SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF
SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF
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DOI：
10.1007/s00418-015-1310-x
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发表时间：
2015-06-01
影响因子：
2.3
通讯作者：
Wedel, T.
中科院分区：
文献类型：
--
作者：
Barrenschee, M.;Boettner, M.;Wedel, T.
控制肠蠕动需要完整的肠神经传递。突触体相关蛋白25（SNAP-25）是突触囊泡融合机制的重要组成部分。本研究的目的是研究SNAP-25在人肠和培养的肠神经元中的定位和表达，并评估其通过神经营养因子胶质细胞源性神经营养因子（GDNF）的调节。在GDNF刺激的肠神经细胞培养物中分析SNAP-25的表达和分布，并通过扫描和透射电子显微镜评估突触囊泡。人结肠标本进行位点特异性SNAP-25基因表达分析和SNAP-25免疫组化，包括用泛神经元标记物PGP 9.5进行双标记。此外，SNAP-25的基因表达水平和分布模式进行了分析，在结肠憩室病（DD）患者的标本。GDNF处理的肠神经细胞培养物显示SNAP-25的丰富表达，并表现出对应于突触囊泡的颗粒染色。SNAP-25基因的表达在所有结肠层和分离的肌间神经节中检测到。SNAP-25与PGP 9.5共定位于粘膜下和肌间神经节和肌内神经纤维中。在DD患者中，与对照组相比，SNAP-25 mRNA表达和免疫反应谱均降低。GDNF诱导的培养肠神经元的生长和分化被SNAP-25表达的增加和反映突触发生增强的突触囊泡的形成所抑制。SNAP-25在人肠神经系统内的表达及其在DD中的下调表明在肠神经传递中的重要作用，并使SNAP-25成为肠运动障碍基础的肠神经病中突触可塑性受损的标志物。
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.