LOW-INTENSITY PULSED ULTRASOUND ENHANCES NERVE GROWTH FACTOR-INDUCED NEURITE OUTGROWTH THROUGH MECHANOTRANSDUCTION-MEDIATED ERK1/2-CREB-Trx-1 SIGNALING

作者：Zhao, Lu; Feng, Yi^*; Hu, Hong; Shi, Aiwei; Zhang, Lei; Wan, Mingxi^*

来源：Ultrasound in Medicine and Biology, 2016, 42(12): 2914-2925.

DOI：10.1016/j.ultrasmedbio.2016.07.017

• Low-intensity pulsed ultrasound
• Nerve growth factor
• Neurite outgrowth
• Stretch-activated ion channels

Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm(2), 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared. Our findings indicated that the combined treatment with LIPUS (50 mW/cm(2)) and NGF (50 ng/mL) promotes neurite outgrowth that is comparable to that achieved by NGF (100 ng/mL) treatment alone. LIPUS significantly increased NGF-induced neurite length, but not neurite branching. These effects were attributed to the enhancing effects of LIPUS on NGF-induced phosphorylation of ERK1/2 and CREB and the expression of thioredoxin (Trx-1). Furthermore, blockage of stretch-activated ion channels with Gd3+ suppressed the stimulating effects of LIPUS on NGF-induced neurite outgrowth and the downstream signaling activation. Taken together, our findings suggest that LIPUS enhances NGF-induced neurite outgrowth through mechanotransduction-mediated signaling of the ERK1/2-CREB-Trx-1 pathway. The combination of LIPUS and NGF could potentially be used for the treatment of nerve injury and neurodegenerative diseases. (E-mail: [e-mail] or [e-mail].

• 出版日期2016-12
• 单位西安交通大学