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A new study focuses on the methylation profile of microglia from the human brain

A new study focuses on the methylation profile of microglia from the human brain

 


In the central nervous system, microglial cells play important roles in development, aging, brain homeostasis, and pathology. Recent studies have shown that microglial gene expression profiles and phenotypes vary across brain regions and across different ages and medical conditions. However, the molecular mechanisms that contribute to these transcriptmic changes in the human brain are not well understood. Currently, a new study focuses on the methylation profile of microglia from the human brain.

The study will be displayed in biological Psychiatry, Published by Elsevier.

Microglia, the immune cells of the brain itself, were once “activated” or “inactivated” and were considered a homogeneous population with pro-inflammatory or neuroprotective effects. However, cells are now recognized to have a vast number of phenotypes, depending on environmental conditions with innumerable functional consequences. Microglia are increasingly valued as important players in neurological and psychiatric disorders.

Senior authors of the new work, Fatemeh Haghighi, PhD, said:

DNA methylation is the main form of epigenetic regulation and determines which genes are “on” or “off” over time in a variety of situations.

The researchers were isolated from postmortem human brain tissue from 22 donors of various ages, including one patient with schizophrenia, 13 patients with mood disorders, and eight controls without psychiatric disorders. Microglial cells were collected from four brain regions and studied. They analyzed microglia using a genome-scale methylated microarray.

Not surprisingly, microglia showed a different DNA methylation profile than other cells in the central nervous system. But less than expected, Haghighi said, “We found that differences between individuals, rather than differences in brain regions, have a far greater impact on changes in DNA methylation.” In addition, exploratory analysis showed differences in the methylation profile of microglia from the brains of subjects with mental illness compared to controls.

These promising data show the pathology of microglia, an important immune cell in the brain in the biology of depression... “

John Crystal, MD, Editor Biological psychiatry

Source:

Journal reference:

de Witte, LD, et al.. (2021) Contribution of interpersonal factors to age, brain region, pathology of mood disorders, and methyrome of human microglia. Biological psychiatry.. doi.org/10.1016/j.biopsych.2021.10.020..

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