Activation of 5-HT4 receptors facilitates neurogenesis of injured enteric neurons at an anastomosis in the lower gut.

Activation of 5-HT4 receptors facilitates neurogenesis of injured enteric neurons at an anastomosis in the lower gut. J Smooth Muscle Res. 2015;51(0):82-94 Authors: Takaki M, Goto K, Kawahara I, Nabekura J Abstract Two-photon microscopy (2PM) can enable high-resolution deep imaging of thick tissue by exciting a fluorescent dye and protein at anastomotic sites in the mouse small intestine in vivo. We performed gut surgery and transplanted neural stem cells (NSC) from the embryonic central nervous system after marking them with the fluorescent cell linker, PKH26. We found that neurons differentiated from transplanted NSC (PKH [+]) and newborn enteric neurons differentiated from mobilized (host) NSC (YFP [+]) could be localized within the granulation tissue of anastomoses. A 5-HT4-receptor agonist, mosapride citrate (MOS), significantly increased the number of PKH (+) and YFP (+) neurons by 2.5-fold (P<0.005). The distribution patterns of PKH (+) neurons were similar to those of YFP (+) neurons. On the other hand, the 5-HT4-receptor antagonist, SB-207266 abolished these effects of MOS. These results indicate that neurogenesis from transplanted NSC is facilitated by activation of 5-HT4-receptors. Thus, a combination of drug administration and cell transplantation could be more beneficial than exclusive cell transplantation in treating Hirschsprung's disease and related disorders including post rectal cancer surgery. The underlying mec...
Source: Journal of Smooth Muscle Research - Category: Research Tags: J Smooth Muscle Res Source Type: research