Transcranial Ultrasound Stimulation of Hypothalamus in Aging Mice
Na Pang, Xiaowei Huang, Hui Zhou, Xiangxiang Xia, Xiufang Liu, Yibo Wang, Wen Meng, Tianyuan Bian, Long Meng, Lisheng Xu, Lili Niu
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2021 · 10.1109/tuffc.2020.2968479
Abstract
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 10 Hz (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.
Abstract via europepmc.
Exposures
Exposure 1: US1 (PRF 1 kHz) and US2 (PRF 10 Hz), hypothalamus
Target: ventromedial hypothalamus — “ventromedial hypothalamic nucleus (VHM)”
Device: other named manufacturer · NdtXducer (Northborough, MA, USA) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 0.1, 10swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000, 10swept | ✓✓✓ |
| Duty cycle (%) | 10 | ✓✓✓⚑ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 130 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 5.4 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.54 | ✓✓✓ |
US1: 100-us pulse of 100 cycles at 1 MHz, PRF 1 kHz; US2: 10-ms pulse of 10 000 cycles, PRF 10 Hz; sonication duration 1 s, interstimulus interval 5 s. Delivered 15 min/day for 14 days in each of two FUS sessions.
Consistency checks: intensity pressure inconsistent unspecified domain.
Flags from extraction
exposures[0].unspecified_domain.pressure_kpa— 0.13 MPa given without stating domain; hydrophone calibration mentioned, with and without skull distributions in Fig. 1(d) only; kind of pressure (peak negative vs peak) not statedexposures[0].target.terms— Paper writes ventromedial hypothalamic nucleus abbreviated VHM; mapped to ventromedial_hypothalamusn_subjects— 44 mice total; fewer analysed per assay (group sizes in figure legends vary, e.g. n=3 to 15)exposures[0].timing.duty_cycle_pct— Duty cycle 10% stated for both PRFs; 100 us x 1 kHz and 10 ms x 10 Hz are consistent but not computed hereexposures[0].device.family— NdtXducer named as transducer source without a parent manufacturer; assigned other_manufacturern_sessions_per_subject— Two FUS sessions of 14 daily 15-min treatments each; session count not summed to a total number of days