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.

慢性间歇性低氧(CIH)是睡眠障碍呼吸(SDB)的标志，导致许多 如SDB中所见的心血管疾病。因此，CIH暴露动物已被用作一种有效的动物模型。 目的：研究SDB致心血管功能障碍的神经机制。盛行的 假说是脑出血导致自主神经控制失调，导致心血管并发症。 然而，CIH引起的自主神经失衡的神经机制尚不清楚。 阻碍了有效治疗方法的发展。我们的长期目标是了解自主神经 心脏内神经的局部组织，进而确定CIH诱导的结构 这种局部神经支配的重塑和自主神经控制的功能失衡 心血管系统。由于自主神经相互作用可能发生在局部心脏回路中，因此 这项建议是为了解决六个重要的问题，使用最先进的解剖和 生理技术：1)交感神经支配的地形图是什么？ 正常心脏？2)副交感神经心内神经节的地形图是什么？ 正常心脏的神经支配？3)交感神经和副交感神经如何相互作用？剩下的 问题可以在我们回答了正常动物的前三个问题后才能解决。这些 其他问题是：4)CIH是否改变了交感神经和心脏功能？5)CIH是否 改变了ICG的神经支配和功能？6)CIH是否改变了交感神经抑制在 心脏？虽然CIH对中枢控制的影响已被广泛研究，但CIH诱导的自主神经 外围国家的变化还没有得到很好的定义。我们假设CIH将重塑心脏 自主神经节后神经支配以及改变它们的功能和相互作用。 雌性老鼠。具体地说，在目标1中，我们将确定CIH是否会导致 交感和ICG节前神经元及其向心脏靶点的投射。在目标2中，我们将研究 脑出血是否会改变交感神经节后和副交感ICG对心脏的控制 心脏内的功能相互作用。这些目标的成功实现将提供新的信息 全心自主神经地形图及其对心脏功能的影响 心脏自主控制的失衡。3D心脏中的自主地形组织 该模型将有助于建立心脑图谱和正常自主心功能的解剖学基础。如果 脑出血对交感神经和ICG的神经支配和功能确实有显著影响，我们将进一步研究 CIH如何导致脑心结构和功能缺陷的细胞和分子机制 这最终将有助于新的预防和治疗战略。这些研究将 加强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