FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by ΔFosB.

Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
Biological psychiatry (Impact Factor: 9.47). 06/2011; 70(5):487-95. DOI: 10.1016/j.biopsych.2011.04.021
Source: PubMed

ABSTRACT Molecular mechanisms underlying stress tolerance and vulnerability are incompletely understood. The fosB gene is an attractive candidate for regulating stress responses, because ΔFosB, 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 ΔFosB but exerts higher transcriptional activity. However, the functional differences of these two fosB products remain unclear.
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 ΔFosB but not FosB, and analyzed them in stress-related behavioral tests.
Because fosB(+/d) mice show enhanced ΔFosB levels in the presence of FosB and fosB(d/d) mice show more enhanced ΔFosB 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.
These findings indicate that FosB is essential for stress tolerance mediated by ΔFosB. These data suggest that fosB gene products have a potential to regulate mood disorder-related behaviors.

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Available from: Yusaku Nakabeppu, Jul 29, 2015
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    • "As a consequence, DeltaFosB have been viewed as a sustained molecular switch to mediate forms of long-lasting neural and behavioral plasticity. Interestingly, an elegant study using mouse lines expressing differentially FosB and DeltaFosB showed that FosB is essential for the enhancement of stress tolerance and also neutralizes the correlation between psychostimulant-induced locomotor sensitization and accumulation of DeltaFosB in the striatum (Ohnishi et al., 2011). Therefore, both proteins could play important roles in the experimental protocol used in the present study. "
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    • "DFosB is a stable transcription factor that has an essential role in long-term adaptive changes in the brain associated with diverse conditions, including stress resilience and antidepressant treatment. For example, its induction in nucleus accumbens (NAc), a brain reward region, after chronic social defeat stress occurs preferentially in resilient mice and contributes to a state of resilience (Ohnishi et al, 2011; Vialou et al, 2010). Likewise, its induction in NAc by antidepressants is required for the therapeutic-like effects of these drugs (Vialou et al, 2010). "
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