Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 42, Issue 12, Pages 2914-2925Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2016.07.017
Keywords
Low-intensity pulsed ultrasound; Nerve growth factor; Neurite outgrowth; Stretch-activated ion channels
Funding
- National Natural Science Foundation of China [81127901, 11674262]
- National Basic Research Program 973 of the Ministry of Science and Technology of China [2011 CB707903]
- Natural Science Basic Research Plan in Shaanxi Province of China [2015 JQ8313]
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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: fengyi@mail.xjtu.edu.cn or mxwan@mail.xjtu.edu.cn) (C) 2016 World Federation for Ultrasound in Medicine & Biology.
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