Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions
Chunlan Zhang, Ruxin Tan, Xiaoqing Zhou, Ruru Wang, Xin Wang, Ren Ma, Fangxuan Chu, Ying Li, Tao Yin, Zhipeng Liu
International Journal of Molecular Sciences 2024 · 10.3390/ijms25094651
Abstract
Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aβ) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aβ. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aβ plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.
Abstract via europepmc.
Exposures
Exposure 1: TUS and TMAS (with static magnet), bilateral hippocampus of 5xFAD mice
Target: hippocampus — “bilateral hippocampus”
Device: other named manufacturer · IOA-AC, Beijing, China · FP-0.5M ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.6 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 60%, which disagrees with the stated value | ✓✓✓⚑ |
| Sonication duration (s) | 0.4 | ✓✓✓⚑ |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 0.106 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.053 | ✓✓✓ |
0.6 ms tone bursts at 1 kHz PRF for a 400 ms sonication duration (TUS parameters); Results describe a 300 ms ultrasonic pulse excitation signal followed by a 4000 ms ultrasound interval. 5 min daily treatment for 2 weeks. TMAS adds a 0.15 T static magnet.
Flags from extraction
exposures[0].timing.sonication_duration_s— Methods give 400 ms SD, Results describe a 300 ms excitation signal with 4000 ms interval; recorded 400 ms as stated in methodsexposures[0].timing.duty_cycle_pct— Not stated; 0.6 ms at 1 kHz would not match the 300 ms/4000 ms description, so no duty cycle recordedexposures[0].unspecified_domain.isppa_w_cm2— 106 mW/cm2 Isppa; needle hydrophone is mentioned but domain not statedn_subjects— Two cohorts of 7 mice per group (TUS, TMAS, sham); sizes of the four ultrasound-exposed groups listed; sham and wild-type groups not countedblinding— Treatment conditions were blinded until pathology analyses completed; blinding level not describedexposures[0].device.family— Transducer FP-0.5M credited to IOA-AC, Beijing (taken as Institute of Acoustics); family set to other_manufacturermodel_system— BV2 cell experiments also used TUS, TMAS and sham but their ultrasound parameters are not given separately