Wearable Ultrasound Improves Motor Function in an MPTP Mouse Model of Parkinson's Disease

Objective: Low-frequency low-intensity pulsed ultrasound (LIPUS) has emerged as a non-invasive neuromodulation tool. The aim of this study is to examine whether LIPUS stimulation of the motor cortex can improve parkinsonian motor deficit in a mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods: Acute Parkinson's disease (PD) mouse model is built by injection of MPTP (20 mg/kg) every 4 h in a total of four doses in one day. Mice are randomized into control, MPTP, sham-LIPUS+MPTP, and LIPUS+MPTP group. For LIPUS+MPTP group, 7 days of LIPUS (800 kHz, 10% duty cycle, 100-Hz pulse repetition frequency, 40 min/day) is delivered to the motor cortex. An open field test (OFT) is conducted on day 4 and a pole test on day 5, respectively. Striatal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) are measured on day 8. The safety of LIPUS is verified using Hematoxylin and esosin (HE) staining and Nissl staining. Results: LIPUS treatment improves rearing number in the OFT on day 4 (n = 8, p = 0.037) and locomotor activity in the pole test on day 5 (n = 8, p = 0.007) compared with the sham-LIPUS+MPTP group. Moreover, LIPUS increases T-SOD (n = 7, p = 0.006) and GSH-PX (n = 7, p = 0.030) compared with the sham-LIPUS+MPTP group. In addition, HE and Nissl staining shows no brain tissue injury induced by LIPUS. Conclusion: These findings demonstrate that LIPUS may have neuromodulation effects in PD mice. Significance: LIPUS may provide a novel neuromodulation tool for PD treatment.