title: SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF.
abstract: Control of intestinal motility requires an intact enteric neurotransmission. Synaptosomal-associated protein 25 (SNAP-25) is an essential component of the synaptic vesicle fusion machinery. The aim of the study was to investigate the localization and expression of SNAP-25 in the human intestine and cultured enteric neurons and to assess its regulation by the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF). SNAP-25 expression and distribution were analyzed in GDNF-stimulated enteric nerve cell cultures, and synaptic vesicles were evaluated by scanning and transmission electron microscopy. Human colonic specimens were processed for site-specific SNAP-25 gene expression analysis and SNAP-25 immunohistochemistry including dual-labeling with the pan-neuronal marker PGP 9.5. Additionally, gene expression levels and distributional patterns of SNAP-25 were analyzed in colonic specimens of patients with diverticular disease (DD). GDNF-treated enteric nerve cell cultures showed abundant expression of SNAP-25 and exhibited granular staining corresponding to synaptic vesicles. SNAP-25 gene expression was detected in all colonic layers and isolated myenteric ganglia. SNAP-25 co-localized with PGP 9.5 in submucosal and myenteric ganglia and intramuscular nerve fibers. In patients with DD, both SNAP-25 mRNA expression and immunoreactive profiles were decreased compared to controls. GDNF-induced growth and differentiation of cultured enteric neurons is paralleled by increased expression of SNAP-25 and formation of synaptic vesicles reflecting enhanced synaptogenesis. The expression of SNAP-25 within the human enteric nervous system and its downregulation in DD suggest an essential role in enteric neurotransmission and render SNAP-25 as a marker for impaired synaptic plasticity in enteric neuropathies underlying intestinal motility disorders.
authors: Institute of Anatomy, Christian-Albrechts-University of Kiel, Otto-Hahn-Platz 8, 24118, Kiel, Germany, m.barrenschee@anat.uni-kiel.de.
authors: M
authors: M
authors: Barrenschee
authors: M
authors: M
authors: Böttner
authors: J
authors: J
authors: Harde
authors: C
authors: C
authors: Lange
authors: F
authors: F
authors: Cossais
authors: M
authors: M
authors: Ebsen
authors: I
authors: I
authors: Vogel
authors: T
authors: T
authors: Wedel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002478:Cells, Cultured; D017615:Enteric Nervous System / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050825:Synaptosomal-Associated Protein 25 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25
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