Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer’s Disease Mouse Model
Fangxuan Chu, Ruxin Tan, Xin Wang, Xiaoqing Zhou, Ren Ma, Xiaoxu Ma, Ying Li, Ruixu Liu, Chunlan Zhang, Xu Liu, Tao Yin, Zhipeng Liu
Research 2023, 6 · 10.34133/research.0130
Abstract
The neuropathological features of Alzheimer's disease include amyloid plaques. Rapidly emerging evidence suggests that Piezo1, a mechanosensitive cation channel, plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure, but the importance of Piezo1-mediated mechanotransduction in brain functions is less appreciated. However, apart from mechanical stimulation, Piezo1 channels are strongly modulated by voltage. We assume that Piezo1 may play a role in converting mechanical and electrical signals, which could induce the phagocytosis and degradation of Aβ, and the combined effect of mechanical and electrical stimulation is superior to single mechanical stimulation. Hence, we design a transcranial magneto-acoustic stimulation (TMAS) system, based on transcranial ultrasound stimulation (TUS) within a magnetic field that combines a magneto-acoustic coupling effect electric field and the mechanical force of ultrasound, and applied it to test the above hypothesis in 5xFAD mice. Behavioral tests, in vivo electrophysiological recordings, Golgi-Cox staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, RNA sequencing, and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1. TMAS treatment enhanced autophagy to promote the phagocytosis and degradation of β-amyloid through the activation of microglial Piezo1 and alleviated neuroinflammation, synaptic plasticity impairment, and neural oscillation abnormalities in 5xFAD mice, showing a stronger effect than ultrasound. However, inhibition of Piezo1 with an antagonist, GsMTx-4, prevented these beneficial effects of TMAS. This research indicates that Piezo1 can transform TMAS-related mechanical and electrical stimuli into biochemical signals and identifies that the favorable effects of TMAS on synaptic plasticity in 5xFAD mice are mediated by Piezo1.
Abstract via europepmc.
Exposures
Exposure 1: TUS/TMAS acoustic exposure to hippocampus (5xFAD mice)
Target: hippocampus — “hippocampus”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | not reported |
| 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) | 300 | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 3 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 1.2 | ✓✓✓ |
TMAS combines TUS with a static magnetic field to generate a magneto-acoustic electric field; both TUS and TMAS groups received the same acoustic drive targeted at the hippocampus. The pulse train used a pulse repetition frequency (PRF) of 1 kHz with a pulse-train interval of 200 ms, giving an outer train-repetition frequency of 5 Hz. The stimulation-area schematic, pulse duration, duty cycle and total treatment duration/course are shown only in a supplementary figure (Fig. 1D) and Supplementary Materials, not in the accessible main text.
Flags from extraction
n_subjects— Main text (Materials and Methods refers entirely to Supplementary Materials) reports only per-experiment group sizes (n=8/group for behaviour, n=4/group for most histology/immunofluorescence, n=5/group for RNA-seq) across up to 6 groups (WT+Sham, AD+Sham, AD+TUS, AD+TMAS, AD+TUS+GsM, AD+TMAS+GsM); no single total number of animals used in the study is stated.exposures[0].fundamental_frequency_khz— Fundamental/carrier frequency of the TUS/TMAS system is not stated anywhere in the accessible main text; it may appear only in the supplementary Fig. 1D schematic or Supplementary Materials (not available).exposures[0].timing.waveform— Classified as other_patterned because the text describes a nested structure (1 kHz PRF pulses grouped into trains repeated every 200 ms/5 Hz) that does not clearly match 'pulsed' (simple PRF), 'theta_burst' (paper does not call it this), or 'continuous'; pulse duration and duty cycle needed to fully characterise the burst are not stated in the main text.sham_type— An 'AD + Sham' condition is used throughout the study but its mechanism (e.g., inactive transducer, sham TUS/TMAS device) is not described in the accessible main text.anaesthesia— Whether mice were anaesthetised during TUS/TMAS delivery is not stated in the accessible main text (Methods are in Supplementary Materials).