In the brain, neurons use tightly controlled chemical and electrical signals to communicate with one another in complex networks. Low levels of a protein that facilitates these signals are associated with Alzheimer’s-related memory problems in a mouse model of the disease, according to NIH-supported scientists at the University of California, San Francisco. Restoring levels of the protein, known as Nav1.1, improved learning and memory in the mice and increased lifespan.
The investigators measured brain-wave activity in mouse models with high levels of beta-amyloid, a pathological hallmark of Alzheimer’s, in the brain. They found that specific abnormalities occurred during periods of reduced gamma-wave oscillations, a type of brain wave involved in regulating learning and memory. They further found that Nav1.1 levels in specialized nerve cells known as parvalbumin cells were decreased in these mice, suggesting an association between reduced Nav1.1 levels and abnormal brain-wave activity. The mice also had impaired memory and decreased lifespan compared with normal mice. However, when Nav1.1 levels were restored, brain-wave activity returned to normal, memory improved, and lifespan increased, despite the continued presence of high levels of beta-amyloid in the brain.
Further research is needed to see if these findings might extend from mice to humans. But, these observations provide important clues about a potential mechanism involved in network and cognitive dysfunctions. Gamma wave alterations like those addressed in this Alzheimer’s study also occur in other neurological disorders, including epilepsy, autism, and schizophrenia, suggesting that these findings may have implications for these conditions as well.
Reference: Verret L., et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149: 708-721, April 27, 2012.