How seizures may lead to memory loss

Researchers have discovered a mechanism that can explain how even relatively infrequent seizures can lead to memory loss and other cognitive deficits,

The study published in the journal Nature Medicine may lead to future strategies to reduce cognitive deficits in Alzheimer's disease and other conditions associated with seizures, such as epilepsy.

"It's been hard to reconcile how infrequent seizures can lead to persistent changes in memory in patients with Alzheimer's disease," said corresponding author Jeannie Chin, Assistant Professor at Baylor College of Medicine in Houston, Texas, US.

"To solve this puzzle, we worked with a mouse model of Alzheimer's disease focusing on the genetic changes that seizures might trigger in the memory centre of the brain, the hippocampus, that could lead to loss of memory or other cognitive deficits," Chin said.

The researchers measured the levels of a number of proteins involved in memory and learning and found that levels of the protein deltaFosB strikingly increase in the hippocampus of Alzheimer's disease mice that had seizures.

In this study, the researchers found that after a seizure, the protein remains in the hippocampus for an unusually long time.

"Interestingly, because deltaFosB is a transcription factor, meaning that its job is to regulate the expression of other proteins, these findings led us to predict that the increased deltaFosB levels might be responsible for suppressing the production of proteins that are necessary for learning and memory," Chin said.

"In fact, we found that when the levels of deltaFosB increase, those of other proteins, such as calbindin, decrease," Chin said.

When researchers experimentally increased deltaFosB levels in normal mice, calbindin expression was suppressed and the animals' memory deteriorated, demonstrating that deltaFosB and calbindin are key regulators of memory.