A study of antidepressants reveals how treatment helps depression management
News Sep 16, 2015
Researchers in Japan have shown that several different classes of antidepressants increase early growth responses in astrocytes, the 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, as depicted in the illustration above.
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.
Note: Material may have been edited for length and content. For further information, please contact the cited source.
Takebayashi M et al. 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, Published Online August 6 2015. doi: 10.1111/jnc.13247
Inter-areal Balanced Amplification Enhances Signal Propagation in the BrainNews
Neuroscientists find that signal transmission in a large-scale model of the primate brain is robust under the condition in which area-to-area connections exhibit a “balance” between excitation and inhibition.READ MORE
Early Life Experiences Alter DNA Structure in the Adult BrainNews
Scientists report in the journal Science that the type of mothering a female mouse provides her pups actually changes their DNA.READ MORE
Worms Exhibit Fear and Respond to Anti-anxiety MedsNews
A team of investigators has uncovered new clues about the mechanisms of fear and anxiety through an unlikely creature: the tiny nematode worm.READ MORE
Comments | 0 ADD COMMENT
International Conference on Neuroimmunology, Neurological disorders and Neurogenetics
Sep 26 - Sep 27, 2018