Wang Xin-Ling, Ji Yan-Bin, Li Su-Xia, Serchov Tsvetan
Department of Medical Psychology and Ethics, School of Basic Medical Sciences, Shandong University, Ji'nan, 250012, Shandong, China.
Centre National de La Recherche Scientifque (CNRS), Université de Strasbourg, Institut Des Neurosciences Cellulaires Et Intégratives (INCI) UPR 3212, 67000, Strasbourg, France.
Neuropsychopharmacology. 2025 Feb 27. doi: 10.1038/s41386-025-02076-5.
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.
双相情感障碍（BD）是一种严重的精神疾病，其特征为躁狂和抑郁发作交替出现。躁狂和抑郁之间转变的分子机制仍不清楚。利用哇巴因诱导的躁狂动物模型，我们观察到海马齿状回（CA1）区域中环状AMP反应元件结合蛋白（pCREB）的磷酸化水平降低以及周期蛋白（PER）2表达降低，而锂治疗可使其恢复。在CA1区域对CREB或Per2进行短发夹RNA敲低会诱导出类似躁狂的行为，而这两种因子的过表达则会导致类似抑郁的行为。此外，我们的蛋白质分析表明，CREB或Per2的上调或下调会相互影响彼此的表达。免疫共沉淀结果表明CREB与PER2相互作用。综上所述，我们的数据表明海马CA1区域中CREB - PER2之间可能存在潜在的相互调节的串扰，这介导了类似躁狂和类似抑郁行为之间的转变。
