Health
Schizophrenia and aging are both associated with decreased expression of the SNAP gene
Coordinated changes in gene expression activity in neurons and astrocytes in the brains of schizophrenia patients and older adults point to a possible common biological basis for the cognitive decline seen in both diseases.These findings are reported in a new paper Nature Paper titled “”Cooperative neuronal and astrocyte programs decline in aging and schizophrenia” Published by scientists at the Broad Institute, Harvard Medical School, and elsewhere.
The so-called synaptic neuron and astrocyte program (SNAP), in which synapses and neurons coordinate their expression, is observed in healthy brain tissue. Evidence suggests that reduced SNAP activity appears to be involved in aging and schizophrenia, and treatments and interventions to treat cognitive impairment in schizophrenia or maintain cognitive performance into old age may be warranted. This suggests that there is a possibility that it may become a target.
“Science has often focused on what genes each cell type uniquely expresses,” says Dr. Schmidt, director of genomic neurobiology at the Broad Center for Psychiatric Research and senior author of the study. said Dr. Steve McCarroll. “But machine learning analysis of many people's brain tissues and their data has helped us recognize a larger system. These cell types are not functioning as independent entities, but they are very We work closely with.”
Specifically, we analyzed postmortem brain tissue from 191 22-year-old donors.–(1997) found that both astrocytes and neurons synchronously reduced expression of genes that support synapses in older adults and patients with schizophrenia. Specifically, when neurons decreased the expression of synapse-related genes, astrocytes similarly changed the expression of genes that support synapses. “The strength of that relationship was breathtaking,” McCarroll said.
In this study, the scientists used mononuclear RNA sequencing to analyze gene expression in brain cells of 94 people with schizophrenia and 97 people without schizophrenia. They also developed computational tools to recognize and capture repeating multicellular gene expression patterns in the data. The SNAP genes that showed changes in expression levels included many genes previously associated with increased risk of schizophrenia.
This is additional information regarding genetic factors involved in schizophrenia. “Science has long known that neurons and synapses are important in the risk of schizophrenia,” said Dr. Emi Lin, a postdoctoral fellow in McCarroll's lab and lead author of the study. Stated. “[B]By framing the question differently, asking which genes each cell type dynamically controls, we found that astrocytes were also likely involved. ”
Although SNAP expression levels vary in healthy individuals, much of this variation is explained by age, with gene expression significantly reduced in many, but not all, older adults. This is true whether or not they have been diagnosed with schizophrenia, suggesting that changes in SNAP expression also influence cognitive performance with age.
As an immediate next step, the scientists are investigating whether altered SNAP expression also exists in other cognitive disorders such as bipolar disorder and depression. They also hope to study how SNAP expression affects learning and cognitive flexibility.
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