Role of chemokines in olfactory neurogenesis

神经细胞的再生是在人的一生中进行的，并受到不同因素的影响。中枢神经系统的神经发生增加，特别是由于损伤，例如中风的结果。然而，再生通常是不够的，在许多情况下需要长期的干扰。更好地了解潜在的生理过程对于治疗的具体改进是必不可少的。在成年哺乳动物的大脑中，神经发生的程度很低，而嗅觉上皮的特点是具有很高的再生能力，这种再生能力可以保存一生。嗅觉神经元异常再生能力的生理原因是该系统持续暴露于呼吸空气中的物质而易受伤害。这种高再生能力，加上不同相关细胞的明确定位和形态，使得再生过程的表征相对容易。趋化因子和趋化因子受体是中枢神经系统损伤后再生中起重要作用的信号系统。趋化因子CXC配体12 （CXCL12或SDF-1）及其受体CXCR4和CXCR7在损伤中枢神经系统的再生中起重要作用。通过遗传学、药理学、解剖学和生理学的具体结合，我们希望系统地研究CXCL12及其受体在小鼠嗅上皮感觉神经元中的作用。本项目旨在为CXCL12和g蛋白偶联受体CXCR4和CXCR7组成的趋化因子信号系统在成体神经发生中的功能提供新的信息，并有助于了解嗅觉系统与中枢神经系统其他神经发生区域在可塑性方面的差异。

The regeneration of nerve cells happens during the whole life and is adjusted by different influences. Neurogenesis in the central nervous system is increased in particular by injuries, e. g. as a result of a stroke. Nevertheless, the regeneration is usually insufficient what entails in many cases to long-term interferences. A better understanding of the underlying physiological processes is indispensable for the specific improvement of the treatment. In the brain of an adult mammal neurogenesis takes place only in low extent, the olfactory epithelium distinguishes itself by a high regeneration ability which is preserved the whole life through. The physiological reason for the unusual regeneration ability of the olfactory neurons is the vulnerabiliy of the system which is continuously exposed to substances in the breath air. This high capacity for regeneration, together with the clear localization and morphology of the different involved cells allows for relatively easy characterization of regeneration processes. A signal system which plays an important role for the regeneration after injuries in the central nervous system are chemokines and chemokine receptors. The chemokine CXC ligand 12 (CXCL12 or SDF-1) and his receptors CXCR4 and CXCR7 play important roles for the regeneration of the injured central nervous system. By specific combination of genetic, pharmacological, anatomical and physiological approaches we would like to systematically examine the role of CXCL12 and its receptors in sensory neurons of the olfactory epithelium of the mouse. This project should compile new information about the function of the chemokine signaling system consisting of CXCL12 and the G-protein coupled receptors CXCR4 and CXCR7 for neurogenesis in the adult organism, and help to understand the differences in plasticity of the olfactory system compared to other neurogenic regions of the central nervous system.