Peripheral manifestation of brain inflammation: signaling mechanisms

脑炎症的外周表现：信号机制

基本信息

批准号：
10195319
负责人：
Qizhi Gong
金额：
$ 43.18万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10195319
关键词：
Acute Alzheimer disease detection Alzheimer&apos s Disease Alzheimer&apos s disease patient Anatomy Animal Disease Models Axon Brain Cell Survival Cell physiology Cells Clinical Communication Cytokine Signaling Data Deposition Development Diagnostic Disease Progression Early Diagnosis Encephalitis Environment Event Fingerprint Future Genetic Transcription Goals In Vitro Inflammation Inflammatory Injections Investigation Knowledge Modeling Molecular Molecular Motors Neurodegenerative Disorders Neuronal Differentiation Neuropathy Olfactory Epithelium Olfactory Nerve Olfactory dysfunction Organ Pathogenesis Pathogenicity Pathway interactions Peripheral Physiological Physiology Presynaptic Terminals Process Senile Plaques Signal Transduction Site Supporting Cell System Techniques Testing Tissues Toxic effect Transportation Wild Type Mouse cytokine in vitro Model in vivo insight neuroinflammation neuropathology neurotrophic factor olfactory bulb olfactory sensory neurons response retrograde transport sensory system transcriptome sequencing

项目摘要

PROJECT SUMMARY Olfactory sensory neurons (OSNs), residing in olfactory epithelium (OE), send axon directly into olfactory bulb (OB) in the brain. This anatomical feature, unique among all sensory systems, exposes the brain directly to the environment. It is known that early stages of Alzheimer Disease (AD) are reflected in olfactory dysfunction. OB in the brain shows very early neuropathology in AD. It is well-established knowledge that AD progression is correlated with neuroinflammatory events in the brain, however, there is currently no reliable means for early detection of these events. Our preliminary data indicate that OE responds to increased levels of cytokines and pathogenic events in the OB, likely through retrograde signaling via the olfactory nerve. Retrograde signaling to trophic factors along axons from terminal to cell body is well known. We hypothesize that OE is a sensitive site to detect brain inflammation via retrograde inflammatory cytokine signaling through the olfactory nerve. To test this hypothesis, we will systematically characterize transcriptional changes in responding amyloid plaque induced inflammation. Signaling mechanisms will be investigated to gain understanding of critical cellular processes involved. The long-term goal of this study is to gain understanding of the molecular mechanisms of peripheral organ and brain communication of inflammation in neurodegenerative diseases.

项目概要嗅觉感觉神经元 (OSN) 位于嗅上皮 (OE) 中，将轴突直接发送到嗅球（OB）在大脑中。这种解剖学特征在所有感觉系统中都是独一无二的，它使大脑直接暴露于环境。众所周知，阿尔茨海默病（AD）的早期阶段表现为嗅觉功能障碍。产科大脑中的变化显示了 AD 中非常早期的神经病理学。众所周知，AD 的进展是与大脑中的神经炎症事件相关，然而，目前还没有可靠的方法来早期治疗检测这些事件。我们的初步数据表明，OE 对细胞因子水平的增加有反应，并且 OB 中的致病事件，可能是通过嗅觉神经的逆行信号传导。逆行信号发送至沿着轴突从末端到细胞体的营养因子是众所周知的。我们假设 OE 是一个敏感的通过嗅觉逆行炎症细胞因子信号传导检测脑部炎症的位点神经。为了检验这一假设，我们将系统地表征响应中的转录变化淀粉样斑块诱发炎症。将研究信号机制以了解涉及关键的细胞过程。这项研究的长期目标是了解分子神经退行性疾病中炎症的周围器官和大脑通讯机制。