Schizophrenia and aging could have a common biological basis

A team of scientists has discovered that the seniors and people with schizophrenia have a series of changes in the genetic activity of brain tissue “surprisingly” similar, suggesting that their cognitive impairment could have the same biological basis.

The details of the study, carried out by researchers from the Broad Institute of MIT and Harvard, Harvard Medical School and McLean Hospital, were published this Wednesday in the journal Nature.

The team analyzed gene expression in more than a million cells from post-mortem brain tissue from 191 people (with and without schizophrenia).

Thus, they discovered that, compared to healthy or young individuals, in people with schizophrenia and in elderly people without schizophrenia, astrocytes and neurons (two types of brain cells) reduced the expression of genes that support synapses (junctions between neurons). ).

They also saw that when neurons reduced the expression of certain genes related to synapses, astrocytes similarly changed the expression of other different genes that favor synapses, a series of coordinated changes that they called SNAP (Synaptic Neuronal and Astrocytic Program).

Even in healthy, young people, the expression of SNAP genes always increased or decreased coordinately in their neurons and astrocytes.

“These cell types do not act as independent entities, but are closely coordinated. The strength of those relationships took our breath away.”says Steve McCarroll, co-author and fellow at the Broad Institute.

The hallucinations and delusions caused by schizophrenia can be treated – at least in part – with specific medications, but the cognitive impairment caused by this pathology, which also occurs with aging, does not have effective treatments.

These findings suggest that cognitive changes in both conditions could involve similar cellular and molecular alterations in the brain, offering potential therapeutic clues.

The SNAP study

The brain works largely because neurons connect to other neurons at synapses.

The brain constantly forms new synapses and eliminates old ones. Scientists believe that new synapses help brains stay flexible, and several studies have shown that many genetic factors linked to schizophrenia involve genes that contribute to synapse function.

To find out more, in the new study, the team studied 1.2 million cells from nearly 200 people and found that when neurons increased the expression of genes that encode parts of synapses, astrocytes increased the expression of a different set. of genes involved in synaptic function.

These genes, which make up the SNAP program, included many previously identified risk factors for schizophrenia.

The team’s analyzes indicated that both neurons and astrocytes determine genetic vulnerability to the disease.

“Science has long known that neurons and synapses are important in the risk of schizophrenia, but by asking the question another way – asking which genes each cell type dynamically regulates – we found that astrocytes are likely also involved.” , says Emi Ling, a researcher at the Broad Institute and first author of the study.

To their surprise, the researchers also found that SNAP varied greatly even among people without schizophrenia, suggesting that SNAP could be involved in cognitive differences in healthy humans.

McCarroll now hopes to identify vital factors that positively influence SNAP to develop medications that help stimulate it and treat the cognitive disorders of schizophrenia or help older people maintain their cognitive flexibility as they age.

Additionally, the team is working to understand whether these changes are present in other conditions such as bipolar disorder and depression.