Autonomic dysfunction has been observed in Alzheimer's disease (AD); however, the effects of genes involved in AD on the peripheral nervous system are not well understood. Previous studies have shown that presenilin-1 (PSEN1), the catalytic subunit of the gamma secretase (γ-secretase) complex, mutations in which are associated with familial AD function, regulates dendritic growth in hippocampal neurons. In this study, we examined whether the γ-secretase pathway also influences dendritic growth in primary sympathetic neurons. Using immunoblotting and immunocytochemistry, molecules of the γ-secretase complex, PSEN1, PSEN2, PEN2, nicastrin and APH1a, were detected in sympathetic neurons dissociated from embryonic (E20/21) rat sympathetic ganglia. Addition of bone morphogenetic protein-7 (BMP-7), which induces dendrites in these neurons, did not alter expression or localization of γ-secretase complex proteins. BMP-7-induced dendritic growth was inhibited by siRNA knockdown of PSEN1 and by three γ-secretase inhibitors, γ-secretase inhibitor IX (DAPT), LY-411575 and BMS-299897. These effects were specific to dendrites and concentration-dependent and did not alter early downstream pathways of BMP signaling. In summary, our results indicate that γ-secretase activity enhances BMP-7 induced dendritic growth in sympathetic neurons. These findings provide insight into the normal cellular role of the γ-secretase complex in sympathetic neurons.

在阿尔茨海默病 (AD) 中观察到自主神经功能障碍；然而，AD 相关基因对周围神经系统的影响尚不清楚。先前的研究表明，早老素-1（PSEN1）是γ分泌酶（γ-分泌酶）复合物的催化亚基，其突变与家族性AD功能相关，可调节海马神经元的树突状生长。在这项研究中，我们检查了γ-分泌酶途径是否也影响初级交感神经元的树突生长。使用免疫印迹和免疫细胞化学，γ-分泌酶复合物、PSEN1、 PSEN2 、PEN2、尼卡斯特林的分子和 APH1a，在从胚胎 (E20/21) 大鼠交感神经节分离的交感神经元中检测到。添加骨形态发生蛋白 7 (BMP-7) 会在这些神经元中诱导树突，但不会改变 γ-分泌酶复合物蛋白。siRNA 抑制 BMP-7 诱导的树突生长PSEN1 的敲低以及三种 γ-分泌酶抑制剂：γ-分泌酶抑制剂 IX (DAPT)、LY-411575 和 BMS-299897。这些效应是树突特有的且具有浓度依赖性，并且不会改变 BMP 信号传导的早期下游途径。总之，我们的结果表明，γ-分泌酶活性增强了 BMP-7 诱导的交感神经元树突生长。这些发现提供了对γ-分泌酶复合物在交感神经元中的正常细胞作用的深入了解。