AI Article Synopsis
- The study investigated the antidepressant effects of vorinostat (VOR) in mice experiencing chronic social defeat stress (CSDS), differentiating between resilient and defeated groups.
- Defeated mice exhibited symptoms like anhedonia, social avoidance, and anxiety, while resilient mice showed no such signs, despite both groups having elevated cortisol levels (CORT).
- Key differences in nuclear levels of GR, HDAC3, and HDAC6 in the hippocampus were linked to resilience and defeat; VOR treatment restored HDAC6 levels in defeated mice, suggesting potential pathways for new depression treatments.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.psyneuen.2020.105083 | DOI Listing |
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