Can a human microglial atlas guide brain disorder research?


Researchers at Ikarn Medical College in Mount Sinai have analyzed the genetic activity of thousands of human microglia, the immune cells of the brain. Their results support the idea that microglia may play an important role in some brain disorders. Credits: Raj and de Witte labs, Mount Sinai, NY, NY

Certain subtle differences in DNA sequences are known to increase a person’s chances of developing Alzheimer’s disease or Parkinson’s disease. Some of these differences may function by altering the genetic activity of microglia, the immune cells of the brain. These are just a few of the discoveries from research led by scientists at Mount Sinai School of Medicine.

Researchers have analyzed thousands of microglia from different brain Areas of dead patients diagnosed with various neuropsychiatric and neurodegenerative disorders. Those results are Nature GeneticsSupports the idea that microglia may play an important role in some cases of brain disease, while providing a potentially valuable guide for future research.

This study was conducted by Katia de Paiva Lopes, Ph.D., Gijsje Snijders, MD, Ph.D. , And Jack Humphrey, Ph.D. Led by Towfique Raj, Ph.D. I worked at the Institute of Associate Professor. Associate Professor of Psychiatry at Neuroscience, and Lotje D. De Witte, MD, Ph.D., Icahn Mount Sinai.

Microglia shaped like octopi are scattered throughout the brain. For almost a century after they were first discovered, scientists believed that these cells acted as both an immune system to fight infections in the brain and a crew of purification. They also believed that microglia play a rigorous, rather than causative, reactive role in brain damage.

Recently, this view has begun to change. For example, experiments with rodents have shown that microglia can actively shape the way brains are wired. in the meantime, Genome research We have identified a potential association between microglia and the risk that certain DNA sequences are associated with the development of several brain disorders such as Alzheimer’s disease and multiple sclerosis.However, link these results to Specific gene Proven to be elusive.

In this study, scientists used advanced genomic technology to explore many of the possible roles that microglia can play in the brain. To do this, they created the largest and most thorough high-resolution microglial genome atlas of its kind. Microglia were extracted from a sample of human brain tissue and underwent a series of genetic activity experiments. A total of 255 samples representing four different brain regions were obtained from 100 donors who are part of the Netherlands Brain Bank and Neuropathology Brain Bank Research CoRE at Mount Sinai Hospital. The average donor was about 73 years old, ranging from 21 to 103 years old. Ninety-six samples were from control donors and the rest were from donors diagnosed with neuropathy or psychiatric disorders.

Overall, the results upheld previous discoveries and made new ones. For example, the genetic activity of microglia changes in different regions of the brain, including age, supporting the idea that the role of microglia can change throughout the brain and at different stages of life.In addition, aging appeared to alter the activity of primarily related genes. Immune system..

This result suggests that while microglia may be associated with some cases of Alzheimer’s disease and Parkinson’s disease, it is also associated with other disorders such as multiple sclerosis, schizophrenia, and bipolar disorder. Strengthened evidence that it may be.Finally, researchers have identified two new genes that may be related to the brain. hindrance..One gene called USP6NL, Was associated with Alzheimer’s disease, but the other one P2RY12, Was associated with Parkinson’s disease.According to the author, these results support the idea that Atlas provides a kind of comprehensive guide needed to fully understand the role. Microglia You can play in a healthy and sick state.

Methylation of microglia in the human brain “landscape”

For more information:
Lot Witte, Genetic Analysis of Human Microglial Transcriptome Throughout Brain Region, Pathology of Aging and Disease, Nature Genetics (2022). DOI: 10.1038 / s41588-021-00976-y..

Quote: Can Human Microglia Atlas Guide Research in Brain Disorders? (January 6, 2022) January 6, 2022 Obtained from

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