Enteric co-innervation: peripheral modulation of peristalsis in the striated portion of the esophagus?

• Applicant: Professor Dr. Winfried Neuhuber
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 38458035

Striated muscle of the esophagus is innervated by both cholinergic vagal and nitrergic/peptidergic myenteric neurons, a pattern described as enteric co-innervation. Recent results point to an inhibitory modulation of vagally induced striated muscle contractions by nitrergic and galaninergic enteric co-innervating neurons. Thus, the esophageal phase of swallowing can be influenced by a peripheral mechanism. As we could show, enteric co-innervation is phylogenetically conserved from fish to human indicating its functional relevance. Using immunohistochemistry for serotonin and tyrosine hydroxylase, we could further demonstrate that also monoaminergic neurons are involved in co-innervation. However, the origin of these axons which are either serotonin-positive, tyrosine hydroxylase-positive or both, remains to be determined. Do they derive from enteric serotoninergic or dopaminergic neurons or are they even sympathetic postganglionic fibers which have taken up serotonin from extrinsic sources, e.g., thrombocytes? The latter would significantly challenge current ideas of swallowing control. Solving these issues is pivotal for understanding co-innervation and control of deglutition as well as pathogenesis of dysphagia in monoaminergic disorders, e.g., Parkinsons disease. Thus, this proposal is aimed at elucidating serotonin synthesis versus uptake in myenteric neurons of the esophagus, a possible dopaminergic nature of myenteric neurons and a possible sympathetic contribution to co-innervation of esophageal striated muscle using immunohistochemical, molecular biological and neuronal tracing methods.

• DFG Programme: Research Grants
• Participating Person: Privatdozent Dr. Jürgen Wörl