Expression and regulation of reelin and its receptors in the enteric nervous system

Background & aims: In the central nervous system (CNS), reelin coordinates migration and lamination of neurons and regulates synaptic plasticity, whereas its role in the enteric nervous system (ENS) remains enigmatic. Thus we determined the expression pattern and localization of reelin in the human ENS and monitored the time course of mRNA expression of the reelin signaling system in the rat intestine as well as in GDNF treated ENS cultures. Results: Reelin, its receptors and Dab1 were expressed in all intestinal layers as well as in isolated myenteric ganglia. Enteric ganglia and nerve fibers were immunoreactive for reelin which co-localized with PGP 9.5 and synaptophysin. In the rat small intestine, highest expression levels of reelin were detected at early postnatal stages. Enteric nerve cell cultures treated with GDNF showed marked up-regulation of reelin and its receptors. Conclusions: Reelin and its receptors are strongly expressed in the human ENS. Reelin is specifically localized in enteric neurons with highest expression levels during early postnatal life as well as in neuronal network forming enteric nerve cell cultures pointing to putative functions in the differentiation and maintenance of the ENS. Experimental methods: Gene expression of reelin, its receptors and Dab1 were analyzed in the human colon and isolated enteric ganglia. Co-localization of reelin with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin was studied by dual-label-immunocytochemistry. The time course of reelin expression was monitored in an ontogenetic study of rat intestines as well as in GDNF-treated cultures of enteric neurons. (C) 2014 Elsevier Inc All rights reserved.