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Modeling CO2-evoked fear in mice: role of acid-sensing ion channels

模拟二氧化碳引起的小鼠恐惧：酸敏感离子通道的作用

基本信息

批准号：
8414856
负责人：
John A Wemmie
金额：
$ 35.38万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-16 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8414856
关键词：
ASIC channel Acidosis Acids Address Americas Amygdaloid structure Animal Model Anxiety Anxiety Disorders Area Attenuated Behavior Behavioral Bicarbonates Biological Markers Brain Breathing Carbon Dioxide Cardiovascular system Chemicals Clinical Clinical Research Complex Data Fostering Freezing Fright Health Human Hydration status Invertebrates Kinetics Lead Mammals Mediating Microinjections Modeling Molecular Mus Neurobiology Neurons Neurotransmitters Panic Panic Attack Pathway interactions Patients Physiological Protons Research Role Signal Pathway Signal Transduction Signaling Molecule Site Structure Structure of terminal stria nuclei of preoptic region Symptoms Synapses Testing Therapeutic Transgenic Mice Translating Viral Vector carbonate dehydratase chemical reaction conditioned fear insight midbrain central gray substance novel novel therapeutics overexpression prevent receptor relating to nervous system research study response

项目摘要

DESCRIPTION (provided by applicant): Anxiety disorders are the most common form of psychiatric illness and exact a huge toll on America's health. Current treatments are often inadequate suggesting more effective, more specific therapies are needed. Clinical studies have firmly established that CO2 inhalation triggers anxiety and panic attacks, and that patients with anxiety disorders are hyper-responsive to CO2. These findings suggest that a better understanding of the molecular mechanisms underlying CO2 sensitivity could lead to novel insight into the causes of anxiety disorders and possibly lead to better treatments. Because CO2 sensitivity has been explored primarily in clinical studies, which are restricted in their ability to identify molecular mechanisms, there is a significant need for animal models to probe the mechanisms underlying CO2 sensitivity. In this proposal we address this need for animal models of CO2-evoked fear, by modeling CO2 behavioral and physiological responses in mice. We investigate the hypothesis that CO2 inhalation lowers brain pH, which activates pH-sensitive receptors in the fear circuit, which in turn increase the behavioral and physiological manifestations of fear, anxiety, and panic. This project may be critical for helping to explain the long recognized, but poorly understood clinical phenomenon of CO2 sensitivity. In addition, these studies are likely to have broader implications. Our preliminary data suggest that CO2 activates novel signaling pathways underlying anxiety disorders, and that these pathways might be therapeutically targeted to prevent anxiety disorders and reduce their symptoms.

描述（由申请人提供）：焦虑症是最常见的精神疾病，对美国人的健康造成了巨大的影响。目前的治疗方法往往不足，这表明需要更有效、更具体的治疗方法。临床研究已经确定，吸入二氧化碳会引发焦虑和恐慌发作，而患有焦虑症的患者对二氧化碳的反应非常敏感。这些发现表明，更好地了解二氧化碳敏感性的分子机制可能会导致对焦虑症原因的新见解，并可能导致更好的治疗方法。由于对二氧化碳敏感性的研究主要是在临床研究中进行的，这些研究在确定分子机制方面受到限制，因此迫切需要动物模型来探索二氧化碳敏感性的潜在机制。在本提案中，我们通过模拟小鼠的二氧化碳行为和生理反应来解决二氧化碳诱发恐惧的动物模型的需求。我们研究了二氧化碳吸入降低大脑pH值的假设，这激活了恐惧回路中的pH敏感受体，从而增加了恐惧、焦虑和恐慌的行为和生理表现。这个项目可能对帮助解释长期以来公认的，但知之甚少的二氧化碳敏感性临床现象至关重要。此外，这些研究可能会产生更广泛的影响。我们的初步数据表明，二氧化碳激活了焦虑障碍的新信号通路，这些通路可能是治疗目标，以预防焦虑障碍并减轻其症状。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Functional t1ρ imaging in panic disorder.

DOI：
10.1016/j.biopsych.2013.09.008
发表时间：
2014-06-01
期刊：
Biological psychiatry
影响因子：
10.6
作者：
Magnotta VA;Johnson CP;Follmer R;Wemmie JA
通讯作者：
Wemmie JA

Rapid acquisition strategy for functional T1ρ mapping of the brain.

大脑功能 T1ρ 映射的快速采集策略。

DOI：
10.1016/j.mri.2014.07.010
发表时间：
2014-11
期刊：
MAGNETIC RESONANCE IMAGING
影响因子：
2.5
作者：
Johnson, Casey P.;Heo, Hye-Young;Thedens, Daniel R.;Wemmie, John A.;Magnotta, Vincent A.
通讯作者：
Magnotta, Vincent A.

Localization and behaviors in null mice suggest that ASIC1 and ASIC2 modulate responses to aversive stimuli.

DOI：
10.1111/gbb.12108
发表时间：
2014-02
期刊：
Genes, brain, and behavior
影响因子：
0
作者：
Price MP;Gong H;Parsons MG;Kundert JR;Reznikov LR;Bernardinelli L;Chaloner K;Buchanan GF;Wemmie JA;Richerson GB;Cassell MD;Welsh MJ
通讯作者：
Welsh MJ

Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning.

DOI：
10.1111/j.1601-183x.2011.00683.x
发表时间：
2011-06
期刊：
Genes, brain, and behavior
影响因子：
0
作者：
Vralsted VC;Price MP;Du J;Schnizler M;Wunsch AM;Ziemann AE;Welsh MJ;Wemmie JA
通讯作者：
Wemmie JA

Neurobiology of panic and pH chemosensation in the brain.

大脑中恐慌和 pH 化学感觉的神经生物学。