A new study by Penn State researchers has found that blocking a specific enzyme in older mice enhances their ability to update memories, bringing scientists closer to potential treatments for age-related cognitive decline.
Memory lapses are a common issue as people age, often resulting in difficulty recalling new information and updating old memories with new details. Despite its prevalence, the underlying mechanisms of this challenge have largely remained a mystery — until now. Researchers at Penn State have uncovered a significant breakthrough, identifying an enzyme that contributes to memory updating problems in older adults.
In a groundbreaking study published in Frontiers in Molecular Neuroscience, the team demonstrated that blocking histone deacetylase 3 (HDAC3) in older mice improved their ability to incorporate new information and update existing memories.
“We’re constantly building on things we already know and modifying existing memories,” Janine Kwapis, assistant professor of biology and senior author of the paper, said in a news release. “But no one has really looked to see if the mechanisms behind memory formation and memory updating are identical or if they are unique for memory updating. This is a step forward in figuring that out.”
Memory formation involves the brain consolidating information, a process where proteins at the synapse link neurons together, creating a network that fires simultaneously when a memory is recalled. The challenge increases with age, as the process of reconsolidation — where a memory is weakened and updated with new information — becomes less effective.
“When you’re presented with new information, you have to bring that existing memory out of storage and weaken it so it’s ready to take on new information,” added Kwapis.
The researchers sought to understand if enhancing gene expression during this update process could improve memory reconsolidation. They focused on HDAC3, an enzyme known to negatively affect memory formation and gene expression during consolidation. This study is the first to investigate HDAC3’s role in memory updating.
“If we block this enzymatic activity from happening, it may help maintain a more open chromatin state and improve gene expression,” said Chad Smies, a doctoral student in biology and first author of the paper, in the news release.
Using a methodology called the “objects in updated locations paradigm,” developed specifically to test memory updating, the team trained mice to learn locations of objects, moved one of the objects and then tested the mice’s memory. Older mice with blocked HDAC3 performed as well as their younger counterparts in recognizing new object locations.
“Mice like novelty so if they have good memory for the training session or the update session, they’ll explore the novel object location more,” Smies added.
The implications of this study are far-reaching. By identifying molecular mechanisms like HDAC3, the researchers hope to pave the way for therapeutic targets that can improve cognitive flexibility in aging populations, and potentially those with conditions such as Alzheimer’s disease and dementia.
“If these mechanisms improve memory in normal aging, they could potentially help with conditions like Alzheimer’s disease and dementia too,” added Kwapis.
This study marks a significant milestone in understanding and potentially mitigating age-related cognitive decline, giving hope to millions seeking ways to maintain their mental acuity well into old age.