Serotonin (5-hydroxytryptamine, 5-HT), a monoamine neurotransmitter, regulates neurological functions such as mood, sleep, and appetite. Erythropoietin (EPO) is well known for erythropoiesis but has recently emerged as a therapeutic agent in brain diseases. However, the mechanisms that induce EPO in the brain remain unclear. The present study was undertaken to investigate whether the effects of 5-HT involve EPO in murine hippocampal neurons. 5-HT produced a significant increase in neuronal differentiation of hippocampal neural progenitor cells. Expression of erythropoietin was increased in 5-HT-treated cells as well. The actions of 5-HT and EPO appeared to be similar in neurite outgrowth and spine formation. In addition, we show that hippocampal expression of EPO was decreased by chronic unpredictable stress (CUS) and that antidepressant treatment to maintain 5-HT concentration in synaptic cleft reversed this effect. In conclusion, actions of antidepressants might involve EPO induction in the brain.

Keywords: erythropoietin, depression, hippocampus