The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays multiple roles in the enteric, peripheral, and central nervous systems (CNS). Although its most prominent biological function is as a signal transmission messenger from pre- to postsynaptic neurons, other roles such as shaping brain development and regulating neurite growth have also been described. Here, we review the less well-studied role of 5-HT as a modulator of neurite growth. 5-HT has been shown to regulate neurite growth in multiple systems and species, including in the mammalian CNS. 5-HT predominantly appears to suppress neurite growth, but depending on the model system and 5-HT receptor subtype, in rare cases, it may promote neurite outgrowth and elongation. Failure of axon regeneration in the adult mammalian CNS is a major problem in multiple diseases, and understanding how 5-HT receptors signal opposing effects on neurite growth may lead to novel neuroregenerative therapies, by targeting either 5-HT receptors or their downstream signaling pathways.
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