Interactions of the Noradrenergic and Serotonergic Systems in Autoresuscitation

去甲肾上腺素能系统和血清素能系统在自动复苏中的相互作用

基本信息

  • 批准号:
    10812310
  • 负责人:
  • 金额:
    $ 7.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-15 至 2025-09-14
  • 项目状态:
    未结题

项目摘要

Project Summary/ Abstract The noradrenergic (NA) and serotonergic (5-HT) networks of the brainstem are highly regulated and necessary components of the respiratory homeostatic network. Dysfunction of these systems has been linked to many congenital respiratory disorders including Sudden Infant Death Syndrome (SIDS). SIDS is a leading cause of neonate death and is thought to occur, in part, by the failure of the neonate autoresuscitation reflex. Previous data have informed our understanding of how these systems modulate protective respiratory responses to life threatening challenges independently, but limited information is available on the potential interplay between these two key systems while previous studies lack a more finessed manipulation provided by our methodology. In the following aims, I will test the hypothesis that the 5-HT and NA systems are integrally linked in regulating the autoresuscitation reflex and that different combinations of 5-HT and NA perturbation and stimulation will result in additive positive and negative outcomes in autoresuscitation. Aim 1. Determine the separate and combined functional and cellular effects of serotonergic activation and noradrenergic inhibition on the autoresuscitation reflex and respiratory network dynamics in response to hypercapnic anoxia. Aim 2. Determine the effect of serotonergic inhibition and noradrenergic activation on the autoresuscitation reflex. Aim 3. Determine the effect of serotonergic inhibition and noradrenergic inhibition or serotonergic activation and noradrenergic activation on the autoresuscitation reflex. To test these aims, I will utilize compounded recombinase and effector lines to access and manipulate the activity of the 5-HT and NA systems. For example, the Pet1::Cre; F_hM4D line bred to a DBH_FLPo; P_hM3D line will produce mice that, upon clozapine-N-oxide (CNO) application, will concurrently excite the 5-HT system (Pet1::Cre + P_hM3D) while inhibiting the NA system (DBH_FLPo + F_hM4D). For functional characterizations, the mice will be challenged with repeated bouts of hypercapnic anoxia to test their autoresuscitation reflex. For network activity characterization, cFos staining will be carried out on brainstem tissue in mice that have been challenged with sublethal hypercapnic anoxic exposures after excitation or inhibition of the 5-HT or NA systems. Understanding if these systems are independently regulating autoresuscitation will provide valuable information for future therapeutic investigations. This study will progress the field by expanding our understanding of interplay between the 5-HT and NA systems in health and disease as well as informing on the use of intricate genetic manipulations in the study of these two key respiratory systems. This work will significantly advance our understanding of the neural networks involved in respiratory regulation and disease. The training plan and environment that accompany this proposal will provide a solid foundation for a transition to research independence. Training includes scientific and professional development courses, workshops, and seminars while the environment includes cutting edge technology and equipment with training offered in house at BCM.
项目摘要/摘要

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes.
中枢去甲肾上腺素能神经元中基于 Vglut2 的谷氨酸信号传导对于正常呼吸和化学感应反射是可有可无的。
  • DOI:
    10.1101/2023.04.16.535729
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Chang,Yuan;Lusk,Savannah;Chang,Andersen;Ward,ChristopherS;Ray,RussellS
  • 通讯作者:
    Ray,RussellS
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Savannah J Lusk其他文献

Savannah J Lusk的其他文献

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{{ truncateString('Savannah J Lusk', 18)}}的其他基金

Interactions of the Noradrenergic and Serotonergic Systems in Autoresuscitation
去甲肾上腺素能系统和血清素能系统在自动复苏中的相互作用
  • 批准号:
    10537397
  • 财政年份:
    2022
  • 资助金额:
    $ 7.63万
  • 项目类别:

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