Transcranial Ultrasound Stimulation of Hypothalamus in Aging Mice

The hypothalamus plays an important role in the control of aging. Transcranial ultrasound stimulation (TUS) has been reported as a noninvasive method of neuromodulation. However, the effect of TUS of the hypothalamus on aging remains unclear. Therefore, the aim of this study is to verify whether TUS of the hypothalamus could affect the behaviors of aging mice and the expression level of apoptosis factors and inflammatory cytokines. TUS was delivered to the hypothalamus of mice (n = 44) for 14 days (15 min/day) at a fundamental frequency of 1 MHz, pulse repetition frequency of 1 kHz (US1) or 10Hz (US2), duty cycle of 10%, and acoustic pressure of 0.13 MPa. The effect of TUS on aging was evaluated by the behavioral tests or Western blotting in different stages. The behavioral results showed that mice in the US2 group improved their movement and learning. In addition, there was a significant improvement in the grip strength after TUS in the second behavioral tests (Sham: 0.0351 ± 0.0020 N/g; US1: 0.0340 ± 0.0023 N/g; US2: 0.0425 ± 0.0029 N/g, p = 0.034). Furthermore, the level of inflammation (TNF-α: Sham: 0.69 ± 0.084; US1: 0.39 ± 0.054; US2: 0.49 ± 0.1, p = 0.021) and apoptosis (Bax: Sham: 0.47 ± 0.049; US1: 0.42 ± 0.054; US2: 0.18 ± 0.055, p = 0.001) was significantly reduced after TUS in this stage. We did not see a long-lasting effect of TUS in the third behavioral tests. In addition, we found that TUS is safe according to hematoxylin and eosin (HE) staining. In conclusion, TUS could effectively modulate the hypothalamus, which may provide a new method for controlling aging.