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Spinning-Disk Confocal Microscopy Advances Brain Myelin Research for Alzheimer's Disease

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Myelin research for Alzheimer's disease

Dementia is a broad term that describes the loss of cognitive functions such as memory, language, reasoning, and other thinking abilities. According to the World Health Organization (WHO), 139 million people worldwide are expected to have dementia by 2050. Alzheimer's disease (AD) is the most common cause of dementia and may account for 60–70% of all dementia cases.

Alzheimer's disease is a progressive disorder, which means the dementia symptoms develop gradually over many years and eventually become more severe. The cause of AD is unknown, the pathogenesis of AD is not well understood, and there is no effective treatment.

One target to expand our understanding of AD is myelin, a sheath-like material in the brain that insulates nerve fibers (axons) and accelerates nerve impulse conduction. Recent studies (Steadman et al., 2020; Pan et al., 2020; Wang et al., 2020) show that myelin formation in adult mice is closely related to spatial memory and that reduced myelin formation is one of the causes of age-related decline in memory function.

In a recent study, Professor Feng Mei's team from the School of Basic Medical Sciences of the Army Medical University (Third Military Medical University) revealed the dynamic changes of myelin that occurs with AD using high-resolution imaging of brain sections (Chen et al., 2021).

In this interview, Kai Jin of the Marketing and Sales Division at Evident China and Hongxia Zheng of Chengdu Zhixin Technology Co. Ltd. spoke to Professor Feng Mei and Researcher Dr. Jingfei Chen about their research and their experience imaging brain sections.

Q: What changes and roles does myelin have in a brain with Alzheimer's disease?

A: Using transgenic mice with cell-specific fluorescent reporters, we observed myelin formation and revealed unique myelin dynamics in the brains of APP/PS1 mice (an AD mouse model). Conditional knockout mice, behavioral studies, and electrophysiological experiments demonstrate that accelerated myelin turnover can reduce memory loss and hippocampal physiological dysfunction in AD mice.

The main result of the study is that myelin regeneration could be enhanced in the AD mouse brain even after extensive demyelination, leading to improved cognitive function. This demonstrates that promoting myelin formation through genetic modification or pharmacological intervention may effectively ameliorate AD-induced phenomena, and represents a promising therapeutic approach to alleviate AD-related symptoms.

Q: What technical difficulties did you encounter while imaging the brain sections?

A: Our group needed to acquire images of multiple brain regions, such as the cortex, hippocampus, and corpus callosum. This requires rapid multidimensional and multichannel imaging of brain slices. An additional challenge was that the signal in transgenic brain slices with cell-specific fluorescent reporters can quickly fade due to photobleaching.

As a result, we needed imaging equipment to meet the following demands:

  1. The signal of the cell-specific fluorescent reporter gene is weak and fades easily, so high-sensitivity and high-speed imaging was required.
  2. With various brain regions involved, we needed to observe changes in the myelin sheath at multiple locations. We also required a stitched image of the entire brain slice to avoid subjectivity when selecting the field of view.
  3. Myelin and microglia have three-dimensional structures, so we needed to take three-dimensional images with high resolution in the Z-axis.

In the early stages of the project, experiments were conducted using conventional single-point laser scanning confocal microscopes. Although single-point scanning microscopes can produce high-quality images in a single field of view, many images must be stitched into one to acquire an image of a large area, which is time consuming. The fluorescent markers also faded due to light irradiation on the specimen.

After much study, we found that the IXplore™ Spin system, a spinning-disk confocal microscope with high-speed scanning, low phototoxicity, and automated features such as image stitching and multi-point imaging, saves a great deal of time during the experiment.

Q: What role did the IXplore Spin system play in obtaining the experimental results?

A: The IXplore Spin system acquired images more than 30 times faster than our conventional single-point laser scanning confocal microscope. If, hypothetically, a conventional single-point laser scanning confocal microscope takes 3–4 hours to image, the IXplore Spin system can do so in only about 10 minutes.

The study required imaging of whole brain slices from approximately 60 mice. Using the IXplore Spin system greatly reduced the time spent on image acquisition and enabled us to rapidly execute the project. At the same time, the IXplore spinning-disk confocal microscope allows for repeatable imaging with high sensitivity, low phototoxicity, and minimal damage to the fluorescent specimens.

Learn More about the IXplore Spin Microscope System

The IXplore microscope series refers to inverted microscopes tailored to different life science research applications. The IXplore Spin microscope system uses an advanced spinning disk unit to provide high-speed 3D confocal imaging, a large field of view, and prolonged cell viability in time-lapse experiments.

Benefits include:

  • Enhanced Z-resolution
  • Automated image stitching
  • Precise 3D imaging deep within thick samples
  • Reduced phototoxicity and bleaching
  • Can be upgraded to the SpinSR super-resolution module

The Interviewees: Professor Feng Mei and Researcher Jingfei Chen

Professor Feng Mei, Associate Professor at the Third Military Medical University

Professor Feng Mei

Feng Mei received his PhD from the University of California, San Francisco, and is currently an Associate Professor at the Army Medical University (Third Military Medical University) in Chongqing, China. His group has long studied the role of dynamic changes of myelin in brain development and disease and published an article in the June 8, 2021, online edition of Neuron entitled, “Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer’s disease.

Jingfei Chen conducts research in the department of Histology and Embryology at the Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of the Chongqing Education Commission, Army Medical University (Third Military Medical University) in Chongqing, China.

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Life Science Research Marketing Representative

Since joining the company, Hikaru has been responsible for supporting confocal and super-resolution microscopy products, and she has been a member of the Life Science Marketing department since 2022. Hikaru holds a Bachelor of Science degree from Tokyo University of Science, Japan.

Jan 31 2023
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