Impact of 5HT1A receptor subtype on adult neural stem cells derived from murine hippocampus

Adult neural stem cells (ANSC) have initially been isolated by Reynolds and Weiss. In our study we focused on the serotonergic system because of the crucial role of 5-HT in development. Tryptophan hydroxylase (TPH), the rate limiting enzyme of 5-HT synthesis could be detected immediately after fertilization in pronuclear stage zygotes. No other decisive enzyme for neurotransmitter synthesis has been detected at this early stage so far. 5-HT seems to exert a growth-modulating function within the CNS, but also in peripheral tissue. Here, we show that absence of 5-HT production by para-chlorophenylalanine mediated inhibition of TPH caused a dramatic drop in proliferation of ANSC, which was rescued by adding 5-HT to the media. Interestingly, 5-HT1A receptor blockade by the specific inhibitor WAY100635 counteracted the 5-HT rescue attempts, which led to the conclusion that absence of 5-HT influenced functional properties of adult stem cells, suggesting a link with the process of neurogenesis in-vivo. Our results regarding 5-HT1A receptor are in due accordance with another study showing that the effect of antidepressants up-regulating extra-cellular serotonin levels worked via the 5-HT1A receptor subtype and thus opening a link between our in-vitro system, neurogenesis and clinical relevance in terms of affective disorders.