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| A new study from the University of Copenhagen shows that a targeted intervention in a specific type of brain cell can change behavior in mice with symptoms resembling schizophrenia. The researchers hope that this knowledge may eventually pave the way for more targeted treatments for conditions such as schizophrenia. Image Credit: Scientific Frontline / AI generated |
A specific type of brain cell is abnormally active in mice exhibiting behavior reminiscent of schizophrenia, according to a new study from the University of Copenhagen. By dampening the activity of these cells, researchers were able to restore the animals’ behavior—an insight that may pave the way for a new preventive treatment.
Difficulty completing everyday tasks. Failing memory. Unusually poor concentration.
For many people living with schizophrenia, cognitive challenges are part of daily life. Alongside well-known symptoms such as hallucinations and delusions, these difficulties can make it hard to live the life they want. That is why researchers at the University of Copenhagen are working to find ways to prevent such symptoms - and they may now be one step closer.
In a new study, researchers discovered that a specific type of brain cell is abnormally active in mice displaying schizophrenia-like behavior. When the researchers reduced the activity of these cells, the mice’s behavior changed.
“Current treatments for cognitive symptoms in patients with diagnoses such as schizophrenia are inadequate. We need to understand more about what causes these cognitive symptoms that are derived from impairments during brain development. Our study may be the first step toward a new, targeted treatment that can prevent cognitive symptoms,” says Professor Konstantin Khodosevich from the Biotech Research and Innovation Center at the University of Copenhagen, and one of the researchers behind the study.
Early Turning Point in the Brain May Enable Treatment
Schizophrenia stems from abnormal brain development, which can begin even before birth. Yet symptoms typically don’t appear until later in life.
“For a long time, the brain is able to compensate for developmental errors and maintain relatively normal function. But at some point, it’s like a chain snapping - the brain can no longer compensate, and that’s when symptoms emerge. Until that point, however, prevention should be possible,” says Katarina Dragicevic, one of the study’s first authors.
She investigated when this turning point occurs. By tracking brain development from the fetal stage to adulthood, she found that dramatic changes happen late in the brain’s development. Up until the transition from childhood to adolescence, molecular and functional changes in the brain were rather minor, likely explaining lack of symptoms before adolescence.
“Our study shows that until a specific point, brain development is largely unaffected by changes. The period leading up to that point may represent a treatment window where we can prevent functional impairment,” says Katarina Dragicevic.
Sleep Reveals Disruptions in Brain Function
The researchers have worked with mice carrying a specific genetic mutation known as “15q13.3 microdeletion syndrome.” In humans, this syndrome is associated with epilepsy, schizophrenia, autism, and other neurodevelopmental disorders.
“We know that sleep is often disrupted in people with psychiatric disorders, so we chose to use sleep as a behavioral marker—something we could observe. We examined both the mice’s behavior and the activity of a specific type of brain cell. Our findings show that one particular cell type is significantly affected in the test animals compared to healthy mice,” explains Katarina Dragicevic.
These rare brain cells are often overlooked because they make up only a tiny fraction of the brain’s total cell population. Nevertheless, they play a crucial role in regulating many brain functions.
A Potential Target for Treatment
The new study not only demonstrates a link between this specific type of brain cell and sleep - it also shows that the mice’s sleep patterns began to resemble those of healthy mice when researchers reduced the activity of the cell type in question.
“This means that this type of brain cell plays a critical role in sleep in mice with this syndrome. Using a technique called chemogenetics, we can reduce the activity of these cells and restore normal sleep patterns—potentially alleviating other psychiatric symptoms as well,” says Assistant Professor Navneet A. Vasistha from the Biotech Research and Innovation Center, and one of the study’s lead authors.
Although researchers are still far from being able to conduct similar tests in humans, the discovery marks an important first step on the long road of drug development.
“This cell type could potentially become a treatment target. We hope that in the future, patients will benefit from a therapy for cognitive disorders that doesn’t broadly affect brain cells, but is so precisely targeted that side effects can be minimized,” says Navneet A. Vasistha.
About the Study:
Multiple studies have previously shown that sleep disturbances are strongly associated with cognitive impairments in psychiatric disorders. Thus, the researchers propose that treating these rare cells in the brain might restore sleep and in turn alleviate at least some cognitive impairments in psychiatric patients.
The researchers investigated how a genetic mutation—15q13.3 microdeletion—affects brain development and function. The test mice carry the same mutation found in humans with increased risk of psychiatric disorders such as schizophrenia and autism.
To identify which brain cells are affected, the researchers combined several advanced methods. First, they mapped gene activity in over 120,000 individual brain cells from young and adult mice using a technique called single-cell RNA sequencing, which reveals which genes are turned on or off in each cell.
Next, they measured how specific brain cells respond to signals, focusing on a rare type of inhibitory brain cell called Sst_Chodl, which connects distant regions of the brain.
Finally, they tested how changes in these cells affect the mice’s sleep. By dampening the activity of Sst_Chodl cells using a pharmacological drug (a method called chemogenetics), they observed that sleep was restored to normal level.
Published in journal: Neuron
Authors: Andrea Asenjo-Martinez, Katarina Dragicevic, Wen-Hsien Hou, Attila Ozsvar, Nikolaj Winther Hansen, Ulrich Pfisterer, Rasmus Rydbirk, Samuel Demharter, Bente Emma Møller, Janina Gasthaus, Irina Korshunova, Jean-François Perrier, Marco Capogna, Navneet A. Vasistha, and Konstantin Khodosevich
Research Material: What Is: Schizophrenia
Source/Credit: University of Copenhagen
Reference Number: ns102825_01
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