| First Author | Ohnishi YN | Year | 2011 |
| Journal | Biol Psychiatry | Volume | 70 |
| Issue | 5 | Pages | 487-95 |
| PubMed ID | 21679928 | Mgi Jnum | J:220448 |
| Mgi Id | MGI:5634797 | Doi | 10.1016/j.biopsych.2011.04.021 |
| Citation | Ohnishi YN, et al. (2011) FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by DeltaFosB. Biol Psychiatry 70(5):487-95 |
| abstractText | BACKGROUND: Molecular mechanisms underlying stress tolerance and vulnerability are incompletely understood. The fosB gene is an attractive candidate for regulating stress responses, because DeltaFosB, 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 DeltaFosB 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 DeltaFosB but not FosB, and analyzed them in stress-related behavioral tests. RESULTS: Because fosB(+/d) mice show enhanced DeltaFosB levels in the presence of FosB and fosB(d/d) mice show more enhanced DeltaFosB 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 DeltaFosB. These data suggest that fosB gene products have a potential to regulate mood disorder-related behaviors. |
