Researchers at the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital have made a significant discovery regarding gene activity in individuals with schizophrenia and older adults. The findings indicate a shared biological foundation for the cognitive decline often observed in both demographics.
The team, as outlined in a publication in Nature, conducted a thorough analysis of gene expression in over one million individual cells from postmortem brain tissue from 191 subjects. They observed that individuals with schizophrenia and older adults without the condition exhibited a decrease in gene expression related to synapse support in two specific brain cell types – astrocytes and neurons – in comparison to younger and healthy individuals. Moreover, the researchers identified synchronized changes in gene expression in these two cell types; when neurons reduced the expression of select genes associated with synapses, astrocytes also displayed alterations in the expression of a different set of genes supporting synapses.
The collective series of changes observed were termed the Synaptic Neuron and Astrocyte Program (SNAP). Interestingly, even in young and healthy individuals, the expression of SNAP genes consistently increased or decreased in a coordinated manner in both neurons and astrocytes.
“While scientific focus often centers on individual genes expressed by specific cell types, the analysis of brain tissue from numerous subjects, along with machine learning algorithms, allowed us to identify a broader system at play. These cell types exhibit intricate coordination, a revelation that left us astounded,” remarked Steve McCarroll, co-senior author of the study and a member of the Broad Institute.
Schizophrenia is recognized for inducing hallucinations and delusions, which can be mitigated to some extent with medications. However, the condition also leads to severe cognitive deterioration, with no effective treatments available, and this decline is a common feature of aging. The recent findings propose that the cognitive changes in both scenarios may involve comparable cellular and molecular modifications in the brain.
“In order to uncover the coordination between astrocytes and neurons in schizophrenia and aging, a large number of individuals’ tissue samples were necessary for study,” noted Sabina Berretta, co-senior author of the study, an associate professor at Harvard Medical School, and a specialist in psychiatric disorders. “We extend our gratitude to all brain donors who contributed to research efforts aimed at aiding individuals grappling with brain disorders.”
McCarroll serves as the director of genomic neurobiology for the Stanley Center for Psychiatric Research at the Broad and is also a professor at Harvard Medical School. Berretta heads the Harvard Brain Tissue Resource Center (HBTRC), which supplied tissue for the research. The study’s lead author, Emi Ling, is a postdoctoral researcher in McCarroll’s laboratory.
Insights on SNAP
The brain’s functionality heavily relies on the connections established between neurons at synapses, where signals are exchanged.