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

Yoshinori N. Ohnishi, Yoko H. Ohnishi, Masaaki Hokama, Hiroko Nomaru, Katsuhisa Yamazaki, Yohei Tominaga, Sakumi Kunihiko, Eric J. Nestler, Yusaku Nakabeppu

Research output: Contribution to journalArticle

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Abstract

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 (fosB G), and fosB d 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 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. 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.

Original languageEnglish
Pages (from-to)487-495
Number of pages9
JournalBiological Psychiatry
Volume70
Issue number5
DOIs
Publication statusPublished - Sep 1 2011

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Cadherins
Genes
Alleles
Locomotion
Mood Disorders
Antidepressive Agents
Phosphorylation
Depression
Behavior Rating Scale

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

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FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by ΔfosB. / Ohnishi, Yoshinori N.; Ohnishi, Yoko H.; Hokama, Masaaki; Nomaru, Hiroko; Yamazaki, Katsuhisa; Tominaga, Yohei; Kunihiko, Sakumi; Nestler, Eric J.; Nakabeppu, Yusaku.

In: Biological Psychiatry, Vol. 70, No. 5, 01.09.2011, p. 487-495.

Research output: Contribution to journalArticle

Ohnishi, Yoshinori N. ; Ohnishi, Yoko H. ; Hokama, Masaaki ; Nomaru, Hiroko ; Yamazaki, Katsuhisa ; Tominaga, Yohei ; Kunihiko, Sakumi ; Nestler, Eric J. ; Nakabeppu, Yusaku. / FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by ΔfosB. In: Biological Psychiatry. 2011 ; Vol. 70, No. 5. pp. 487-495.
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abstract = "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 (fosB G), and fosB d 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 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. 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.",
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AU - Yamazaki, Katsuhisa

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