This is based on Dr. Wang's Ph.D. thesis. When she graduated in 2020, it had not been published. At that time, they found that Per1 knockdown in the CA1 region produced depression-like behaviors, whereas Per2 knockdown in CA1 produced the opposite effect. However, it was difficult to integrate these findings into a coherent story. However, based on Wang's paper entitled "The Crosstalk between CREB and PER2 Mediates the Transition between Mania- and Depression-like Behavior" after graduation, she was able to interpret this investigation. Previously, she found that Per1 CRE knockout mice showed increased PER2 levels in CA1, and she proposed that this might be due to increased pCREB binding to the Per2 promoter, upregulating PER2 expression in CA1 and resulting in a depression-like phenotype similar to that caused by Per2 overexpression in CA1. She then used ChIP-qPCR and validated increased pCREB binding to the Per2 promoter. Furthermore, Per2 overexpression in CA1 was shown to be bipolar-like in her previous publication; therefore, she deduced that these Per1 CRE knockout mice might also be bipolar-like. Inspired by the reviewers of the Journal of Pineal Research, she designed an experiment to test the response of Per1 CRE knockout mice to a mood stabilizer and she found that they were partially rescued by lithium. Thus, the CRE sequence in the Per1 promoter may be a critical molecular link to the pathophysiology of bipolar depression.
When this paper was accepted, Dr. Wang jumped like a child, because no one knew what she had experienced during the five years after her Ph.D. graduation. Throughout those years, no matter what difficulties arose, she never lost hope, as she believed that everything would be solved step by step. Like a farmer planting crops, you need to water the plants, give them great patience and care, and most importantly, bear and wait—wait for the day when they will harvest. Finally, through her continuous work, even after graduation, she was able to resolve the issue.
Although this paper came late, the finding is a big surprise, for her, this is just the beginning of her scientific career. This teaches her to be patient in the pursuit of success. Every success requires persistence and steady effort. And she would like to express heartfelt thanks to the reviewers, who provided her great advice to make the entire study more complete.