0
0
A collaborative effort by researchers from the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital has uncovered strikingly similar changes in gene activity in brain tissue from individuals with schizophrenia and from older adults. These findings suggest a common biological basis for cognitive impairment in both conditions.
Published in the journal Nature, the study involved analyzing gene expression in over a million individual cells from postmortem brain tissue collected from 191 individuals. The researchers, led by co-senior authors Steve McCarroll and Sabina Berretta, found that in both individuals with schizophrenia and older adults without the condition, two types of brain cells — astrocytes and neurons — exhibited reduced expression of genes supporting synapses, the junctions between neurons. Moreover, the study revealed synchronized gene expression changes in these two cell types, which the team termed the Synaptic Neuron and Astrocyte Program (SNAP).
McCarroll, an institute member at the Broad Institute, emphasized the significance of recognizing this larger system of coordinated gene expression between different cell types in the brain. The study’s first author, Emi Ling, highlighted the importance of studying tissue samples from a large number of individuals to detect the coordination between astrocytes and neurons in schizophrenia and aging.
Schizophrenia, characterized by hallucinations, delusions, and cognitive decline, shares similarities with cognitive changes observed in aging. The study’s findings suggest that these cognitive changes in both conditions may involve similar cellular and molecular alterations in the brain.
By analyzing single-nucleus RNA sequencing data, the researchers observed that when neurons increased the expression of genes related to synapses, astrocytes also upregulated a distinct set of genes involved in synaptic function, forming the SNAP program. Importantly, SNAP variation was observed even among individuals without schizophrenia, with much of this variation explained by age, indicating its potential involvement in cognitive differences in healthy individuals.
McCarroll hopes that understanding SNAP better could lead to the identification of life factors positively influencing it and the development of medicines to stimulate SNAP, potentially aiding in treating cognitive impairments in schizophrenia and age-related cognitive decline.
Moving forward, the researchers aim to investigate if similar changes are present in other conditions such as bipolar disorder and depression. They also plan to explore the extent to which SNAP appears in other brain regions and its impact on learning and cognitive flexibility.
