Differential modulation of GR signaling and HDACs in the development of resilient/vulnerable phenotype and antidepressant-like response of vorinostat.

Autor: K V A; Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781125, Assam, India; Applied Biology Division, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Telangana, India., Wahul AB; Applied Biology Division, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Telangana, India., Soren K; Applied Biology Division, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Telangana, India., Das T; Applied Biology Division, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Telangana, India., Dey S; Applied Biology Division, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Telangana, India., Samudrala PK; Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781125, Assam, India., Kumar A; CSIR- Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500007, Telangana, India., Lahkar M; Department of Pharmacology, Gauhati Medical College, Guwahati 781032, Assam, India., Chakravarty S; Applied Biology Division, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Telangana, India. Electronic address: sumanachak@iict.res.in.
Jazyk: angličtina
Zdroj: Psychoneuroendocrinology [Psychoneuroendocrinology] 2021 Feb; Vol. 124, pp. 105083. Date of Electronic Publication: 2020 Dec 01.
DOI: 10.1016/j.psyneuen.2020.105083
Abstrakt: The present study explored the antidepressant potential of vorinostat (VOR) against chronic social defeat stress (CSDS) in mice. Since this model has the remarkable capacity to delineate the resilient and the defeated mice, we also looked for their molecular deviations. Defeated mice showed classical phenotypic alterations such as anhedonia, social avoidance, anxiety and despair. Whereas, resilient mice were immune to the development of those. Both defeated and resilient mice demonstrated marked CORT elevation in blood. Development of resilience vs. defeat to CSDS was found to be associated with the differential nuclear levels of GR, HDAC3 and HDAC6 in the hippocampus. Activation of a stress responsive adaptive mechanism involving these mediators at the nuclear level might be offering resilience while maladaptive mechanisms leading to defeat. Interestingly, an elevated hippocampal HDAC6 level in defeated mice was also observed, which was restored by VOR treatment. Further studies will be necessary to delineate the HDAC6 associated antidepressant mechanisms. As HDAC3 and HDAC6 are crucial mediators of GR signaling, further molecular studies may aid in understanding the basis of development of resilience to target MDD with new prospective.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: