The bFGF induced upregulation of both GR and MR levels
The bFGF-induced upregulation of both GR and MR levels observed in our study raises a question regarding whether the simultaneous augmentation of the two receptors has a physiological and/or medical significance. It has been suggested that MR stimulates intracellular signaling pathways to minimize stress-caused disturbances by regulating neuronal homeostasis, while GR signaling serves to support stress recovery (De Kloet and Derijk, 2004). In addition, physical stress acutely increases bFGF levels in several regions, including the prefrontal cortex and hippocampus of the rat VX-689 receptor (Bland et al., 2006, 2007). Treatment with corticosterone, the primary glucocorticoid in rodents, also has been shown to increase bFGF levels in the rat hippocampus and in cultured astrocytes (Molteni et al., 2001). Physically stressed rats also showed a reduced level of bFGF antisense RNA, which is transcribed from the antisense strand of the FGF-2 gene locus and contains a complementary sequence of 464 nucleotides encoding bFGF mRNA in the hippocampus via the action of corticosterone (Frank et al., 2007). Considering these results, including those of this study, stress-induced bFGF upregulation in the brain can play a significant role in coping with stress by preventing disturbances in neuronal homeostasis and accelerating the recovery phase by upregulating MR and GR expression, respectively. Therefore, bFGF and its signaling pathways are likely to be attractive therapeutic targets for the treatment of depression in humans.
Here, we demonstrated that bFGF activity had an ameliorating effect against the downregulation of GR expression in cortical neurons after glucocorticoid exposure. bFGF influences neural fate and functions throughout the CNS, from development to adult stages (Matsuda et al., 1990). Therefore, bFGF seems to critically determine survival and, proliferation in neural progenitor/stem cells (Temple and Qian, 1995 ). Revealing the action of glucocorticoids through GR and MR signaling that underlies the functions of bFGF in the CNS is an important challenge that we must tackle in order to further our understanding of the functional interaction between the endocrine system and CNS.
Conflicts of interest
Acknowledgments This project was supported by the the Strategic Research Program for Brain Sciences (10102837) by the Ministry of Education, Culture, Sports, Science and Technology of Japan (H.K.), the Intramural Research Grant (No. 24-11) for Neurological and Psychiatric Disorders of NCNP (H. K.), grants from the Grant-in-Aid for Scientific Research(C) (JSPS KAKENHI grant number: 16K06996, T.N.; 18K07891, N.A) in the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and also supported by grants from by Takeda Science Foundation (T.N. and N.A).