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    Home > Biochemistry News > Biotechnology News > Nature Genetics: Can transcriptional maps of microglia guide research in brain diseases?

    Nature Genetics: Can transcriptional maps of microglia guide research in brain diseases?

    • Last Update: 2022-01-26
    • Source: Internet
    • Author: User
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    It is well known that certain small differences in DNA sequence may increase a person's risk of developing Alzheimer's disease or Parkinson's disease
    .
    Recently, researchers at the Icahn School of Medicine at Mount Sinai found that some of the differences may work by altering the activity of microglia

    .

    The researchers analyzed microglia in different regions of the brain of deceased patients with neuropsychiatric and neurodegenerative diseases
    .
    Their findings, published in the journal Nature Genetics, support the idea that microglia may play a key role in some cases of brain disease, while also providing potential guidelines for future research

    .

    The research was led by Katia de Paiva Lopes, PhD, Gijsje Snijders, PhD, and Jack Humphrey, PhD, who work in the labs of Towfique Raj, PhD, associate professor of neuroscience, and Lotje D.
    de Witte, PhD, assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai

    .

    Microglia, shaped like octopuses, are found throughout the brain
    .
    In the nearly 100 years since they were first discovered, scientists believed that these cells acted both as the brain's immune system to fight infection and as a scavenger

    .
    They also believe that microglia play a passive role in brain disease, rather than a pathogenic role

    .

    Recently, this view has begun to change
    .
    Experiments in rodents, for example, suggest that microglia may actively shape how the brain is wired

    .
    Meanwhile, genomic studies have uncovered a potential link between microglia and risk of brain disease, as certain DNA sequences are linked to diseases such as Alzheimer's and multiple sclerosis

    .
    However, it has been difficult to correlate these results with specific genes

    .

    In this study, scientists used advanced genomics techniques to delve into the multiple roles that microglia may play in the brain
    .
    To do so, they created the largest high-resolution microglial genome map of its kind

    .
    They extracted microglia from human brain tissue samples and carried out a series of gene activity experiments

    .

    Specifically, they obtained 255 samples from 100 donors, representing 4 different brain regions
    .
    The donors, from brain tissue repositories in the Netherlands and the United States, ranged in age from 21 to 103, with an average age of about 73

    .
    Ninety-six samples were from control donors, while the rest were from donors diagnosed with neurological or psychiatric disorders

    .

    Overall, these findings support both previous findings and new findings
    .
    For example, the gene activity of microglia varies with age or in different regions of the brain, underscoring the different roles that microglia play throughout the brain and at different stages of life

    .
    In addition, aging appears to alter the activity of genes involved in the immune system

    .

    The results further suggest that microglia may be involved in some cases of Alzheimer's disease and Parkinson's disease, as well as other diseases, including multiple sclerosis, schizophrenia and bipolar disorder
    .
    They mapped expression and splicing quantitative trait loci, showing that many neurological disease susceptibility loci are mediated by gene expression or splicing in microglia

    .

    Finally, the researchers identified two new genes that may be involved in brain disorders
    .
    A gene called USP6NL has been linked to Alzheimer's disease, while another called P2RY12 has been linked to Parkinson's disease

    .
    The authors believe that transcriptome profiling can provide a comprehensive guide to fully understand the roles that microglia may play in both health and disease states

    .

    ###

    Lopes, KdP, Snijders, GJL, Humphrey, J.
    et al.
    Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies.
    Nat Genet (2022).
    https://doi.
    org/10.
    1038/s41588-021 -00976-y


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