Scientists have discovered the mechanism that explains how even relatively infrequent seizures can lead to memory loss, paving the way for future strategies to reduce cognitive deficits in diseases such as Alzheimer's and epilepsy.
Researchers from Baylor College of Medicine in the US measured the levels of a number of proteins involved in memory and learning.
They found that levels of the protein deltaFosB strikingly increase in the hippocampus of Alzheimer's disease mice that had seizures.
DeltaFosB already is well known for its association with other neurological conditions linked to persistent brain activity of specific brain regions, such as addiction, researchers said.
In the study, published in the journal Nature Medicine, researchers found that after a seizure, the deltaFosB 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," said Jeannie Chin, assistant professor at Baylor College of Medicine.
"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.
Further investigations supported the researchers' hypothesis. They showed that deltaFosB can bind to the gene calbindin suppressing the expression of the protein.
When they either prevented deltaFosB activity or experimentally increased calbindin expression in the mice, calbindin levels were restored and the mice improved their memory, researchers 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.
"Our findings have helped us answer the question of how even infrequent seizures can have such lasting detrimental effects on memory," Chin said.
Seizures can increase the levels of deltaFosB in the hippocampus, which results in a decrease in the levels of calbindin, a regulator of memory processes, researchers said.
DeltaFosB has a relatively long half-life, therefore even when seizures are infrequent, deltaFosB remains in the hippocampus for weeks acting like a brake, reducing the production of calbindin and other proteins, and disrupting the consequent brain activity involved in memory, they said.
The regulation of gene expression far outlasts the actual seizure event that triggered it, researchers added.
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