Pitt Shield

Transcranial Magneto-Acoustic Stimulation Improves Neuroplasticity in Hippocampus of Parkinson's Disease Model Mice.

Authors: Wang Y, Feng L, Liu S, Zhou X, Yin T, Liu Z, Yang Z

In this study, we have, for the first time, demonstrated the beneficial effects of transcranial magneto-acoustic stimulation (TMAS), a technique based on focused ultrasound stimulation within static magnetic field, on the learning and memory abilities and neuroplasticity of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Our results showed that chronic TMAS treatment (2 weeks) improved the outcome of Morris water maze, long-term potentiation (LTP), and dendritic spine densities in the dentate gyrus (DG) region of the hippocampus of PD model mice. To further investigate into the underlying mechanisms of these beneficial effects by TMAS, we quantified the proteins in the hippocampus that regulated neuroplasticity. Results showed that the level of postsynaptic density protein 95 was elevated in the brain of TMAS-treated PD model mice while the level of synaptophysin (SYP) did not show any change. We further quantified proteins that mediated neuroplasticity mechanisms, such as brain-derived neurotrophic factor (BDNF) and other important proteins that mediated neuroplasticity. Results showed that TMAS treatment elevated the levels of BDNF, cAMP response element-binding protein (CREB), and protein kinase B (p-Akt) in the PD model mouse hippocampus, but not in the non-PD mouse hippocampus. These results suggest that the beneficial effects on the neuroplasticity of PD model mice treated with TMAS could possibly be conducted through postsynaptic regulations and mediated by BDNF.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To evaluate whether transcranial magneto-acoustic stimulation (TMAS) improves learning, memory, and neuroplasticity in an MPTP mouse model of Parkinson’s disease and to investigate the underlying molecular mechanisms.
Animal model / Human subject Male C57BL mice, 8 weeks old
Disease model Parkinson's disease
MRI or image guidance method Stereotaxic
Targeted brain region(s) Substantia Nigra
Target coordinates AP -3.4 mm, ML 1.5 mm, DV 4.5 mm

Outcomes and Safety

Summary of Outcomes Chronic TMAS applied to the substantia nigra for 2 weeks improved learning, memory, hippocampal LTP, and dendritic spine density in a Parkinson's disease mouse model. These cognitive benefits were associated with increased levels of neuroplasticity-related proteins like PSD-95 and BDNF.
Duration of biological effect 2 weeks
Safety-related matter No safety concerns or adverse effects were reported.

Brain Region

Ultrasound Parameters

Ultrasound instrument TMAS-ESA-BME01 with 0.17 T static magnetic field
FUS Frequency 1 MHz
FUS Intensity 63 mW/cm2 Ispta
FUS Pressure 2.35 Mpa
FUS Mode pulsed
Pulse duration 8 µs
Duration of a single FUS session 60 s
Focal Characteristics Focal diameter: 2 mm
Treatment frequency Multiple sessions

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