Genes involved in the functioning of the immune system have atypical expression patterns in the brains of people with certain neurological and psychiatric disorders, including autism, according to a new study of thousands of post-mortem brain samples.
        Of the 1,275 immune genes studied, 765 (60%) were over- or down-expressed in the brains of adults with one of six disorders: autism, schizophrenia, bipolar disorder, depression, Alzheimer’s disease, or Parkinson’s disease. These expression patterns vary from case to case, suggesting that each one has unique “signatures,” said lead researcher Chunyu Liu, professor of psychiatry and behavioral sciences at Northern State Medical University in Syracuse, New York.
        According to Liu, the expression of immune genes can serve as a marker of inflammation. This immune activation, especially in utero, is associated with autism, although the mechanism by which it occurs is unclear.
        “My impression is that the immune system plays a significant role in brain diseases,” Liu said. “He’s a big player.”
        Christopher Coe, professor emeritus of biological psychology at the University of Wisconsin-Madison, who was not involved in the study, said it was not possible to understand from the study whether immune activation plays a role in causing any disease or the disease itself. this led to changes in immune activation. Job.
        Liu and his team analyzed the expression levels of 1,275 immune genes in 2,467 postmortem brain samples, including 103 people with autism and 1,178 controls. Data were obtained from two transcriptome databases, ArrayExpress and Gene Expression Omnibus, as well as from other previously published studies.
        The average level of expression of 275 genes in the brains of autistic patients differs from that in the control group; The brains of Alzheimer’s patients have 638 differentially expressed genes, followed by schizophrenia (220), Parkinson’s (97), bipolar (58), and depression (27).
        Expression levels were more variable in autistic men than in autistic women, and the brains of depressed women differed more than those of depressed men. The remaining four conditions showed no gender differences.
        The expression patterns associated with autism are more reminiscent of neurological disorders such as Alzheimer’s and Parkinson’s than other psychiatric disorders. By definition, neurological disorders must have known physical features of the brain, such as the characteristic loss of dopaminergic neurons in Parkinson’s disease. Researchers have yet to define this feature of autism.
        “This [similarity] just provides an additional direction that we need to explore,” Liu said. “Maybe one day we’ll understand pathology better.”
        Two genes, CRH and TAC1, were most frequently altered in these diseases: CRH was downregulated in all diseases except Parkinson’s disease, and TAC1 was downregulated in all diseases except depression. Both genes affect the activation of microglia, the brain’s immune cells.
       Coe said that atypical microglia activation could “impair normal neurogenesis and synaptogenesis,” similarly disrupting neuronal activity under a variety of conditions.
        A 2018 study of post-mortem brain tissue found that genes associated with astrocytes and synaptic function are equally expressed in people with autism, schizophrenia, or bipolar disorder. But the study found that microglial genes were only overexpressed in patients with autism.
       People with more immune gene activation may have a “neuroinflammatory disease,” said Michael Benros, study leader and professor of biological and precision psychiatry at the University of Copenhagen in Denmark, who was not involved in the work.
       ”It might be interesting to try to identify these potential subgroups and offer them more specific treatments,” Benroth said.
        The study found that most of the expression changes seen in brain tissue samples were not present in datasets of gene expression patterns in blood samples from people with the same disease. The “somewhat unexpected” finding shows the importance of studying the organization of the brain, said Cynthia Schumann, professor of psychiatry and behavioral sciences at the MIND Institute at UC Davis, who was not involved in the study.
       Liu and his team are building cellular models to better understand whether inflammation is a contributing factor to brain disease.
        This article was originally published on Spectrum, the leading autism research news website. Cite this article: https://doi.org/10.53053/UWCJ7407