Probable involvement of p11 with interferon alpha induced depression

• Published in: Scientific reports 2016-01, Vol.6 (1), p.17029-17029, Article 17029
• Main Authors: Guo, Jiqiang, Zhang, Wen, Zhang, Lili, Ding, Huaxia, Zhang, Jingjing, Song, Chen, Zhang, Yanfei, Xia, Namei, Li, Mingfang, Liang, Yinming, Hu, Xianzhang, Luan, Haojiang, Wang, Hui
• Format: Article
• Language: English
• Subjects: 13/109; 13/21; 13/51; 13/89; 14/34; 631/378/87; 692/308/1892; 692/699/476/1414; Animals; Annexin A2 - genetics; Annexin A2 - metabolism; Blotting, Western; Calcium-binding protein; Cell Line, Tumor; Depression - chemically induced; Depression - metabolism; Dose-Response Relationship, Drug; Down-regulation; Down-Regulation - drug effects; Gyrus Cinguli - metabolism; Hippocampus - metabolism; Humanities and Social Sciences; Humans; Immobilization; Immunohistochemistry; Interferon; Interferon-alpha - adverse effects; Mental depression; Mice, Inbred BALB C; multidisciplinary; Neuroblasts; Overexpression; Receptor, Serotonin, 5-HT1B; Recombinant Proteins - adverse effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; S100 protein; S100 Proteins - genetics; S100 Proteins - metabolism; Science; Serotonin receptors; Side effects; Swimming; Tail; Time Factors; α-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep17029

Depression is one of the major side effects of interferon alpha (IFN-α) treatment, but the molecular mechanism underlying IFN-α-induced depression remains unclear. Several studies have shown that the serotonin receptors 5-HTR1b and 5-HTR4 play key roles in the anti-depression effects associated with p11 (S100A10). We investigated the effects of IFN-α on the regulation of p11, 5-HTR1b and 5-HTR4 in mice and human neuroblastoma cells (SH-sy5y). We found that intraperitoneal injection with IFN-α in Balb/c mice resulted in an increased immobility in FST and TST and potently lowered the protein levels of p11, 5-HTR1b and 5-HTR4 in the hippocampus or cingulate gyrus. IFN-α significantly down-regulated the protein levels of p11, 5-HTR1b and 5-HTR4 in SH-sy5y cells, in a time- and dose-dependent manner. Our study revealed that over-expression of p11 could prevent the IFN-α-induced down-regulation of 5-HTR1b and 5-HTR4. The results indicated that IFN-α treatment resulted in p11 down-regulation, which subsequently decreased 5-HTR1b and 5-HTR4 in vitro or in vivo . Our findings suggested that p11 might be a potential regulator on 5-HTR1b and 5-HTR4 as well as a predictor of or a therapeutic target for IFN-α-induced depression.