PT  - JOURNAL ARTICLE
AU  - Min-Tsai Liu
AU  - Yung-Hui Kuan
AU  - Jingwen Wang
AU  - René Hen
AU  - Michael D. Gershon
TI  - 5-HT<sub>4</sub> Receptor-Mediated Neuroprotection and Neurogenesis in the Enteric Nervous System of Adult Mice
AID  - 10.1523/JNEUROSCI.1145-09.2009
DP  - 2009 Aug 05
TA  - The Journal of Neuroscience
PG  - 9683--9699
VI  - 29
IP  - 31
4099  - http://www.jneurosci.org/content/29/31/9683.short
4100  - http://www.jneurosci.org/content/29/31/9683.full
SO  - J. Neurosci.2009 Aug 05; 29
AB  - Although the mature enteric nervous system (ENS) has been shown to retain stem cells, enteric neurogenesis has not previously been demonstrated in adults. The relative number of enteric neurons in wild-type (WT) mice and those lacking 5-HT4 receptors [knock-out (KO)] was found to be similar at birth; however, the abundance of ENS neurons increased during the first 4 months after birth in WT but not KO littermates. Enteric neurons subsequently decreased in both WT and KO but at 12 months were significantly more numerous in WT. We tested the hypothesis that stimulation of the 5-HT4 receptor promotes enteric neuron survival and/or neurogenesis. In vitro, 5-HT4 agonists increased enteric neuronal development/survival, decreased apoptosis, and activated CREB (cAMP response element-binding protein). In vivo, in WT but not KO mice, 5-HT4 agonists induced bromodeoxyuridine incorporation into cells that expressed markers of neurons (HuC/D, doublecortin), neural precursors (Sox10, nestin, Phox2b), or stem cells (Musashi-1). This is the first demonstration of adult enteric neurogenesis; our results suggest that 5-HT4 receptors are required postnatally for ENS growth and maintenance.