Chronic administration of isotretinoin induces depressive- and anxiety-like behaviors by altering the neuroactive ligand-receptor interaction pathway in adolescent mice

作者：Yi Ren, Zhe Ren, Shuang Zhao, Wentao Wu, Jiaolin Wang, Fei He, Qi Zhong, Hanping Zhang, Jianjun Chen, Ke Xu, Peng Xie · 发表于：Translational Psychiatry · 年份：2025 · DOI：10.1038/s41398-025-03750-4 · 被引用次数：2 · 研究领域：Acne and Rosacea Treatments and Effects、Retinoids in leukemia and cellular processes、Arsenic contamination and mitigation

Clinical case reports have linked isotretinoin to depressive symptoms. As acne incidence peaks in adolescence, we focused on adolescent exposure. However, prior studies on isotretinoin's effects in adolescents have yielded inconsistent results, and direct mechanistic evidence remains scarce. Here, we analyzed depressive-like behaviors in adolescent mice treated with isotretinoin. Pathological changes in the prefrontal cortex and hippocampus of isotretinoin-treated mice were observed. We characterized the metabolic and gene-expression signatures of the hippocampus and prefrontal cortex in isotretinoin-treated mice using RNA sequencing and untargeted metabolomics. The results show that isotretinoin induced depressive- and anxiety-like behaviors and caused significant pathological changes in the hippocampus and prefrontal cortex. In the prefrontal cortex, two differentially expressed genes (Nmb and Pmch) within the neuroactive ligand-receptor interaction pathway correlated positively with depressive-like behaviors; in the hippocampus, two genes (Pomc and Gh) within the same pathway correlated with anxiety-like behaviors. Six differential metabolites associated with the neuroactive ligand-receptor interaction pathway - Adenosine (hippocampus); Tyramine, Taurine, N-acetylaspartylglutamic Acid (NAAG), and ADP (prefrontal cortex); and Taurine (serum) - were associated with depressive-like behaviors. Taurine in the prefrontal cortex was also associated with anxiety-like behaviors. Fi...