Science News
from research organizations

Study of antidepressants reveals how treatment helps depression management

Date:
September 15, 2015
Source:
Hiroshima University
Summary:
Several different classes of antidepressants increase early growth responses in astrocytes, star-shaped glial cells, which could help develop new treatments, researchers have shown.
Share:
FULL STORY

Treatment of primary cultured astrocytes with amitriptyline activates matrix metalloproteinases (MMPs) and receptor tyrosine kinases (RTKs, i.e., fibroblast growth factor receptor [FGFR] and epidermal growth factor receptor [EGFR]). Activated RTKs increase the mRNA and protein expression of EGR1, which in turn increases FGF2 mRNA expression.
Credit: Hiroshima University

Researchers in Japan have shown that several different classes of antidepressants increase early growth responses in astrocytes, star-shaped glial cells, which could help develop new treatments.

Amitriptyline is a prototypical antidepressant that is currently used worldwide. Generally, effects of antidepressants such as amitriptyline in depressive patients become evident after treatment for a few weeks. However, no study has investigated the reasons why effects are not immediately evident.

Previous studies have shown that amitriptyline increases the mRNA expression of fibroblast growth factor 2 (FGF2) in rat astrocytes, not neurons, slowly over 24 hours. However, the cellular mechanism that leads to the expression of FGF2 following amitriptyline treatment remains unclear.

In this study, the research group treated rat primary cultured astrocytes with amitriptyline. They found that it results in the activation of receptor tyrosine kinases (RTK; fibroblast growth factor receptor [FGFR] and epidermal growth factor receptor [EGFR]), which in turn increased FGF2 mRNA expression.

Professor Yoshihiro Nakata at Hiroshima University and Dr Minoru Takebayashi at National Hospital Organization Kure Medical Center and Chugoku Cancer Center said, "activated RTK induces the phosphorylation of extracellular signal-regulated kinase 1/2 and increases EGR1 mRNA and protein expression followed by FGF2 mRNA expression."

Professor Nakata said, "the current findings expand previous findings, in that the transcription factor EGR1 could be the de novo synthesized protein that is necessary for increasing FGF2 mRNA expression evoked by amitriptyline treatment."

The amitriptyline-induced signaling cascade is essential for the expression of FGF2 mRNA in primary cultured astrocytes. This cascade could be used to guide the development of antidepressants with novel mechanisms.


Story Source:

Materials provided by Hiroshima University. Note: Content may be edited for style and length.


Journal Reference:

  1. Naoto Kajitani, Kazue Hisaoka-Nakashima, Mami Okada-Tsuchioka, Mayu Hosoi, Toshiki Yokoe, Norimitsu Morioka, Yoshihiro Nakata, Minoru Takebayashi. Fibroblast growth factor 2 mRNA expression evoked by amitriptyline involves extracellular signal-regulated kinase-dependent early growth response 1 production in rat primary cultured astrocytes. Journal of Neurochemistry, 2015; DOI: 10.1111/jnc.13247

Cite This Page:

Hiroshima University. "Study of antidepressants reveals how treatment helps depression management." ScienceDaily. ScienceDaily, 15 September 2015. <www.sciencedaily.com/releases/2015/09/150915090659.htm>.
Hiroshima University. (2015, September 15). Study of antidepressants reveals how treatment helps depression management. ScienceDaily. Retrieved May 28, 2017 from www.sciencedaily.com/releases/2015/09/150915090659.htm
Hiroshima University. "Study of antidepressants reveals how treatment helps depression management." ScienceDaily. www.sciencedaily.com/releases/2015/09/150915090659.htm (accessed May 28, 2017).

RELATED STORIES