15 Apr Why Do the Identical-Looking Brain Hemispheres Act Differently?

MedicalResearch.com Interview with:

Dr. Labrie

Dr. Viviane Labrie, PhD
Dr. Labrie is an associate professor in Van Andel Institute’s Center for Neurodegenerative Science, where she studies Parkinson’s, Alzheimer’s and other neurological diseases.

MedicalResearch.com: What is the background for this study?

Response: One of the most puzzling and persistent mysteries in neuroscience has been why some people are “right-brained” while others are “left-brained.” The two sides of the brain have different jobs. The left side is analytic and problem-solving, while the right side manages creativity and artistic talents. But despite their differences, the two sides are composed of the same cell types — essentially, brain neurons and their support cells. In this study, we sought to understand how it is possible for these cells to behave completely differently depending on what hemisphere they’re located in. 

We also wanted to examine the reasons behind asymmetry in Parkinson’s disease; that is, why Parkinson’s symptoms typically start on one side of the body before the other. This asymmetry in neurodegeneration and symptoms in patients is one of the biggest unsolved puzzles in the Parkinson’s disease field — why do brain cells in one hemisphere begin dying before brain cells in the other hemisphere?

MedicalResearch.com: What are the main findings? What are the implications for Parkinson’s disease?

Response: We found that hemispheric differences are related to molecular modifications on DNA that help determine the “day job” of a brain cell. Two cells that look totally identical can behave differently because of the molecular, or epigenetic, marks on the cell’s DNA.

Each cell in the brain has the same genes, but it is epigenetics that dictate whether those genes are switched “on” or “off.” Our team found numerous epigenetic differences between the hemispheres of healthy brains that are linked to variations in gene activity. This is important to our fundamental understanding how our brain is built and works.

It may also contribute to understanding the asymmetric nature of Parkinson’s disease. In the same study, we found that asymmetry in Parkinson’s disease is associated with variations in these epigenetic marks in brain neurons that affect brain development, chemical signaling and immune activation. In other words, epigenetic abnormalities on one side of the brain could make that hemisphere more susceptible to the processes that cause the death of brain cells in Parkinson’s.

MedicalResearch.com: What should readers take away from your report? 

Response: Both hemispheres of the brain may, at first glance, look identical in structure — comprising brain neurons and their helper cells — but molecular-level patterns in the cell’s DNA can cause vastly different behaviors in each hemisphere and enable asymmetry in the brain.

As it relates to Parkinson’s disease, the brain appears to be wired at the molecular level such that one hemisphere is more vulnerable to neurogenerative processes than the other. The differences in cell death across hemispheres leads to the appearance of the disease’s hallmark symptoms, such as tremors, on one side of the body before the other 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We are already looking at how the molecular differences that may cause brain asymmetry come into play in other diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), multiple sclerosis and schizophrenia.

Understanding how hemispheric differences in the brain affect disease progression sheds light on underlying factors of the disease, which has huge potential for translating into new therapeutic strategies.

Disclosures: Other authors include Peipei Li, Ph.D., Elizabeth Ensink, Sean Lang, Lee Marshall, Ph.D., and Meghan Schilthuis of Van Andel Institute; and Jared Lamp, Ph.D., and Irving Vega, Ph.D., of Michigan State University College of Human Medicine. The Flow Cytometry Core, Bioinformatics and Biostatistics Core and Pathology and Biorepository Core at Van Andel Institute and Integrated Mass Spectrometry Unit at Michigan State University also contributed to this work. Brain tissue was provided by the Parkinson’s UK Brain Bank, the NIH NeuroBioBank and the Michigan Brain Bank.

This work was supported by Van Andel Institute.

Labrie is supported by the U.S. Army Medical Research Materiel Command through the Parkinson’s Research Program Investigator-Initiated Research Award under award no. W81XWH1810512. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the U.S. Army. Labrie also is supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R21NS112614 and by Michigan State University through the Gibby & Friends vs. Parky Parkinson’s Disease Research Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other granting organizations.

Citation:

Peipei Li, Elizabeth Ensink, Sean Lang, Lee Marshall, Meghan Schilthuis, Jared Lamp, Irving Vega, Viviane Labrie. Hemispheric asymmetry in the human brain and in Parkinson’s disease is linked to divergent epigenetic patterns in neurons. Genome Biology, 2020; 21 (1) DOI: 10.1186/s13059-020-01960-1

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Last Updated on April 15, 2020 by Marie Benz MD FAAD