New Research Discovers Brain Proteins’ Link to Movement, Anxiety, and Memory in Mice, Offering Potential for Schizophrenia Treatments
Researchers at Ohio State University have discovered a physical interaction between two brain proteins, MAP6 and Kv3.1, that plays a crucial role in controlling movement, anxiety, and memory in mice. The study, published in the journal Molecular Psychiatry, highlights the significance of these proteins in maintaining these functions and suggests that understanding their interaction could open new avenues for the development of schizophrenia treatments.
Schizophrenia is a complex mental disorder characterized by symptoms such as delusions, hallucinations, movement problems, and memory impairments. Previous studies have identified MAP6 and Kv3.1 as risk genes for schizophrenia based on dysfunction observed in brain tissue.
The research team, led by Chen Gu, associate professor of biological chemistry and pharmacology at Ohio State University, found that the two proteins bind to each other under normal conditions in multiple regions of the brain. Disruption to this interaction resulted in behavioral symptoms commonly associated with schizophrenia, including hyperactivity, reduced risk avoidance, and memory problems.
“These two proteins are seemingly unrelated, and our study has provided a link between them that wasn’t recognized before,” said Gu. “We’re hopeful that getting a better understanding of this mechanism could help in the long run to find a new treatment that could benefit patients with schizophrenia.”
In their experiments, the researchers disrupted the proteins’ ability to bind to each other in specific brain regions in mice. They found that disruption in the amygdala, which processes emotions, led to a decrease in risk avoidance. Blocking the proteins’ attachment in the hippocampus, responsible for learning and memory, resulted in hyperactivity and diminished recognition of a familiar object.
Although some behavioral changes observed in these experiments differed from the complete absence of one or both genes in mice, the research provided valuable insights into the brain regions where the proteins’ interactions or lack thereof have the most significant impact on behavior.
The researchers also conducted biochemistry and cell biology experiments to determine how the proteins bind and how this connection affects their positioning inside neurons. The results showed that MAP6 stabilizes the Kv3.1 channel in specific interneurons, helping regulate brain signals. A decrease in MAP6 expression significantly reduced Kv3.1 levels in these interneurons.
The combined findings suggest that when the proteins fail to bind properly, there is an insufficient amount of Kv3.1 available to maintain interneurons’ signal-control function. This leads to an imbalance of neural inhibition and excitation in affected brain regions and related negative behavioral symptoms. Targeting these types of interneurons, which generate nerve impulses at high frequencies, could be a key therapeutic approach for schizophrenia.
The researchers plan to further investigate the relationship between social behavior in mice and the functions of these proteins in the prefrontal cortex, a brain region involved in decision-making and planning.
The study was supported by grants from the National Institutes of Health. Additional co-authors of the study include researchers from Ohio State University and the Grenoble Institut Neurosciences in France.
Overall, this research highlights the importance of understanding the interaction between brain proteins in order to develop effective treatments for schizophrenia. Further exploration of these proteins’ functions and their impact on neural circuits could potentially lead to significant advancements in schizophrenia treatment strategies.