How Antidepressants Activate Astrocytes

Researchers have uncovered the signalling pathway taken by antidepressants to increase the growth of astrocytes.

AsianScientist (Sep. 25, 2015) – Researchers in Japan have shown that several different classes of antidepressants increase early growth responses in star-shaped glial cells known as astrocytes. Their results, published in the Journal of Neurochemistry, suggest that promoting astrocyte growth could be a general mechanism to treat depression.

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, a research group led by Professor Yoshihiro Nakata at Hiroshima University and Dr. Minoru Takebayashi at National Hospital Organization Kure Medical Center and Chugoku Cancer Center, treated rat primary cultured astrocytes with amitriptyline.

They found that amitriptyline results in the activation of two receptor tyrosine kinases (fibroblast growth factor receptor [FGFR] and epidermal growth factor receptor [EGFR]), which in turn increased FGF2 mRNA expression.

“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,” Nakata said.

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.

The article can be found at: Kajitani et al. (2015) 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.

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Source: Hiroshima University.
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