科研之友
微信
新浪微博
Facebook
分享链接
摘要
Background: Molecular mechanisms underlying stress tolerance and vulnerability are incompletely understood. The fosB gene is an attractive candidate for regulating stress responses, because Delta FosB, an alternative splice product of the fosB gene, accumulates after repeated stress or antidepressant treatments. On the other hand, FosB, the other alternative splice product of the fosB gene, expresses more transiently than Delta FosB but exerts higher transcriptional activity. However, the functional differences of these two fosB products remain unclear.
Methods: We established various mouse lines carrying three different types of fosB allele, wild-type (fosB(+)), fosB-null (fosB(G)), and fosB(d) allele, which encodes Delta FosB but not FosB, and analyzed them in stress-related behavioral tests.
Results: Because fosB(+/d) mice show enhanced Delta FosB levels in the presence of FosB and fosB(d/d) mice show more enhanced Delta FosB levels in the absence of FosB, the function of FosB can be inferred from differences observed between these lines. The fosB(+/d) and fosB(d/d) mice showed increased locomotor activity and elevated Akt phosphorylation, whereas only fosB(+/d) mice showed antidepressive-like behaviors and increased E-cadherin expression in striatum compared with wild-type mice. In contrast, fosB-null mice showed increased depression-like behavior and lower E-cadherin expression.
Conclusions: These findings indicate that FosB is essential for stress tolerance mediated by Delta FosB. These data suggest that fosB gene products have a potential to regulate mood disorder-related behaviors.
- 出版日期2011-9-1
