Scientists Attempt to Build a “Better Schizophrenic Mouse” – Is this a Worthwhile Effort?
March 25, 2013
Dr. Pam Osenkowski, Director of Science Programs
Last week, Science published an article called “Building a Better Schizophrenic Mouse” which highlighted a recent study that attempted to create a mouse model to mimic the cognitive defects seen in schizophrenia. While other researchers had previously recreated schizophrenia-like conditions in mice by creating irreversible lesions in a specific brain region, this new study more subtly reduced activity in this brain region while leaving it intact. Did this approach result in a “better” model? Does this new model really advance the field of schizophrenia research? Or should scientists focus their efforts on other approaches to learn more about this devastating mental disorder?
Schizophrenia is a complex mental disorder in which afflicted individuals may have a variety of symptoms. They may display “positive symptoms” -- psychotic behaviors not seen in healthy people like hallucinations, delusions, thought disorders, or movement disorders. They may display “negative symptoms” that disrupt normal behavior and emotions. Schizophrenic individuals may also display cognitive symptoms, those affecting thought, memory, and the ability to learn. Scientists are trying to better understand what causes schizophrenia and believe that genetics, environmental factors, and brain chemistry and structure play key roles.
In this recent study, the researchers focused their efforts on generating mice with cognitive defects like those seen in human schizophrenic individuals, and to do so, they used a method to reduce the activity of neurons in a specific brain region associated with schizophrenia. The researchers then monitored the animal’s behavior in various memory and learning tasks, including putting the mice in mazes, and compared that behavior to control mice whose brain activity was not altered. Results indicated that mice with reduced brain activity performed their tasks worse than control animals, and researchers concluded that altered activity in that specific brain region could be contributing to the cognitive symptoms seen in schizophrenic individuals.
After reading the article, I was left with a number of concerns, many of which are shared by other members of the scientific community.
- Just how well can mice mirror a complex psychiatric condition like schizophrenia?
- Are the memory and learning tests given to the animals translatable to memory and learning tests in people? Is putting a mouse in a maze the best way to study schizophrenia -- especially if this isn’t the way we study human cognition?
- Even if we see changes in the behavior of a mouse, should we assume that these are the same or similar cognitive changes we would see in schizophrenic patients?
- Can we really compare artificial brain activity reduction in a mouse with the natural reduction seen in human schizophrenic patients?
- While I appreciate that no animal model can fully mimic or recapitulate all aspects of human disorders, is it justifiable to call this a mouse model of schizophrenia when researchers are not able to follow some of the key symptoms of schizophrenia in mice – like hallucinations and delusions?
My concerns of this study, and others like it, are echoed by some members of the scientific community, despite the fact that these studies take place all of the time. According to the findings of a recent workshop on “Improving the Utility and Translation of Animal Models for Nervous System Disorders,” many researchers believe that current animal models of schizophrenia (and all other nervous system disorders) are not adequate. They wonder how useful the assays scientists use to test behavior and cognition in animals really are. Other people question what else can be done if animal models are not adequate.
One of the best suggestions that came from this workshop was to put more emphasis on human data by examining clinical and epidemiological research to better understand “what is wrong” in schizophrenia – and I agree. It is clear that the answers to questions about human conditions like schizophrenia will not be found in mouse models. It is time to find new tools and techniques to accelerate scientific advancement in schizophrenia research – and all other areas of research involving animal models. We must work with human-relevant models to better understand human health and well-being.
Improving the utility and translation of animal models for nervous system disorders-Workshop summary. (2013). The National Academies Press.
Parnaudeau, S., et al. (2013). Inhibition of mediodorsal thalalmus disrupts thalamofrontal connectivity and cognition. Neuron 77, 1151-1162
Underwood, E. (2013). Building a better schizophrenic mouse. ScienceNow.