Basic fibroblast growth factor increased glucocorticoid receptors in cortical neurons through MAP kinase pathway

Tadahiro Numakawa, Haruki Odaka, Naoki Adachi, Shuichi Chiba, Yoshiko Ooshima, Hitomi Matsuno, Shingo Nakajima, Aya Yoshimura, Kazuhiro Fumimoto, Yohei Hirai, Hiroshi Kunugi

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2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalNeurochemistry International
Volume118
DOIs
Publication statusPublished - 09-2018

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Numakawa, T., Odaka, H., Adachi, N., Chiba, S., Ooshima, Y., Matsuno, H., Nakajima, S., Yoshimura, A., Fumimoto, K., Hirai, Y., & Kunugi, H. (2018). Basic fibroblast growth factor increased glucocorticoid receptors in cortical neurons through MAP kinase pathway. Neurochemistry International, 118, 217-224. https://doi.org/10.1016/j.neuint.2018.06.009