Mice deficient for wild-type p53-induced phosphatase 1 display elevated anxiety- and depression-like behaviors

• This paper is the first to define a critical role of Wip1 in mood stabilization.
• The reduced Wip1 protein in the hippocampus of mice as a result of CUMS is restored by fluoxetine treatment.
• Wip1-deficient mice display impaired exploratory behaviors.
• Wip1-deficient mice display increased anxiety- and depression-like behaviors.

Mood disorders are a severe health burden but molecular mechanisms underlying mood dysfunction remain poorly understood. Here, we show that wild-type p53-induced phosphatase 1 (Wip1) negatively responds to the stress-induced negative mood-related behaviors. Specifically, we show that Wip1 protein but not its mRNA level was downregulated in the hippocampus but not in the neocortex after 4 weeks of chronic unpredictable mild stress (CUMS) in mice. Moreover, the CUMS-responsive WIP1 downregulation in the hippocampus was restored by chronic treatment of fluoxetine (i.p. 20 mg/kg) along with the CUMS procedure. In addition, Wip1 knockout mice displayed decreased exploratory behaviors as well as increased anxiety-like and depression-like behaviors in mice without impaired motor activities under the non-CUMS condition. Furthermore, the Wip1 deficiency-responsive anxiety-like but not depression-like behaviors were further elevated in mice under CUMS. Although limitations like male-alone sampling and multiply behavioral testing exist, the present study suggests a potential protective function of Wip1 in mood stabilization.

Figure optionsDownload high-quality image (170 K)Download as PowerPoint slide