We have all encountered people, perhaps our grandparents, who now have trouble remembering things that they could instantly recall when they were younger. What happened to those missing memories? Why are they so hard for an older person to recall? Those memories used to be present in the brain and easily accessible. What has changed?
The prevailing wisdom is that if people live long enough, they will lose not just their physical strength, mobility, and robust, healthy body, but also their ability to recall facts and events that were easily recalled in their youth. What has changed? Have those memories disappeared completely? Or are they still there, somewhere in the brain, but inaccessible due to a breaking down of the recall mechanism?
Perhaps the latter.
Recent research shows that at least some of the decline is due to the gradual decline of a chemical in the brain.
In a recent paper in the 16 July 2021 issue of Molecular Psychiatry, a paper titled “Chondroitin 6-sulphate is required for neuroplasticity and memory in aging” describes experiments performed on lab mice that shed light on a mechanism by which memories fade, and points to how they could be restored.
Chondroitin 6-sulphate (C6S) is a chemical found in mammalian brains, such as those of mice and humans. A similar chemical, chondroitin 4-sulphate, affects some of the same brain components as C6S, but in the opposite direction. Whereas C6S promotes axon growth and plasticity, C4S inhibits them. The composition of chondroitin sulphate changes with age. In the lab mice, at birth, 18% of the chondroitin sulphates present in the brain were in the C6S form. At the end of development, this declines to 4%, and in aged mice it is less than one percent. This decrease leads to an increase in the ratio of C4S to C6S (C4S/C6S). The result is that the inhibitory nature of C4S dominates in aged brains.
To test the hypothesis that, the CS imbalance affected memory, the researchers performed three tests that were within the capability of both young and old mice. They were:
- Spontaneous Object Recognition (memory of novel objects)
- Spontaneous alternation (avoiding retrying an option that had already been tried)
- Marble Burying
These are all tests that are not confounded by the weaker strength and endurance of the older mice, which would bias the results of, for example, the Morris water maze test or the Barnes maze test. If an aged mouse fails a test because is too weak to continue swimming through a maze, that does not tell us whether it remembered the correct route.
I’m most interested in the marble burying task. It seems that if you provide a young mouse with a supply of glass marbles in a suitable environment with a dirt floor, the mouse will instinctively bury the marbles. You can gauge the mouse’s cognitive level by the number of marbles that it buries. More marbles buried equates to better memory of what the mouse is doing.
Old mice (age 20 months) did a much poorer job on these tasks than did the young mice (age 6 months). The researchers then restored the depleted C6S levels in 19 month old animals, using a virus to inoculate the mice with the C6S. Five weeks later the mice were tested for spontaneous object recognition, spontaneous alternation, and marble burying. Their performance improved to almost that of young mice on spontaneous object recognition, but were not improved in the spontaneous alternation or marble burying tests.
Transgenic mice that overexpressed a factor called chst3 showed no memory deficit in the spontaneous object recognition task. These mice also performed like young mice in the marble burying task, but were still impaired in the spontaneous alternation task.
This research is significant. If the ability of aged mice to remember as well as young mice, due to the injection of C6S into the brain, perhaps there is hope for aged humans too. In the mice, the ability to remember was lost in the old mice, but it was not lost forever. It could be recovered. Clearly, a lot more research must be done, but there is hope that someday this knowledge will lead to a similar treatment for humans. Perhaps we will not lose our marbles after all. All we need to do is remember where we buried them.
BIO:
Allen G. Taylor is a 40-year veteran of the computer industry and the author of over 40 books, including Develop Microsoft HoloLens Apps Now, Get Fit with Apple Watch, Cruise for Free, SQL For Dummies, 9th Edition, Crystal Reports 2008 For Dummies, Database Development For Dummies, Access Power Programming with VBA, and SQL All-In-One For Dummies, Third Edition. He lectures internationally on astronomy, databases, innovation, and entrepreneurship. He also teaches database development and Crystal Reports through a leading online education provider. For the latest news on Allen’s activities, check out his blog at wwwallengtaylor.com or contact him at allen.taylor@ieee.org.