Virus-Mediated Overexpression of ETS-1 in the Ventral Hippocampus Counteracts Depression-Like Behaviors in Rats
ETS-1 is a transcription factor that is a member of the E26 transformation-specific (ETS) family. Galanin receptor 2 (GalR2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of GalR2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress (CMS) decreased the expression of both ETS-1 and GalR2 in the ventral hippocampus of rats. Meanwhile, we demonstrated that overexpression of ETS-1 increased the expression of GalR2 in primary hippocampal neurons. Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2) of GalR2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats, which might be mediated by increasing the level of GalR2 and its downstream p-ERK1/2 in the ventral hippocampus.
KeywordsGalR2 ETS-1 Depression Chronic mild stress
This work was supported by grants from the National Natural Science Foundation of China (31271154, 31171032, and 81671345), the Beijing Natural Science Foundation (7162016), the Special Project on Natural Chronic Non-infectious Diseases (2016YFC1307202), and the Beijing Municipal Science and Technology Commission (Z181100001518001).
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Kuteeva E, Hökfelt T, Wardi T, Ogren SO. Galanin, galanin receptor subtypes and depression-like behaviour. EXS 2010, 102:163–181.Google Scholar
- 13.Lu J, Liang J, Wang JR, Hu L, Tu Y, Guo JY. Acupuncture activates ERK-CREB pathway in rats exposed to chronic unpredictable mild stress. Evid Based Complement Alternat Med 2013, 2013:469765.Google Scholar
- 15.Maroulakou IG, Papas TS, Green JE. Differential expression of ets-1 and ets-2 proto-oncogenes during murine embryogenesis. Oncogene 1994, 9:1551–1565.Google Scholar
- 36.Kuteeva E, Wardi T, Lundström L, Sollenberg U, Langel U, Hökfelt T, et al. Differential role of galanin receptors in the regulation of depression-like behavior and monoamine/stress-related genes at the cell body level serotonergic transmission. Neuropsychopharmacology 2008, 33:2573–2585.CrossRefGoogle Scholar