title: GDNF induces synaptic vesicle markers in enteric neurons.
abstract: Regulation of intestinal motility depends on an intact synaptic vesicle apparatus. Thus, we investigated the expression of the synaptic vesicle markers synaptophysin and synaptobrevin in the human enteric nervous system (ENS) and their regulation by glial cell line-derived neurotrophic factor (GDNF) in cultured enteric neurons. Full-thickness specimens of the human colon were assessed for expression of synaptophysin and synaptobrevin and neuronal localization was assessed by dual-label immunocytochemistry with PGP 9.5. Effects of GDNF on both synaptic markers were monitored in enteric nerve cell cultures and the presence of varicosities was determined by applying electron microscopy to the cultures. Human colonic specimens showed immunoreactivity for synaptophysin and synaptobrevin in both myenteric and submucosal ganglia as well as in nerve fibers. Both synaptic vesicle markers co-localized with the neuronal marker PGP 9.5 and exhibited granular accumulation patterns in the human and rat ENS. In cultured rat myenteric neurons GDNF treatment promoted expression of both synaptic vesicle markers and the formation of neuronal varicosities. The regulation of synaptophysin and synaptobrevin in enteric neurons by GDNF argues for the induction of functional neuronal networks in culture characterized by an increase of synaptogenesis.
authors.affiliation: Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany. Electronic address: m.boettner@anat.uni-kiel.de.
authors.forename: M
authors.initials: M
authors.lastname: Böttner
authors.forename: J
authors.initials: J
authors.lastname: Harde
authors.forename: M
authors.initials: M
authors.lastname: Barrenschee
authors.forename: I
authors.initials: I
authors.lastname: Hellwig
authors.forename: I
authors.initials: I
authors.lastname: Vogel
authors.forename: M
authors.initials: M
authors.lastname: Ebsen
authors.forename: T
authors.initials: T
authors.lastname: Wedel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D050683:R-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D050683:R-SNARE Proteins; D016708:Synaptophysin
keywords: BDNF; CM; CNS; Cell culture; ENS; Enteric nervous system; GDNF; GDNF family receptor; GFRα1; GI; LM; Localization; MP; Muc; N; RET; SMP; SNAP 25; SNARE; Synaptic plasticity; Synaptic vesicle; VAMP; brain derived neurotrophic factor; central nervous system; circular muscle layer; enteric nervous system; gastrointestinal; glial cell line-derived neurotrophic factor; longitudinal muscle layer; mRNA; mucosa; myenteric plexus; neuronal soma; qPCR; quantitative PCR; rearranged during transfection; soluble N-ethylmaleimide-sensitive-factor attachment receptor; submucosal plexus; synaptosome-associated protein 25kDa; vesicle associated membrane protein