Peripheral manifestation of brain inflammation: signaling mechanisms

脑炎症的外周表现：信号机制

• 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
• 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' s Disease; Alzheimer' 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

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.

项目摘要 嗅感觉神经元（olfactory sensory neurons，OSNs）位于嗅上皮（olfactory epithelium，OE）内，将轴突直接传入嗅球 (OB)在大脑中。这一解剖学特征在所有感觉系统中是独一无二的，它使大脑直接暴露在 环境已知阿尔茨海默病（AD）的早期阶段反映在嗅觉功能障碍中。ob 显示了AD的早期神经病理学。众所周知，AD进展是 然而，目前还没有可靠的手段来早期检测与脑中神经炎症事件相关的神经系统炎症。 检测这些事件。我们的初步数据表明，OE响应于细胞因子水平的增加， OB中的致病事件，可能通过经由嗅觉神经的逆行信号传导。逆行信号， 营养因子沿着轴突从末端到细胞体是众所周知的。我们假设OE是一种敏感的 通过嗅觉的逆行炎症细胞因子信号传导检测脑炎症的位点 神经。为了验证这一假设，我们将系统地描述转录变化的反应， 淀粉样斑块诱导炎症。将研究信号机制，以了解 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外周器官和脑通讯机制。