Unsociable Mice Were Looking for Friends: New Research Could Help Autistic People
Laboratory mice that avoided contact with others started socialising after just two weeks of therapy, and their improved social behaviour persisted even after the treatment ended. Research led by Dr Jakub Szabó from the Institute of Medical Physics and Biophysics and the Institute of Molecular Biomedicine at the Faculty of Medicine, Comenius University, contributes to the broader understanding of the causes of autism spectrum disorders and potential therapies. An article on this research was published last year in the prestigious journal Molecular Psychiatry, part of the Nature Publishing Group. For his work, Dr Szabó received the Ľudmila Sedlárová Rabanová Prize.
Jakub Szabó, together with a team of experts from the Faculty of Medicine at Comenius University, is investigating how autism spectrum disorders develop and exploring possible treatments. “Autism spectrum disorders are highly heterogeneous, both in their manifestations and their origins. We know that approximately 1% of autistic individuals suffer from a genetic deficiency of the protein SHANK3, which plays a crucial role in the brain by forming a structural ‘scaffolding’ between synapses. Alongside other proteins, it strengthens synaptic connections. This is why we focused our research on mice that also lack this protein,” he explains.
Unsociable Mice
One of the most significant challenges faced by autistic individuals is difficulty in forming social connections. Many struggle with social situations, have trouble communicating, reading between the lines, and understanding the intentions of others. These difficulties often compound other symptoms of the disorder. Mice with a SHANK3 deficiency exhibit a similar pattern of behaviour. “They possess an autism-like phenotype, which is expressed by avoiding contact with other mice,” says Jakub Szabó. The researchers assessed the social behaviour of these SHANK3-deficient mice using various behavioural methods. “In our test, a mice were placed with an unfamiliar ‘social partner’ while we observed how much time they spent interacting versus avoiding contact. If avoidance was significantly more frequent, we classified the mouse as having reduced sociability. Our findings confirmed that SHANK3-deficient mice displayed a profound social deficit. They showed no interest in interacting with others, often avoiding them, running away, or freezing—a defensive reaction sometimes seen in mice under threat. In contrast, control mice which were genetically intact exhibited typical sociable behaviour,” Szabó describes.
How to Change Antisocial Behaviour?
The next step was to explore how to “repair” these mice by identifying a substance that could improve their sociability. The researchers chose oxytocin, a hormone that has been extensively studied in relation to autism spectrum disorders. “We know that some autistic individuals have lower levels of oxytocin in their blood. Oxytocin itself has a well-documented prosocial effect. So, we decided to administer oxytocin to our mice in specific doses over an extended period,” explains Jakub Szabó. For 30 days, the mice received oxytocin intranasally (through the nose) - when their noses were tickled their reflex was to inhale the precise dose. The researchers then assessed their social behaviour after two and four weeks, as well as other traits such as anxiety-like behaviour, repetitive actions, and cognitive functions, including short-term and long-term memory. They aimed to determine whether oxytocin influenced these additional areas.
They were pleased with the results. Previously solitary, unsociable mice started “making friends” with others. “The effect was remarkable. After just two weeks, the mice’s social deficits normalised, and their sociability levels matched those of control mice. Compared to SHANK3-deficient mice that did not receive oxytocin, the treated mice’s interaction rates nearly doubled,” says Szabó.
Even more encouraging was the fact that the positive effects lasted for at least four weeks after the treatment ended, suggesting that prolonged stimulation was enough to activate the mice’s internal mechanisms. Oxytocin also helped reduce repetitive behaviours and anxiety-related symptoms.
The Road to Human Therapy
Although the results in mice are encouraging, the path to a viable treatment for autistic people remains long. According to Jakub Szabó, it is not as simple as administering oxytocin via a nasal spray to instantly improve sociability or eliminate repetitive behaviours. The reasons for this remain unclear. “As we mentioned, patients with autism are highly heterogeneous. However, I firmly believe that future research into human treatment will continue in this direction. It will be necessary to identify individual differences in autistic patients—potentially at the genetic level—and develop personalised therapies.”
Interdisciplinarity is Key
Jakub Szabó has followed an unusual academic and professional path. He graduated in psychology from the Faculty of Arts at Comenius University, earned a PhD in neuroscience at the Faculty of Medicine, worked on an internship at New York University, as well as a data analyst for ESET. He is currently based at the Institute of Medical Physics and Biophysics at the Faculty of Medicine of Comenius University. In 2024, he was awarded the Ľudmila Sedlárová Rabanová Prize for an outstanding publication in the biological sciences at the Faculty of Natural Sciences. He believes that interdisciplinary collaboration is essential today. “In the 21st century, we cannot afford to work in isolated fields. The challenges we face are complex, and we need comprehensive solutions,” he says.
According to him, many people at Comenius University are open to collaboration. “I have been fortunate to meet like-minded people during my studies and I continue meeting them now as a researcher at our university. Professor Heretik Jr. and Associate Professor Hajdúk at the Faculty of Arts guided me towards neuropsychology, while Professor Daniela Ostatníková encouraged me, as a non-medical graduate, to pursue a doctorate at the Faculty of Medicine. She also leads the Academic Centre for Autism Research, with which we frequently collaborate. My PhD supervisor, Professor Peter Celec, is a meticulous man of principles and values interdisciplinarity while conducting cutting-edge interdisciplinary research. Additionally, we have long-standing cooperation with Professor Ľubomír Tomáš from the Department of Genetics at the Faculty of Natural Sciences.”
True Value is Intangible
The financial award associated with the Ľudmila Sedlárová Rabanová Prize will be reinvested into further research. Szabó sees the award as confirmation that his work is meaningful. “The greatest reward is not the prize itself, but the recognition that our research matters. Since receiving the award, I have had insightful discussions with fellow experts, allowing us to plan future projects and collaborations. I have also had engaging conversations with the general public, which helps keep me grounded. We have many brilliant scientists with great ideas and strong motivation to pursue research. I truly believe that doing science in Slovakia with such people makes sense.”
Barbora Tancerová