ORLANDO, Fla. ― A normally silent area of the brain that is critical for learning and memory has been identified as a hotspot for abnormal electrical activity and could have implications for the treatment of Alzheimer’s disease and epilepsy, suggests early pre-clinical research presented at the American Epilepsy Society Annual Meeting.
Previous studies have detected the abnormal electrical activity called interictal spikes (IIS) in the temporal lobes of people with Alzheimer’s disease and epilepsy. But this is the first research to pinpoint that a specific region in the dentate gyrus — which is in the temporal lobe and part of the hippocampus — is the location of this activity, which most often occurs during rapid eye movement (REM) sleep. The research in mice also determined that inhibiting a single brain cell type in the medial septum — in front of the hippocampus — which is active during REM reduces this hyperactivity without affecting sleep.
“Until this research, we did not know where in the brain abnormal activity resides and why it often occurs during sleep,” said Christos Lisgaras, Ph.D., lead author of the study and a research scientist at NYU Langone Health and the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York. “Now that we know more about the areas that contribute to this activity, we can develop selective treatments that primarily target those areas. This research in mice is important because it’s not possible to do similar studies in humans.”
Researchers implanted electrodes in the brains of mice that had been engineered with three different mutations for Alzheimer’s disease and compared them to mice that did not have those mutations. The electrodes targeted the dentate gyrus and recorded brain activity from many areas of the brain at the same time. They detected IIS in all engineered mice but none in those without mutations.
They also inhibited a single brain cell type in the medial septum with chemogenetics, which uses a virus to infect the cell type targeted. The virus carries a protein that when activated lessens the activity of the cell type, reducing the electrical activity. This showed that the abnormal electrical activity can be reduced, which holds promise from a therapeutic standpoint.
“We know that fewer IIS are associated with better memory in people with Alzheimer’s disease and epilepsy and we believe a potential treatment could benefit both populations,” said Dr. Lisgaras. “For example, in the future, selective inhibition of the dentate gyrus early in the disease might benefit people with Alzheimer’s disease, although not all patients may be eligible for such intervention.”
There is a large overlap between Alzheimer’s disease and epilepsy, and patients with either of these conditions often experience seizures and have memory problems and abnormalities in the same brain structures. Additionally, they often have IIS, which has been linked to impaired memory. Patients with epilepsy are at high risk of developing Alzheimer’s disease and those with Alzheimer’s disease are at high risk of developing epilepsy.