Department of Genetics and Genome Sciences, Case Western Reserve University, 833 BRB, 10900 Euclid Avenue, Cleveland, OH, 44106-4948, USA.
Sci Rep. 2020 Oct 1;10(1):16278. doi: 10.1038/s41598-020-73298-4.
Cystic fibrosis (CF) patients experience heightened levels of anxiety and depression. Stress from dealing with chronic disease and rigorous treatment regimens certainly are primary contributors to these outcomes. We previously have demonstrated that microtubule alterations in CF are linked to a number of CF phenotypes including growth regulation and inflammatory responses to airway bacterial challenge. Deletion of histone deactelyase 6 (HDAC6), a cytosolic deacetylase that regulates tubulin acetylation, in CF mice restores growth and inflammatory phenotypes to wild type (WT) profiles. In this study, the hypothesis that Hdac6 depletion in CF mice would impact behaviors since Hda6 inhibition has been previously reported to have anti-depressive properties. Data demonstrate that CF mice exhibit reduced activity and reduced open arm time in an elevated plus maze test which can be consistent with anxiety-like behavior. CF mice also exhibit depression-like behaviors compared to WT mice in an age dependent manner. By eight weeks of age, CF mice exhibit significantly more immobile time in the tail-suspension test, however, Hdac6 depletion reverses the depressive phenotype. These data demonstrate that loss of CFTR function may predispose patients to experience depression and that this behavior is Hdac6 dependent.
囊性纤维化 (CF) 患者会经历更高水平的焦虑和抑郁。应对慢性疾病和严格治疗方案的压力无疑是导致这些结果的主要因素。我们之前已经证明，CF 中的微管改变与许多 CF 表型有关，包括生长调节和对气道细菌挑战的炎症反应。CF 小鼠中组蛋白去乙酰化酶 6 (HDAC6) 的缺失（一种调节微管乙酰化的细胞质去乙酰化酶）可将生长和炎症表型恢复为野生型 (WT) 特征。在这项研究中，假设 CF 小鼠中的 Hdac6 耗竭会影响行为，因为先前已经报道 Hda6 抑制具有抗抑郁作用。数据表明，CF 小鼠在高架十字迷宫测试中表现出活动减少和开放臂时间减少，这与焦虑样行为一致。CF 小鼠还表现出与 WT 小鼠相比，以年龄依赖的方式表现出抑郁样行为。到 8 周龄时，CF 小鼠在尾部悬垂试验中表现出明显更多的不动时间，然而，Hdac6 耗竭逆转了抑郁表型。这些数据表明，CFTR 功能的丧失可能使患者易患抑郁症，并且这种行为是 Hdac6 依赖性的。
