summary: A new study reveals common cellular and molecular changes in the brains of schizophrenia patients and older adults, pointing to a common biological basis for cognitive impairment in these groups.
The study analyzed gene expression in more than 1 million cells from 191 people and found a coordinated decline in genes that support synaptic connections between neurons and astrocytes, called the synaptic neuron-astrocyte program (SNAP). revealed. This synchronization indicates a tightly coordinated system that influences brain function, with potential implications for understanding and treating cognitive decline in schizophrenia and aging.
The discovery of SNAP provides insight into synaptic dynamics in the brain and raises hopes for identifying interventions to preserve cognitive function.
Important facts:
- Common biological basis: Similar gene expression changes in astrocytes and neurons were found in both schizophrenia patients and older adults, suggesting common mechanisms of cognitive decline.
- Role of SNAP: The synaptic neuron and astrocyte program (SNAP) reflects the health of synapses in the brain and its expression declines with age, contributing to cognitive differences between healthy individuals.
- Potential new treatments: Understanding the dynamics of SNAP may lead to strategies to enhance synaptic health and provide new avenues to address cognitive impairments associated with schizophrenia and aging.
sauce: Broad Institute
Researchers at MIT and Harvard’s Broad Institute, Harvard Medical School, and McLean Hospital have discovered a strikingly similar set of changes in gene activity in the brain tissue of schizophrenia patients and older adults.
These changes suggest a common biological basis for the cognitive impairments that are common in people with schizophrenia and in older adults.
In a study published in Naturethe research team describes how they analyzed gene expression in more than 1 million individual cells taken from postmortem brain tissue from 191 people.
Researchers found that in schizophrenia patients and older adults without schizophrenia, two types of brain cells, called astrocytes and neurons, have fewer connections between neurons, called synapses, than in healthy people and younger people. They found that the expression of genes that support this was reduced.
They also found that changes in gene expression in the two cell types were tightly synchronized. As neurons reduced the expression of specific genes associated with synapses, astrocytes similarly changed the expression of a distinct set of genes that support synapses.
The research team called this coordinated series of changes the synaptic neuron and astrocyte program (SNAP). Even in healthy young people, SNAP gene expression is constantly increased or decreased in a coordinated manner in neurons and astrocytes.
“Science often focuses on what genes each cell type uniquely expresses,” says Steve McCarroll, co-senior author of the study and a researcher at the Broad Institute. .
“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 rather We work closely together, and the strength of that relationship has taken our breath away.”
Schizophrenia is well known for causing hallucinations and delusions, which can be treated, at least in part, with drugs. But it also causes debilitating cognitive decline, which has no effective treatment and is common in aging.
New findings suggest that cognitive changes in both conditions may involve similar cellular and molecular changes in the brain.
“To detect the cooperation between astrocytes and neurons in schizophrenia and aging, we needed to study tissue samples from a very large number of people,” said co-senior author of the study and a professor at Harvard Medical School. Associate Professor Sabina Beretta said. A researcher in the field of mental illness.
“We would like to express our gratitude to all the donors who have chosen to donate their brains to research and want to dedicate this research to help those suffering from brain disorders.”
McCarroll is chair of the Department of Genomic Neurobiology at the Broad University Stanley Psychiatric Research Center and a professor at Harvard Medical School. Beretta is also the director of the Harvard Brain Tissue Resource Center (HBTRC), which provided tissue for the study. Emi Lin, a postdoctoral fellow in McCarroll’s lab, is the study’s lead author.
SNAP Insights
The main reason the brain works is that neurons connect to other neurons at synapses, where they pass signals to each other. The brain constantly forms new synapses and prunes old ones.
Scientists believe that new synapses help our brains remain flexible, and research (including previous efforts by scientists in McCarroll’s lab and an international consortium) has shown that the integration Many genetic factors associated with ataxia have been shown to involve genes that contribute to synaptic function.
In a new study, McCarroll, Berretta and colleagues used single-nuclear RNA sequencing, which measures gene expression in individual cells, to better understand how the brain naturally differs from person to person. They analyzed 1.2 million cells. 94 people had schizophrenia and 97 people did not have schizophrenia.
They found that when neurons promoted expression of genes encoding parts of synapses, astrocytes increased expression of a set of different genes involved in synaptic function.
These genes comprising the SNAP program included many previously identified risk factors for schizophrenia. The research team’s analysis showed that both neurons and astrocytes form a genetic vulnerability to this condition.
“Science has long known that neurons and synapses are important in schizophrenia risk, but by framing the question differently, asking which genes each cell type dynamically controls, This indicates that astrocytes are also likely involved,” Lin said.
Surprisingly, the researchers also found that SNAP differed significantly among people without schizophrenia, suggesting that SNAP may be involved in cognitive differences in healthy humans. did.
Much of this variation is explained by age. SNAP has declined significantly for many, but not all, older adults, including both those with schizophrenia and those without.
A better understanding of SNAP could help us treat the cognitive deficits in schizophrenia, identify lifestyle factors that positively impact SNAP, and stimulate SNAP as a way to maintain cognitive flexibility in schizophrenia. McCarroll says it may be possible to develop a drug to do just that. Year.
In the meantime, McCarroll, Beretta, and their team are working to understand whether these changes also exist in other conditions such as bipolar disorder and depression. They also aim to understand the extent to which SNAP appears in other brain regions and how it affects learning and cognitive flexibility.
Funding: This research was supported by the Stanley Family Foundation, the Simons Collaboration on Plasticity and Brain Aging, the National Institute of Mental Health and the National Human Genome Research Institute of the National Institutes of Health.
About this aging and schizophrenia research news
author: Alessandra DiCorato
sauce: Broad Institute
contact: Alessandra DiCorato – Broad Institute
image: Image credited to Neuroscience News
Original research: Open access.
“Cooperative neuronal astrocyte programs decline in aging and schizophreniaWritten by Steve McCarroll et al. Nature
abstract
Cooperative neuronal astrocyte programs decline in aging and schizophrenia
The human brain changes from person to person and over time. Such changes are not yet understood in cellular terms. Here, we discuss the relationship between cortical neurons and cortical astrocytes in people.
We used mononuclear RNA-seq to analyze the prefrontal cortex of 191 human donors aged 22 to 97 years, including healthy people and people with schizophrenia.
Latent factor analysis of these data revealed that in people in whom cortical neurons more strongly express genes encoding synaptic components, cortical astrocytes express distinct genes with synaptic function and synaptic membranes supplied by astrocytes. It has been revealed that the gene for synthesizing the component cholesterol is more strongly expressed. We call this relationship the synaptic neuron and astrocyte program (SNAP).
In schizophrenia and aging (two conditions that involve decreased cognitive flexibility and plasticity), cells that are disconnected from SNAP, namely astrocytes, glutamatergic (excitatory) neurons, and GABAergic (inhibitory) All neurons showed decreased SNAP expression to a corresponding extent.
Both distinct astrocytic and neuronal components of SNAP were implicated in genes with a strong concentration of genetic risk factors for schizophrenia. SNAP varies quantitatively even among healthy individuals of the same age, may underlie many aspects of normal human individual differences, and is an important point at which multiple types of pathophysiology converge. There is a possibility.
