While glucose can have a bad reputation, in Paul Gold's lab it is being hailed as a possible hero that could restore memory retention for the aging and people with memory-deficient diseases, such as Alzheimer’s or Down syndrome.
“The effects in laboratory rodents have been really remarkable,” said Gold, a researcher in the College of Medicine. “With glucose treatments, old rats learn and remember as well as young rats do.”
Gold, a researcher in the College of Medicine, and his team made the discovery after studying the effects of stress on memory retention. Stress appears to release chemicals that enhance memory retention, which is why most people can remember vividly where they were when the World Trade Center collapsed, for example, and the first person they spoke with after hearing the news.
“Under stress, we remember things that aren’t even important to the main event,” said Paul Gold, a professor of psychology at the University of Illinois at Urbana-Champaign. “Arousal turns the brain on to remember in great detail much of what happens dur- ing that time.”
The Stress-Glucose Connection
If stress enhanced retention, Gold wondered if it could hold the key to unlocking the mysteries of memory. The researchers tested many hormones related to stress to see if any were linked to memory. They iden- tified several, but the one with the most robust ties was epinephrine, a hormone perhaps better known by the name adrenaline. However, as the researchers studied what was known about the actions of epineph- rine, they learned that epinephrine cannot cross the blood-brain barrier. Something outside the brain
must act as the intermediary.
This middleman agent was eventually identified as glucose. Stress releases epinephrine, which in turn increases blood glucose levels. Not only can glucose enter the brain, but the brain also has a mechanism for drawing it in.
Armed with this knowledge, Gold and his team shifted their focus and began administering glucose to labo- ratory animals. Researchers created a memory task – in this case, running through a maze – and measured the animals’ ability to remember with and without glu- cose.
The researchers found that as the animals learned, glucose levels decreased substantially in the brain area important for memory in this task. Administering glucose right to that brain area improved memory, indicating that the substance plays a key role in learn- ing and retention. Subjects of all ages showed marked improvement in their ability to remember. But the oldest animals showed the most astounding results. “Giving old animals glucose before the memory tests completely reversed the effects of aging,” Gold said. “The old rats had memory scores that were as good as those of young adult rats.”
In the context of aging, Gold says the results make sense. It is well known that old animals and people forget new information more quickly than their younger counterparts. They seem to use up brain glucose when learning new information and take a longer period to recover from depleted levels.
The larger deficiencies in brain glucose levels and the longer recovery time appear to reflect a disconnect between epinephrine release and increases in blood glucose levels in aged rats. While glucose enhances memory in both young and old rats, epinephrine only increases blood glucose – and therefore memory - in young rats, underscoring the importance of glucose in memory improvement.
Gold has repeated the results in a modified study among people. By administering lemonade with glu- cose before a memory test, healthy seniors performed as well on memory tests as college students. Alzheimer’s patients also showed dramatic improve- ment, as memory scores doubled with glucose, though still remaining far below those of other elderly subjects who did not have dementia.
The team’s next step will be to identify the mechanism by which glucose improves memory, which could lead to better pharmaceuticals for memory loss.
“All of these results are very encouraging,” Gold says. “It turns out old brains can learn new tricks. The goal is to identify treatments that can reverse the effects of aging on memory by going to the source, to the neurochemical actions of glucose that strengthen memory.”