Peripheral manifestation of brain inflammation: signaling mechanisms

项目总结 摘要嗅觉神经元(OSNs)位于嗅觉上皮(OE)，将轴突直接送入嗅球。 (OB)在大脑中。这一解剖特征在所有感觉系统中都是独一无二的，它将大脑直接暴露在 环境。众所周知，阿尔茨海默病(AD)的早期表现为嗅觉障碍。OB 在大脑中显示了阿尔茨海默病的早期神经病理。众所周知，AD进展是 然而，与大脑中的神经炎性事件相关，目前还没有可靠的方法来早期 检测到这些事件。我们的初步数据表明，OE对增加的细胞因子和 OB中的致病事件，可能通过嗅神经逆行信号传递。逆行发送信号至 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是一个敏感的 通过嗅觉逆行炎症细胞因子信号检测脑部炎症的位置 很有胆量。为了验证这一假设，我们将系统地描述反应过程中转录变化的特征。 淀粉样斑块引起炎症。将研究信号机制以了解 涉及到关键的细胞过程。这项研究的长期目标是了解分子 神经退行性疾病炎症的外周器官和脑通讯机制。

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.