Genes involved in immune system function have been found to have atypical expression patterns in the brains of people with several neurological and psychiatric conditions, including autism, in thousands of postmortem brain samples. According to a new study of
Of the 1,275 immune genes studied, 765 (60%) were found in adults with one of six conditions: autism, schizophrenia, bipolar disorder, depression, Alzheimer’s disease, or Parkinson’s disease showed either increased or decreased expression in the brain of Expression patterns vary by condition, suggesting that each has a different “signature,” said lead investigator Chunyu Liu, a professor of psychiatry and behavioral sciences at the Upstate College of Medicine in Syracuse, New York. said.
Immune gene expression could serve as a marker of inflammation, says Liu. Such immune activation, especially while in utero, has been associated with autism, but the mechanism is unclear.
“My impression is that the immune system doesn’t play such a minor role in brain disorders,” Liu said. “It’s a major player.”
Christopher Coe, professor emeritus of biopsychology at the University of Wisconsin-Madison, said in this study whether immune activation contributed to some condition, or whether the condition itself led to altered immune activation. said that it is impossible to determine from the work.
“Post-mortem brain studies are informative,” says Coe. “But it is inconclusive.”
L.iu and his team analyzed the expression levels of 1,275 immune genes in 2,467 postmortem brain samples, including 103 from autistic individuals and 1,178 from controls. Data were obtained from his two transcriptomics databases, ArrayExpress and Gene Expression Omnibus, as well as other previously published studies.
Autistic brains had an average of 275 genes whose expression levels differed from controls. Brains of Alzheimer’s disease patients had 638 differentially expressed genes, followed by brains with schizophrenia (220), Parkinson’s disease (97), bipolar disorder (58), and depression (27).
Expression levels in autistic males were more variable than in autistic female brains, whereas depressed female brains were more variable than depressed male brains. No gender differences were found in the four conditions.
Autism-related expression patterns resembled symptoms of neurological disorders such as Alzheimer’s and Parkinson’s more than other psychiatric disorders. By definition, a neurological condition must have known physical features in the brain, such as the loss of dopaminergic neurons characteristic of Parkinson’s disease. Researchers have found no such signs of autism.
“this [similarity] It just provides some additional direction to consider,” Liu said. “Maybe one day we will be able to understand the condition better.”
The survey results are molecular psychiatry in November.
T.Two genes, CRH and TAC1, are most commonly altered in the condition. CRH is downregulated in all conditions except Parkinson’s disease, and TAC1 is downregulated in all conditions except depression. Both genes influence the activation of microglia, immune cells in the brain.
Atypical microglial activation may be “derailing normal neurogenesis and synaptogenesis,” similarly disrupting neuronal activity across conditions.
Genes involved in astrocyte and synaptic function are similarly expressed in people with autism, schizophrenia, or bipolar disorder, a 2018 study of postmortem brain tissue found. However, the study found that the microglial gene was overexpressed only in autism.
People with more strongly upregulated immune genes may be in a “neuroinflammatory condition,” says Michael, professor and director of research in biological and precision psychiatry at the University of Copenhagen, Denmark. says Benross. He was not involved in this research.
“It may be interesting to identify these potential subgroups and of course offer more specific treatments,” says Benross.
Studies have shown that most of the expression changes observed in brain tissue samples do not appear in datasets of gene expression patterns in blood samples from individuals with the same condition. This “somewhat surprising” finding illustrates the importance of studying brain tissue, said Cynthia Schuman, professor of psychiatry and behavioral sciences at the MIND Institute at the University of California, Davis.
“If you want to know about the brain, you have to look at the brain itself,” says Schumann.
Liu and his team are creating cellular models to better understand whether inflammation is one of the contributing factors to the development of brain conditions.
Citing this article: https://doi.org/10.53053/UWCJ7407