Ultrasound deep brain stimulation decelerates telomere shortening in Alzheimer's disease and aging mice
Yaya Zhang, Na Pang, Xiaowei Huang, Wen Meng, Long Meng, Bingchang Zhang, Zhengye Jiang, Jing Zhang, Zhou Yi, Zhiyu Luo, Zhanxiang Wang, Lili Niu
Fundamental Research 2023, 3, 469-478 · 10.1016/j.fmre.2022.02.010
Abstract
Telomere length is a reliable biomarker for health and longevity prediction in both humans and animals. The common neuromodulation techniques, including deep brain stimulation (DBS) and optogenetics, have excellent spatial resolution and depth penetration but require implementation of electrodes or optical fibers. Therefore, it is important to develop methods for noninvasive modulation of telomere length. Herein, we reported on a new method for decelerating telomere shortening using noninvasive ultrasound deep brain stimulation (UDBS). Firstly, we found that UDBS could activate the telomerase-associated proteins in normal mice. Then, in the Alzheimer's disease mice, UDBS was observed to decelerate telomere shortening of the cortex and myocardial tissue and to effectively improve spatial learning and memory abilities. Similarly, UDBS was found to significantly slow down telomere shortening of the cortex and peripheral blood, and improve motor and cognitive functions in aging mice. Finally, transcriptome analysis revealed that UDBS upregulated the neuroactive ligand-receptor interaction pathway. Overall, the present findings established the critical role of UDBS in delaying telomere shortening and indicated that ultrasound modulation of telomere length may constitute an effective therapeutic strategy for aging and aging-related diseases.
Abstract via europepmc.
Exposures
Exposure 1: UDBS of hippocampus and cortex (normal, AD-model, and aging mice)
Target: hippocampus, cerebral cortex — “hippocampus and cortex”
Device: other named manufacturer · NdtXducer, Northborough, USA ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.1 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 5 | ✓✓✓ |
| 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) | 340 | ✓✓✓ |
UDBS delivered with 1 s sonication trains and a 1 s inter-stimulus interval, for 30 min/day. Experiment 1 (normal mice): treated for 14 days then sacrificed for telomerase western blotting. Experiment 2 (APP/PS1 Alzheimer's model mice): UDBS administered for 66 days, then behavioural testing and sacrifice for telomere evaluation on Day 100. Experiment 3 (aging mice): treated for 49 days, with behavioural, telomere, immunofluorescence and transcriptomic evaluation.
Flags from extraction
n_subjects— Value is the sum of UDBS-exposed animals across three sub-experiments (3 normal + 10 APP/PS1 + 10 aging mice); sham-treated animals from each group (3+10+10) are excluded as they received no acoustic output.n_sessions_per_subject— The three sub-experiments used different treatment durations (14, 66, and 49 days respectively), so a single session count cannot be given; durations are described in protocol_description.exposures[0].timing.pulse_duration_ms— Not stated; duty cycle (5%) and PRF (500 Hz) are both given but pulse duration is not explicitly stated by the paper, so it is not computed.