Neuroprotective Effect of Low-Intensity Pulsed Ultrasound Against MPP+-Induced Neurotoxicity in PC12 Cells: Involvement of K2P Channels and Stretch-Activated Ion Channels

Publication date: Available online 3 June 2017
Source:Ultrasound in Medicine & Biology
Author(s): Lu Zhao, Yi Feng, Aiwei Shi, Lei Zhang, Shifang Guo, Mingxi Wan
Parkinson's disease is the second most common neurodegenerative disease. It is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. 1-Methyl-4-phenylpyridinium (MPP⁺) is a dopaminergic neuronal toxin that is widely used in constructing Parkinson's disease models in vitro. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive therapeutic approach that has neuromodulation and neuroprotective effects in the central neural system; however, whether LIPUS can provide protection for dopaminergic neurons against MPP⁺-induced neurocytotoxicity remains unknown. In this study, we found that pre-treatment with LIPUS (1 MHz, 50 mW/cm², 20% duty cycle and 100-Hz pulse repetition frequency, 10 min) inhibited MPP⁺-induced neurotoxicity and mitochondrial dysfunction in PC12 cells. LIPUS decreased MPP⁺-induced oxidative stress by modulating antioxidant proteins, including thioredoxin-1 and heme oxygenase-1, and prevented neurocytotoxicity via the phosphoinositide 3-kinase (PI3K)-Akt and ERK1/2 pathways. Furthermore, these beneficial effects were attributed to the activation of K2P channels and stretch-activated ion channels by LIPUS. These data indicate that LIPUS protects neuronal cells from MPP⁺-induced cell death through the K2P channel- and stretch-activated ion channel-mediated downstream pathways. The data also suggest that LIPUS could be a promising therapeutic method in halting or retarding the degeneration of dopaminergic neurons in Parkinson's disease in a non-invasive manner.



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