The crosstalk between CREB and PER2 mediates the transition between mania- and depression-like behavior
Published in Neuroscience and General & Internal Medicine
Bipolar disorder (BD) is a severe psychiatric disorder characterized by alternating manic and depressive episodes. The molecular mechanisms underlying the transition between mania and depression remain unclear. Utilizing a mania animal model induced by ouabain, we observed reduced phosphorylated level of cyclic AMP-responsive element-binding protein (pCREB) and Period (PER)2 expression in the cornu ammonis (CA1) region of the hippocampus, which were restored by lithium treatment. shRNA knockdown of CREB or Per2 in CA1 region induced mania-like behavior, while overexpression of both factors resulted in depression-like behavior. Furthermore, our protein analyses revealed that the upregulation or downregulation of CREB or Per2 influenced each other’s expression. Co-immunoprecipitation results demonstrated that CREB interacts with PER2. Taken together, our data suggest for potential inter-regulatory crosstalk between CREB–PER2 in hippocampal CA1 region, which mediates the transition between mania- and depression-like behaviors.
Dr. Xin-Ling Wang received her Bachelor's degree from Xi’an Jiaotong University in 2010. After obtaining her Master's degree in psychiatry from Zhejiang University in 2013 and her Ph.D. from the University of Chinese Academy of Sciences in 2020, she joined Shandong University as a Research Associate and continued her research on the role of circadian rhythm in mood disorders. Since 2023, she has been working as a postdoctoral researcher in Tsvetan Serchov’s team in CNRS and University of Freiburg. To date, she has revealed the molecular pathogenesis of mood transition between depression and mania and demonstrated the molecular switch underlying unipolar depression and bipolar depression. In recognition of this work, she received the 2025 Best Researcher in Neuroscience award.
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