Basic fibroblast growth factor increased glucocorticoid receptors in cortical neurons through MAP kinase pathway. (September 2018)

• Record Type: Journal Article
• Authors: Numakawa, Tadahiro; Odaka, Haruki; Adachi, Naoki; Chiba, Shuichi; Ooshima, Yoshiko; Matsuno, Hitomi; Nakajima, Shingo; Yoshimura, Aya; Fumimoto, Kazuhiro; Hirai, Yohei; Kunugi, Hiroshi
• Is Part Of: Neurochemistry international. Volume 118(2018)
• Page Start: 217
• Page End: 224
• Publication Date: 2018-09
• Subjects: Basic fibroblast growth factor -- Glucocorticoid receptor -- Mineralocorticoid receptor -- MAP kinase; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2018.06.009
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Prolonged and intense stress chronically increases blood concentration of glucocorticoids, which in turn causes downregulation of glucocorticoid receptor (GR) in the central nervous system (CNS). This process has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). Here, we found that basic fibroblast growth factor (bFGF) increased the expression of GR in the rat cerebral cortex and cultured cortical neurons and restored the reduced GR expression caused by glucocorticoid exposure. Among intracellular signaling pathways stimulated by bFGF, extracellular signal–regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway was responsible for the upregulation of GR. The bFGF-induced GR was functional as a transcription factor to enhance transcription of a target gene. Because high stress augments bFGF levels in the brain, it is likely that bFGF plays a compensating role for reduced GR expression after stress and thus should be studied as a therapeutic target for the treatment of MDD. Highlights: Basic FGF (bFGF) increased glucocorticoid receptor (GR) in cortical neurons. Mineralocorticoid receptor (MR) was also upregulated by bFGF. ERK/MAPK pathway was responsible only for the upregulation of GR. Increased GR was functional to enhance transcription of a target gene.