Scientists at Buffalo University (New York, USA) have discovered a new approach that could restore memory in patients with Alzheimer's disease, according to a pre-clinical study published today in the Mozak Journal.
"In this report, we have not only identified epigenetic factors that contribute to the loss of memory, but we have also found ways to temporarily reverse them in the animal model," said lead author Zhen Ian, a researcher at the university.
The team found that by focusing on genetic changes caused by non-DNA sequences, called epigenetic, it was possible to reverse memory damage in mice.
The study was conducted on models of mice with familial genetic mutations in the Alzheimer's gene, where more than one family member suffers from this disease and the brain tissue of dead human patients.
Epigenetic changes in Alzheimer's disease occur mainly when patients can not keep up-to-date information and show an accentuated cognitive decline.
The key reason for cognitive decline is the loss of glutamate receptors, which are critical to learning and short-term memory.
"We found that in Alzheimer's disease, many subunits of the frontal cortex receptor glutamate are regulated down, interrupting excitatory signals, which affects memory," said Ian.
The researchers found that the loss of glutamate receptors was the result of an epigenetic process known as repressive histone modification, which was elevated in Alzheimer's patients.
According to authors, this 'abnormal' modification of histone associated with Alzheimer is what suppresses gene expression, reducing glutamate receptors, which leads to loss of synaptic function and memory deficiency.
When this dysfunction was detected, injected compounds were designed to inhibit the enzyme that controls repressive histone modification three times in the diseased mice.
"When we gave this enzyme inhibitor to animals of Alzheimer's disease, we saw that rescue of cognitive function was confirmed by assessing the memory of memory, spatial memory and working memory," says the researcher.
"We were quite surprised to see such a drastic cognitive improvement," added Ian.
At the same time, the authors confirmed the recovery of expression and the function of glutamate receptors in the frontal cortex.
These improvements lasted for a week, so future studies will focus on the development of compounds that penetrate more effectively into the brain and are therefore more durable.