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Could This Protein Hold The Key To Preventing Memory Loss?

Researchers say that the discovery of a key protein, crucial to the retention of memory could play a significant role in the development of better drugs for memory loss.

There’s nothing more motivating to brain researchers than the issue of memory loss. Understanding the workings of the brain, the consolidation of memories and the reasons as to why and how we lose memories are all constantly being studied. 

Retaining our memories gives us all a sense of self and keeps us oriented to the world around us and our place in it. That’s why the understanding and prevention of chronic memory loss is a primary focus in the world of brain research. 

Not long ago, researchers from the University of Toronto Mississauga in Ontario, Canada — as well as researchers from the United States and the United Kingdom — investigated the role of a specific protein in the creation and retention of memory.

One of the lead researchers Iva Zovkic and her team performed their study using mice, looking specifically at a protein named H2A.Z. 

This particular type of protein called a histone, is able to bind to DNA, allowing it to keep its structure within cells.

The results of their study were published in the journal Cell Reports.1

H2A.Z And The Formation Of Memory

Zovkic and her research team used mice of varying ages, ranging from young to old in efforts to understand how the H2A.Z protein contributes to the formation and the suppression of memory.

Part of the experiment consisted of putting the mice in a new box, forcing them to get familiar with a strange environment.

Next, to look at how the protein functioned with regards to memory formation, the mice where then subjected to a negative stimulus within the box.

This was designed to give the mice a negative association with that new environment. The next time researchers placed the mice in the box they were much more cautious and resisted the urge to move around and explore their surroundings, which they normally do. 

30 minutes after the mice were exposed to the negative stimulus, Zovkic and her team evaluated the animals’ brains to determine if there were any changes to how H2A.Z bound to DNA.

Their findings showed that in younger mice, the fearful experience was associated with an “overwhelming” reduction of H2A.Z and DNA bonds. This was true and consistent in 3,048 places on the genes that proteins normally bind with. They also observed an increase of only 25 places where these proteins were bound.

When they looked at the older mice, their findings were the same. The older mice experienced a reduction in bonds at 2,901 places and only saw an increase of 9 places after the fear training.

The researchers went on to explain that this reduction in HsAZ bonding (fewer bonds between the protein and DNA) is associated with memory formation, this is what allows the mice to recall their negative experience.

"We have thousands of experiences each day, but we only remember things that are in some way important to us," Zovkic explained.

"This experiment," she went on to say, "used a very straightforward learning experience to illustrate that H2A.Z apparently serves to suppress memory, and the removal of this protein appears to [...] allow long-lasting memories to form."

Could This Be A New Therapeutic Target?

The animals age also appeared to be a factor in the levels of H2A.Z 

Older mice had higher levels of the protein in the hippocampi, a region of the brain associated with the formation of memory.

Based on their findings, Zovkic and the other researchers suggest that higher levels of H2A.Z are associated with the hindrance of memory and less retention. 

Therefore, if aging is associated with more H2A.Z bonds, that could explain what causes age-related memory loss. 

"Identifying H2A.Z as a unique protein that is involved with memory and increases with aging could be a big deal for creating genetic or pharmaceutical therapies for age-related cognitive decline and dementia. H2A.Z is a relatively specific therapeutic target." Says Zovkic.

The next experiment the researchers say will be to test the theory on extremely old mice. If the theory holds true and they’re able to confirm it with additional follow-up studies, researchers plan to move forward with human subjects. 

The research teams ultimate goal is to find new and better therapies to prevent and treat age related memory loss. 

"We're always trying to find molecular bases for memory,and discovering how genes related to memory are turned on and off is a step in a positive direction," Zovkic concludes.

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References:

1. Stefanelli, Gilda et al. "Learning And Age-Related Changes In Genome-Wide H2A.Z Binding In The Mouse Hippocampus." Cell Reports 22.5 (2018): 1124-1131.

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