Scientists closer to treating memory loss: what helped "rejuvenate" the brain
Kyiv • UNN
Researchers at Virginia Polytechnic Institute found that memory impairment is linked to specific molecular processes in the brain. Correcting these processes using gene editing technology restored memory in elderly rats.
Memory loss may not just be a sign of aging. Researchers at Virginia Polytechnic Institute have found that memory impairment is linked to specific molecular processes in the brain, and correcting them using gene-editing technology helped restore memory in older animals. This discovery could be a step towards new treatments for dementia and Alzheimer's disease, writes UNN with reference to Medical Xpress.
Details
Associate Professor Timothy Jerome of Virginia Polytechnic Institute, along with graduate students, conducted two studies using gene-editing technology to investigate age-related changes in the brain and ways to improve memory. The experiments were conducted on rats.
Memory loss affects more than a third of people over 70, and it is a major risk factor for developing Alzheimer's disease. This work shows that memory impairment is associated with specific molecular changes that can be specifically studied. If we can understand what drives this at the molecular level, we can begin to understand what goes wrong in dementia and ultimately use that knowledge to develop new treatment approaches.
In the first study, published in the journal Neuroscience, his team investigated a molecular "tagging" system that regulates protein behavior in the brain. Normally, this mechanism helps neurons exchange signals and form memories.
Scientists found that it deteriorates with age: its level increases in the hippocampus and decreases in the amygdala. By correcting these indicators using CRISPR-dCas13 technology, researchers were able to significantly improve memory in older rats.
Together, these results reveal important functions of K63 polyubiquitination in the process of brain aging. In both parts, correcting this single molecular process helped improve memory.
Reactivating a gene that supports memory
The second study, published in the journal Brain Research Bulletin under the direction of Jerome along with postdoctoral fellow Shannon Kincaid, focused on IGF2, a growth factor gene that supports memory formation. As the brain ages, IGF2 activity declines because the gene is chemically suppressed in the hippocampus.
IGF2 is one of a small number of genes in our DNA that is imprinted, meaning it is expressed from only one parental copy. When that single copy starts to diminish with age, you lose its beneficial properties.
Scientists found that gene silencing causes DNA methylation, a natural mechanism where chemical "tags" accumulate on the gene, blocking its activity.
Using CRISPR-dCas9 technology, researchers were able to remove these tags and reactivate the gene, leading to a significant improvement in memory in older rats.
Essentially, we turned the gene back on. When we did that, the older animals performed much better. Middle-aged animals that didn't yet have memory problems were unaffected, which tells us that timing matters. You have to intervene when something starts to go wrong.
Together, these two studies show that brain aging is likely influenced by numerous molecular systems.
We tend to look at one molecule at a time, but the reality is that many things are happening simultaneously. If we want to understand why memory declines with age or why we develop Alzheimer's disease, we need to look at the bigger picture.