In a study that could potentially lead to the development of personalized treatments for Tourette syndrome, researchers have successfully bred mice that display similar behaviors and brain abnormalities as humans with the disorder. The study was conducted at Rutgers University-New Brunswick and was published in the Proceedings of the National Academy of Sciences.
Using a method called CRISPR/Cas9 DNA editing, scientists were able to selectively change the DNA of living organisms. They inserted the same genetic mutations that are found in humans with Tourette disorder into the genes of mouse embryos. After the mice were born, the scientists observed their behavior and compared it to the behavior of littermates that did not have the gene mutation. The mutations that were inserted were discovered by some members of the research team who have been studying genetic factors in Tourette disorder for over ten years.
The researchers believe that these findings show that these mice are a valuable tool for studying the neurological aspects of Tourette disorder.The study of the biology of Tourette disorder is essential in order to develop new medications and test their effectiveness. According to co-senior author Jay Tischfield, there are currently no medications specifically designed for Tourette disorder. Repurposing other drugs has not been successful due to the many side effects. Tischfield also noted that the lack of an animal model has been a significant obstacle in testing new or existing medications. Tourette disorder is a condition that affects individuals of all ages and is characterized by a dysfunction in the nervous system.Tourette’s syndrome is a condition characterized by sudden, involuntary movements or sounds known as tics. These tics can range from mild to severe and can be disabling for some individuals.
Although Tourette’s syndrome does not affect lifespan, it can have a negative impact on the daily lives of those affected and the people around them. According to the Centers for Disease Control and Prevention, approximately 1 in 162 children have Tourette’s syndrome, but this number may actually be higher.
A group of researchers used cameras to record the actions of genetically engineered mice and utilized machine learning, a form of artificial intelligence, to analyze the data.The study showed that individuals with Tourette disorder displayed two main characteristics similar to people with the disorder. They engaged in repetitive motor behaviors or tics and had what neuroscientists refer to as “sensorimotor gating deficits,” which is a brain process that filters out unnecessary stimuli. Cara Nasello, a research associate in the Departments of Genetics and Cell Biology and Neuroscience and the study’s first author, explained that the gating deficits in individuals with Tourette syndrome can be seen as a struggle in processing sensory information. For example, a person without the disorder might listen to a series of sounds and be able to differentiate them easily.A person who hears a car horn honking repeatedly may not be startled after the first honk because their brain can connect the subsequent sounds to the first one. However, someone with Tourette’s syndrome may be startled by each separate sound, especially if the volume increases. The genetically modified mice reacted similarly to humans with the disorder, showing a startle response to each individual tone that was part of a pattern. This research was conducted in collaboration with Miriam Bocarsly from the Department of Pharmacology, Physiology, and Neuroscience at Rutgers New Jersey Medical School.Gene mutations have been found to affect the levels of dopamine in the brain. When mice were given a drug that changes dopamine levels, similar to how humans with Tourette disorder are treated, their processing deficits and repetitive behaviors were reduced. According to Max Tischfield, an assistant professor at Rutgers School of Arts and Sciences, this is because the gene mutation altered the neural circuitry in the mice’s brains.changes are modifying the way a neurotransmitter such as dopamine, which plays a crucial role in human cognition and movement, allows communication between brain cells in mice.”
The researchers recognized the significant contributions of families affected by Tourette disorder, who have generously donated genetic samples to the research group over the last 15 years.
“These families selflessly contributed to advancing the field,” stated Gary Heiman, a co-senior author of the study and a professor in the Department of Genetics, who enlisted families with Tourette disorder from around the globe.The researchers are working on improving their methods for capturing and storing blood and genetic samples. Their goal is to gain a better understanding of Tourette’s syndrome and develop more effective treatments for current and future sufferers. The techniques they are using could also be beneficial for studying other complex disorders, such as autism and schizophrenia. Additionally, the researchers hope that their progress will encourage more scientists to study Tourette’s syndrome, even though there is still much to learn about it.Max Tischfield mentioned that people often feel overwhelmed and unsure of how to even begin understanding such a complex disorder. He added that using the mice, they are not only able to scratch the surface but can also delve deeper into the issue.
