Gamma secretase activity modulates BMP-7-induced dendritic growth in primary rat sympathetic neurons

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 (?-secretase) complex, mutations in which are associ-ated with familial AD function, regulates dendritic growth in hippocampal neurons. In this study, we examined whether the ?-secretase pathway also influences dendritic growth in primary sympathetic neurons. Using immunoblotting and immunocytochemistry, molecules of the ?-secretase complex, PSEN1, PSEN2, PEN2, nicastrin and APH1a, were detected in sympathetic neurons dissociated from embryonic (E20/21) rat sympa-thetic ganglia. Addition of bone morphogenetic protein-7 (BMP-7), which induces dendrites in these neurons, did not alter expression or localization of ?-secretase complex proteins. BMP-7-induced dendritic growth was inhibited by siRNA knockdown of PSEN1 and by three ?-secretase inhibitors, ?-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 ?-secretase activity enhances BMP-7 induced dendritic growth in sympathetic neurons. These findings provide insight into the normal cellular role of the ?-secretase complex in sympathetic neurons.

Automated summary

This study explores the influence of genes involved in Alzheimer's disease (AD) on the peripheral nervous system and reveals that the ?-secretase pathway affects dendritic growth in sympathetic neurons. The findings provide insights into the cellular role of the ?-secretase complex in sympathetic neurons.