune;Kwiat, Andrew M.;Toledo, Zulema;Bizanti, Ariege;Kogut, Nicole;Mistareehi, Anas;Bendowski, Kohlton;Zhang, Yuanyuan;Chen, Jin;Li, De-Pei;Powley, Terry L.;Furness, John B.;Cheng, Zixi
• 通讯作者: Cheng, Zixi