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Changes in Same Brain Cells May Underlie Cognitive Impairment in Both Schizophrenia and Aging
An Ivy League research team has proposed that a similar collection of changes in brain tissue gene activity may underlie the cognitive impairment that often accompanies schizophrenia and aging. Authors from the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard published their findings in Nature.
Study authors utilized single-nucleus RNA sequencing to analyze 1.2 million prefrontal cortex cells from 191 human donors, 94 diagnosed with schizophrenia and 97 without. Compared to healthy people, authors found that in participants with schizophrenia and older adults without schizophrenia, “astrocytes and neurons reduced their expression of genes that support the junctions between neurons called synapses, compared to healthy or younger people.”
“Science has long known that neurons and synapses are important in risk for schizophrenia, but by framing the question a different way—asking what genes each cell type regulates dynamically—we found that astrocytes too are likely involved,” said Emi Ling, PhD, study first author and a postdoctoral researcher in McCarroll’s Broad Institute lab.
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Additionally, researchers observed closely synchronized changes in gene expression in both cell types. When neurons exhibited a decrease in the expression of certain genes related to synapses, the process was closely followed by a similar decrease in astrocyte gene expression, distinct from that of neurons but also involved in synapses support.
“Science often focuses on what genes each cell type expresses on its own,” said Steve McCarroll, PhD, co-senior study author and an institute member. “But brain tissue from many people, and machine-learning analyses of those data, helped us recognize a larger system. These cell types are not acting as independent entities, but have really close coordination. The strength of those relationships took our breath away.”
The research team has dubbed this coordinated set of changes the Synaptic Neuron and Astrocyte Program (SNAP). The observation of SNAP supports previous findings from McCarroll’s and others’ previous research that many genetic factors tied to schizophrenia are linked to genes that underlie synaptic function.
McCarroll’s team will expand this research to see if SNAP might also be present in other psychiatric conditions.
This study was supported by the Stanley Family Foundation, the Simons Collaboration on Plasticity and the Aging Brain, the National Institute of Mental Health, and the National Human Genome Research Institute at the National Institutes of Health.
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