Browse

Reduced chronic restraint stress in mice overexpressing hyperactive proteasomes in the forebrain

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
Kim, Ji Hyeon; Kim, Ahbin; Yun, Yejin; Park, Seoyoung; Lee, Jung Hoon; Lee, Yong-Seok; Lee, Min Jae
Issue Date
2020-01-13
Publisher
BMC
Citation
Molecular Brain, 13(1):4
Keywords
ProteasomeGateChronic stressDepression-like behaviorOxidative stress
Abstract
While chronic restraint stress (CRS) results in depression-like behaviors possibly through oxidative stress in the brain, its molecular etiology and the development of therapeutic strategies remain elusive. Since oxidized proteins can be targeted by the ubiquitin-proteasome system, we investigated whether increased proteasome activity might affect the stress response in mice. Transgenic mice, expressing the N-terminally deleted version of α3 subunit (α3ΔN) of the proteasome, which has been shown to generate open-gated mutant proteasomes, in the forebrain were viable and fertile, but showed higher proteasome activity. After being challenged with CRS for 14 d, the mutant mice with hyperactive proteasomes showed significantly less immobility time in the forced swimming test compared with their wild-type littermates, suggesting that the α3ΔN transgenic mice are resistant to CRS. The accumulation of ER stress markers, such as polyubiquitin conjugates and phospho-IRE1α, was also significantly delayed in the hippocampus of the mutants. Notably, α3ΔN mice exhibited little deficits in other behavioral tasks, suggesting that stress resilience is likely due to the degradation of misfolded proteins by the open-gated proteasomes. These data strongly indicate that not only is the proteasome a critical modulator of stress response in vivo but also a possible therapeutic target for reducing chronic stress.
ISSN
1756-6606
Language
English
URI
https://doi.org/10.1186/s13041-020-0548-y

http://hdl.handle.net/10371/164921
Files in This Item:
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse