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Archival Report| Volume 70, ISSUE 5, P487-495, September 01, 2011

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FosB Is Essential for the Enhancement of Stress Tolerance and Antagonizes Locomotor Sensitization by ΔFosB

  • Yoshinori N. Ohnishi
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York
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  • Yoko H. Ohnishi
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York
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  • Masaaki Hokama
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
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  • Hiroko Nomaru
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
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  • Katsuhisa Yamazaki
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
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  • Yohei Tominaga
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
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  • Kunihiko Sakumi
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
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  • Eric J. Nestler
    Affiliations
    Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York
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  • Yusaku Nakabeppu
    Correspondence
    Address correspondence to Yusaku Nakabeppu, D.Sc., Kyushu University, Medical Institute of Bioregulation, Department of Immunobiology and Neuroscience, Division of Neurofunctional Genomics, 3-1-1 Maidashi Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan
    Affiliations
    Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
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      Background

      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.

      Methods

      We established various mouse lines carrying three different types of fosB allele, wild-type (fosB+), fosB-null (fosBG), and fosBd allele, which encodes ΔFosB but not FosB, and analyzed them in stress-related behavioral tests.

      Results

      Because fosB+/d mice show enhanced ΔFosB levels in the presence of FosB and fosBd/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 fosBd/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 ΔFosB. These data suggest that fosB gene products have a potential to regulate mood disorder-related behaviors.

      Key Words

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      Linked Article

      • Erratum
        Biological PsychiatryVol. 72Issue 5
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          An error has been discovered in “FosB Is Essential for the Enhancement of Stress Tolerance and Antagonizes Locomotor Sensitization by ΔFosB” by Ohnishi et al. which appeared in Biological Psychiatry (2011;70:487–495). Specifically, the starting residue for the Δ1FosB protein should be 50 not 49 in Figure S1 (see page 7 of Supplement 1). All other information provided in the Supplement remains unchanged.
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