A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of A&#946; and Tau Levels in Rhesus Monkey Cerebrospinal Fluid

Ling-Yi Liao; Ying-Qian Zhang; Benson Wui-Man Lau; Qiong Wu; Zi-Yan Fan; Qiang Gao; Zhi-Hui Zhong

doi:10.3791/63005

A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of Aβ and Tau Levels in Rh...

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Neuroscience

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JoVE Journal Neuroscience

A Pilot Study on the Repetitive Transcranial Magnetic Stimulation of Aβ and Tau Levels in Rhesus Monkey Cerebrospinal Fluid

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06:22 min

September 3, 2021

DOI: 10.3791/63005-v

Ling-Yi Liao^1,2,3, Ying-Qian Zhang⁴, Benson Wui-Man Lau⁵, Qiong Wu⁶, Zi-Yan Fan^1,3, Qiang Gao^1,3, Zhi-Hui Zhong^6,7

¹Department of Rehabilitation Medicine, West China Hospital,Sichuan University, ²Department of Rehabilitation Medicine, Daping Hospital,Army Medical University, ³Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital,Sichuan University, ⁴Department of physiology,Southwest Medical University, ⁵Department of Rehabilitation Sciences,The Hong Kong Polytechnic University, ⁶Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital,Sichuan University, ⁷Sichuan Kangcheng Biotech Co., Inc.

Overview

This study investigates the effects of repetitive transcranial magnetic stimulation (rTMS) at different frequencies (1 Hz, 20 Hz, and 40 Hz) on the metabolism of amyloid-beta (Aβ) and tau proteins in the cerebrospinal fluid (CSF) of rhesus monkeys. The research utilizes a novel CSF sampling technique under fully awake conditions to assess changes in biomarker levels post-rTMS intervention.

Key Study Components

Area of Science

Neuroscience
Neurochemistry
Transcranial magnetic stimulation

Background

Repetitive transcranial magnetic stimulation (rTMS) is explored as a potential method to influence neurodegenerative biomarkers.
Aβ and tau are critical in understanding Alzheimer's disease and related conditions.
The study employs a pilot investigation, emphasizing a novel approach to CSF sampling.
Research was conducted with a male rhesus monkey model, relevant for translational research in neurodegenerative studies.

Purpose of Study

To assess the impact of varying rTMS frequencies on the levels of Aβ and tau in CSF.
To validate the repeated CSF sampling method under awake conditions with minimal risk.
To investigate potential biomarkers associated with cognitive function and neurodegeneration.

Methods Used

The protocol employs serial cisterna magna CSF sampling.
The biological model is a male rhesus monkey subjected to rTMS intervention.
No multiomics workflows are highlighted in the methodology.
Key steps include anaesthesia confirmation, catheterization, adaptive training, and rTMS application.
CSF collection occurs at multiple time points following rTMS stimulation.

Main Results

Post-stimulation, Aβ levels showed differential responses based on frequency, with significant increases noted after 1 Hz and 20 Hz interventions.
tTau levels increased significantly after 20 Hz and 40 Hz stimulation.
pTau levels exhibited a notable increase immediately post 40 Hz stimulation.
No significant changes in tau levels were observed after 1 Hz stimulation.

Conclusions

This study demonstrates the feasibility of using rTMS to modulate key neurodegenerative biomarkers in awake non-human primates.
Findings enhance understanding of how rTMS can influence the metabolism of Aβ and tau, contributing valuable insights into therapeutic interventions for neurodegenerative diseases.
The developed CSF sampling method may serve as an important tool for future studies on biomarker dynamics in primate models.

Frequently Asked Questions

What are the advantages of the rTMS method used in this study?

The rTMS method allows non-invasive modulation of neural activity while monitoring changes in cerebrospinal fluid biomarkers under awake conditions, minimizing risk.

How is the CSF sampling conducted in this research?

CSF is sampled using a serial cisterna magna approach with an implanted catheter, allowing for multiple collections without anesthesia.

What biological data are obtained through this method?

The primary outcomes include changes in amyloid-beta and tau protein levels in the CSF, which are crucial for understanding neurodegenerative processes.

How can this method be adapted for other studies?

Researchers can modify the stimulation frequencies and biomarker targets to suit various neurobiological investigations in primate models.

What limitations should be considered with this approach?

While the method is safe, the specific impacts of rTMS on cognitive function in long-term studies remain to be elucidated.

What implications do these findings have for future research?

The findings could inform therapeutic strategies targeting neurodegenerative biomarkers and advance understanding of rTMS efficacy in clinical settings.

Here, we describe the procedure for a pilot study to explore the effect of repetitive transcranial magnetic stimulation with different frequencies (1 Hz/20 Hz/40 Hz) on Aβ and tau metabolism in rhesus monkey cerebrospinal fluid.

This protocol uses serial cisterna magna CSF sampling method to explore the effects of rTMS on alpha-beta and tau levels in rhesus monkey. This technique uses a novel CSF sampling method allowing for repeated CSF sampling under fully awake conditions with low risks of adverse events. Demonstrating the procedure will be Ying-Qian Zhang, a research assistant from the Department of Physiology at Southwest Medical University, and Hui-Xin Tan, a graduate student from Sichuan University.

After administering analgesia and confirming successful anesthetization, place the five-year-old male rhesus monkey on the operating table in the lateral decubitus position and disinfect the area around the lower back. Hunch its back and bring its knees toward the chest. Insert a spinal needle between the lumbar vertebrae L4 to L5 and push it in until there is a pop indicating entry into the lumbar cistern where the ligamentum flavum is housed.

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