Mechanisms of Inflammation-associated Taste Disorders

描述（由申请人提供）：味觉障碍，包括味觉扭曲和味觉丧失，与疾病、衰老和药物有关，并对厌食症、营养不良和抑郁症有重要影响。尽管最近在识别味觉受体和味觉信号蛋白方面取得了进展，但对味觉障碍的潜在机制知之甚少。我们的长期目标是阐明味觉功能障碍的分子和细胞基础。一些证据表明，炎症是味觉障碍发病的一个重要因素。首先，味觉异常通常与炎症有关，如感染和自身免疫性疾病。第二，炎症刺激可以改变味觉偏好和食物摄入。第三，味蕾细胞表达炎症因子的受体和信号分子。第四，我们已经证明炎症细胞因子，如干扰素，可以改变基因表达并诱导味蕾细胞死亡。然而，到目前为止，炎症如何影响味觉在很大程度上仍然未知。在这个应用中，我们建议在动物模型中研究炎症诱导的味觉障碍的机制。我们将追求以下具体目标：1)我们将研究急性和慢性炎症对味蕾细胞更新和周转的影响。2)我们将确定细胞因子在介导炎症对味蕾细胞更新和更新的影响中的作用。3)我们将研究炎症和细胞因子对味觉功能的影响。这些研究的结果将对理解炎症在味觉障碍中的作用具有重要意义，这将有助于制定新的治疗策略。此外，本研究将进一步加深我们对味蕾细胞更新调节机制的认识。

DESCRIPTION (provided by applicant): Taste disorders, including taste distortion and taste loss, are associated with diseases, aging, and medications and contribute significantly to anorexia, malnutrition, and depression. Despite recent progress in identifying taste receptors and taste signaling proteins, little is known about the underlying mechanisms of taste disorders. Our long-term objective is to elucidate the molecular and cellular basis of gustatory dysfunction. Several lines of evidence suggest that inflammation is an important contributing factor to the pathogenesis of taste disorders. First, taste abnormality is frequently associated with inflammatory conditions, such as infections and autoimmune diseases. Second, inflammatory stimuli can change taste preference and food intake. Third, taste bud cells express receptors and signaling molecules for inflammatory factors. Fourth, we have shown that inflammatory cytokines, such as interferons, can alter gene expression and induce cell death in taste buds. So far, however, how inflammation affects taste sensation remains largely unknown. In this application, we propose to study the mechanisms of inflammation-induced taste disorders in animal models. We are going to pursue the following specific aims: 1) We will study the effects of acute and chronic inflammation on taste bud cell renewal and turnover. 2) We will determine the roles of cytokines in mediating the effects of inflammation on taste bud cell renewal and turnover. 3) We will investigate the effects of inflammation and cytokines on taste function. Results from these studies will be important for understanding the roles of inflammation in taste disorders, which will be useful for developing new treatment strategies. In addition, this research will further our knowledge on the regulatory mechanisms of taste bud cell turnover.