In the central nervous system, microglial cells play an essential role in development, aging, brain homeostasis and pathology. Recent studies have shown variations in the gene expression profile and phenotype of microglia across regions of the brain and between different ages and disease states. But the molecular mechanisms that contribute to these transcriptomic changes in the human brain are not well understood. Now, a new study targets the methylation profile of human brain microglia.
The study appears in Biological Psychiatry, published by Elsevier.
Microglia, the brain’s own immune cells, were once thought to be a homogeneous population that was either “activated” or “inactivated”, with pro-inflammatory or neuroprotective effects. But cells are now recognized to have a wide range of phenotypes depending on environmental conditions with a myriad of functional consequences. Microglia are increasingly valued as critical players in neurological and psychiatric disorders.
Fatemeh Haghighi, PhD, lead author of the new work, said: “To fill this knowledge gap, we set out to characterize the DNA methylation landscape of human primary microglial cells and the factors that contribute to variations in blood microglial methyloma. “
DNA methylation is the primary form of epigenetic regulation, which determines the pattern by which genes are turned on or off under various circumstances over time.
The researchers studied microglial cells isolated from post-mortem human brain tissue from 22 donors of various ages, including 1 patient with schizophrenia, 13 with mood disorders and 8 controls without psychiatric disorders, collected from 4 regions of the brain. They analyzed the microglia using genome-wide methylation chips.
Not surprisingly, the microglia exhibited DNA methylation profiles distinct from other cells in the central nervous system. But less expected, Haghighi said, “we found that inter-individual differences rather than differences between regions of the brain had a much larger effect on the variability of DNA methylation.” In addition, exploratory analysis showed differences in the methylation profile of microglia from the brains of subjects with psychiatric disorders compared to controls.
John Krystal, MD, Editor-in-Chief of Biological Psychiatry, said of this work: “These promising data point to pathology of microglia, key immune cells in the brain, in the biology of depression. “