Study advances search for a blood test to identify disease-associated changes in the brain

3 minutes, 54 seconds Read



Researchers in a Johns Hopkins Children’s Center-led study that used genetic material from human blood and lab-grown brain cells say they have made progress in developing a blood test to detect disease-related changes in the brain that are specific to postpartum depression and other conditions. Associated with mental illness. and neurological disorders.

The results of the study, published in January. 11 inches molecular psychiatry, The focus is on detecting the “footprint” of mRNA derived from brain cells in the circulation outside the brain. These extracellular vesicles carry pieces of brain-specific genetic material that enable researchers to detect disease-related changes in gene activity inside the brain.

Extracellular vesicles (EVs), fatty sacks of genetic material necessary for communication between cells, carry messenger RNA (mRNA) and are released by every tissue in the body, including the brain.

The new study was inspired, the researchers said, by the results of a study published in September 2022, in which Johns Hopkins Medicine scientists discovered that EV communication changes in pregnant women who develop postpartum depression after giving birth.

We only detected placenta-specific EVs during pregnancy, not after birth. This was a proof of concept, that we could identify EVs that were coming from a specific tissue or organ.”

Sarven Sabunsian, PhD, associate professor of pediatrics at Johns Hopkins University School of Medicine and senior author of the paper.

First, using the human placenta as a model, the investigators identified 26 placental mRNAs that are only present in the mother’s blood during pregnancy and not after birth, demonstrating that mRNAs from specific tissues are found in circulating EVs. Then, using lab-grown human brain tissue derived from stem cells (brain organoids), the researchers found that EV mRNAs from this brain tissue reflected changes occurring inside the tissue. Sabunsian and his team concluded that it is possible to gather biological information about normally inaccessible tissues such as the placenta and brain by examining EV mRNA circulating in the blood.

They were able to identify mRNA specifically expressed in the brain using data from the Human Protein Atlas -; A Swedish-based database of human proteins in cells, tissues and organs -; and the Genotype-Tissue Expression Project, which has comprehensively cataloged mRNA levels in human tissues.

Further analysis of those mRNA genetic pathways showed that brain-specific mRNAs in blood EVs were involved in specific brain functions and were significantly enriched for genes associated with brain disorders involving mood, schizophrenia, epilepsy, and substance abuse.

The research team says that this analysis suggests that these mRNAs could be ideal biomarkers for detecting such conditions.

“This is very exciting, because right now, there isn’t a blood marker for disorders that affect the brain,” said Lena Smirnova, Ph.D., an assistant professor in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health and co-author of the paper. Basically, these conditions are diagnosed by clinical interviews between patients and providers.”

The researchers discovered 13 brain-specific mRNAs in the blood that were found to be associated with postpartum depression. To determine whether blood EV mRNAs reflect transcription in the brain, the researchers compared mRNAs isolated from cells and EVs in an organoid model of the brain. They found that although cellular and extracellular mRNA levels are not identical, they are correlated and it is possible to extrapolate cellular expression changes in the brain through EV mRNA levels.

The goal is to develop a simple blood test to detect changes in high or low levels of EV mRNAs that are associated with brain changes associated with psychiatric disorders without directly entering the brain, Sabunsian said.

Finally, Sabunsian added, the availability of such blood tests could enable detection of early signs of mental health emergencies, such as suicidal behavior. The ability to identify patients at risk of developing psychiatric disorders will enable care teams to intervene and possibly prevent negative outcomes.

In future research, they plan to use lab-grown brain samples to identify similar biomarkers to develop tests for autism spectrum disorders.

The researchers caution that the differences identified with depression may only be associated with postpartum depression because the study was conducted using only a sample of female participants.

Along with Sabunsian and Smirnova, the authors are Johns Hopkins’ Sergio Modafferi and Charlotte Schlett; Lauren Osborne from Weill Cornell Medicine; and Jennifer Payne from the University of Virginia.

The research was funded by grants from the National Institutes of Health under grant number NIH-NIMH R01 MH112704, NIH-NIMH 1K23 MH110607 R01ES034554.

Source:

Journal Reference:

Smirnova, L., Modafferi, S., Schlett, C., Osborne, LM, Payne, JL, & Sabunciyan, S. (2024). Blood extracellular vesicles carrying brain-specific mRNA are potential biomarkers for detecting gene expression changes in the female brain. Molecular Psychiatry. doi.org/10.1038/s41380-023-02384-6.



Similar Posts

Leave a Reply

Your email address will not be published. Required fields are marked *