Microglial methylation 'landscape' in human brain
Profiles differ across age, disease state, brain region

Date:
December 28, 2021
Source:
Elsevier
Summary:
Recent studies have shown variation in the gene-expression profile
and phenotype of microglia across brain regions and between
different age 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 microglia from human brain.



FULL STORY ==========================================================================
In the central nervous system, microglial cells play critical roles in development, aging, brain homeostasis, and pathology. Recent studies have
shown variation in the gene-expression profile and phenotype of microglia across brain regions and between different age 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 microglia from human brain.


==========================================================================
The study appears in Biological Psychiatry, published by Elsevier.

Microglia, the brain's own immune cells, were once thought of as a
homogenous population that was either "activated" or "inactivated," with
either pro- inflammatory or neuroprotective effects. But the cells are now recognized to have a vast array of phenotypes depending on environmental conditions with myriad functional consequences. Microglia are increasingly appreciated as critical players in neurologic and psychiatric disorders.

Fatemeh Haghighi, PhD, senior author of the new work, said: "To address
this gap in knowledge, we set out to characterize the DNA methylation
landscape of human primary microglia cells and factors that contribute
to variations in the microglia methylome." DNA methylation is the main
form of epigenetic regulation, which determines the pattern of which
genes are being turned "on" or "off" in various circumstances over time.

The researchers studied isolated microglia cells from post-mortem human
brain tissue from 22 donors of various age, including 1 patient with schizophrenia, 13 with mood disorder, and 8 controls with no psychiatric disorder, taken from 4 brain regions. They analyzed the microglia using genome-scale methylation microarrays.

Unsurprisingly, microglia showed DNA methylation profiles that were
distinct from other cells in the central nervous system. But less
expected, said Haghighi, "we found that interindividual differences
rather than brain region differences had a much larger effect on the
DNA methylation variability." In addition, an exploratory analysis
showed differences in the methylation profile of microglia from brains
of subjects with psychiatric disorders compared to controls.

John Krystal, MD, Editor of Biological Psychiatry, said of the work,
"These promising data point to pathology of the microglia, key
immune cells of the brain, in the biology of depression." special
promotion Explore the latest scientific research on sleep and dreams
in this free online course from New Scientist -- Sign_up_now_>>> academy.newscientist.com/courses/science-of-sleep-and-dreams ========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Lot D. de Witte, Zhaoyu Wang, Gijsje Snijders, Natalia Mendelev,
Qingkun
Liu, Marjolein Sneeboer, Marco P.M. Boks, Yongchao Ge, Fatemeh
Haghighi.

Contribution of age, brain region, mood disorder
pathology, and interindividual factors on the methylome
of human microglia.. Biological Psychiatry, 2021; DOI:
10.1016/j.biopsych.2021.10.020 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211228135848.htm

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