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Publication : Alleviation of depression-like behavior in a cystic fibrosis mouse model by Hdac6 depletion.

First Author  Corey DA Year  2020
Journal  Sci Rep Volume  10
Issue  1 Pages  16278
PubMed ID  33004910 Mgi Jnum  J:297453
Mgi Id  MGI:6472407 Doi  10.1038/s41598-020-73298-4
Citation  Corey DA, et al. (2020) Alleviation of depression-like behavior in a cystic fibrosis mouse model by Hdac6 depletion. Sci Rep 10(1):16278
abstractText  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.
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