GPR88在糖尿病性嗅觉功能障碍中的作用及机制研究

糖尿病性嗅觉功能障碍（ODD）严重影响患者生活质量，却未引起足够重视，且机制不清楚。课题组前期对ODD鼠嗅球组织通过RNA-Seq筛选出目前所知较少的G蛋白偶联受体88（GPR88）。结合既往研究表明GPR88与谷氨酸能传递密切相关，课题组前期也发现糖尿病组离子型谷氨酸受体（iGluR）水平发生显著改变，提示GPR88及iGluR参与ODD发生发展。我们提出：GPR88调控iGluR在ODD中的作用及机制研究的科学问题。项目拟综合运用行为学实验、组织学及分子生物学实验技术、借助转基因小鼠等，1）解析GPR88调控iGluR的机制；2）确定GPR88调控iGluR在ODD中的作用； 3）阐明GPR88 调控iGluR在ODD中的机制。项目若成功实施，我们将从分子、细胞与整体水平理解GPR88调控iGluR在ODD中的作用及分子机制，为ODD的发病机制提供新观点，为防治ODD提供新的潜在靶点。

Although olfactory dysfunction in diabetes (ODD) seriously affects the quality of life of patients, little attention has been paid to it and its underlying mechanism has remained elusive. Our preliminary data show that diabetic rats exhibited progressive olfactory dysfunction. Very strikingly, using the RNA-Seq technology, we observed that G protein-coupled receptor 88 (GPR88) expression was significantly altered in the olfactory bulb tissue of diabetic rats. Previous studies have shown that GPR88 is closely associated with glutamatergic transmission. In line with this, we obtained that the expression of ionotropic glutamate receptors (iGluRs) in the DM group was altered, suggesting that GPR88 and iGluRs were involved in the occurrence and development of ODD. Based on the above, our research group aims to decipher the roles and the underlying molecular and biochemical mechanisms of GPR88 and iGluRs in ODD. .To address such questions, my group adopts a multidisciplinary approach (behavioral study, histology techniques and molecular biology technology) based on GPR88 cKO mice and the Viral rescue of GPR88 expression in olfactory bulb neurons in GPR88 KO mice. This project aims to address the following issues: 1) the interaction between GPR88 and iGluR in olfactory bulb neuron; 2) the role of interaction GPR88 and iGluR in ODD; 3) the mechanism of the interaction between GPR88 and iGluR in ODD. Using a combination of molecular, cellular, and genetic approaches, we will answer the roles and molecular mechanism of GPR88 and iGluR signaling pathways in ODD at the molecular, cellular and animal levels. It is envisaged that the results derived from this study will help identify new therapeutic targets and with a new perspective about the pathogenesis of ODD. More importantly, the study is expected to provide a reliable theoretical basis for the prevention and treatment of ODD.