Chronic mild stress leads to anxiety-like behavior and decreased p70 S6K1 activity in the hippocampus of male mice
Major affective disorders are highly prevalent, however, current remedies are limited within their effectiveness as a result of lack of knowledge of underlying molecular mechanisms. Recent reports have proven that reduced activity of p70 S6 kinase 1 (S6K1), a downstream target from the mechanistic target of rapamycin complex 1 (mTORC1), is related to anxiety-like behavior both in humans and rodents. The objective of this research ended up being to investigate relationship between S6K1 and anxiety-like behavior following chronic mild stress (CMS) and drug-caused inhibition of S6K1. Following CMS, anxiety-like behavior was evaluated utilizing an open field (OF) and elevated plus maze (EPM) in adult male C57/Bl6 rodents. After behavior analysis, examples of the hippocampus were harvested for quantification of S6K1, S6 ribosomal protein, glycogen synthase kinase-3 ß (GSK3ß), and beta tubulin via western blot. Our results show CMS rodents exhibit anxiety-like behavior within the OF and EPM and reduced activity of S6K1 within the hippocampus (HPC). We measured phosphorylation amounts of GSK3ß and located that GSK3ß phosphorylation seemed to be reduced following CMS when compared with control rodents. In addition, medicinal inhibition of S6K1 with PF-4708671 in male rodents was sufficient to create anxiety-like behavior within the OF and EPM. These results further offer the significant role of S6K1 within the pathogenesis of tension and affective disorders.