Apr. 9, 1998 DURHAM, N.C. -- Pregnant rats fed extra doses of an essential nutrient called choline produced offspring whose brain circuits were "wired" to learn and remember far more efficiently than offspring without the supplement, according to a study at Duke University Medical Center.
Conversely, analysis of brain slices of the offspring of rats deprived of choline indicated a decrease in memory capability.
The researchers said it is the first time that a common food nutrient has been shown to cause permanent brain changes in regions responsible for learning and memory. The findings could have important implications -- especially for pregnant women and their children -- if choline proves to have the same memory-enhancing effect in humans, a theory for which considerable evidence already exists, the researchers said.
Choline is a naturally occurring amino acid found in egg yolks, milk, nuts, liver and other meats as well as in human breast milk. It is the essential building block for a memory-forming brain chemical called acetylcholine, and it plays a vital role in the formation of cell membranes throughout the body.
The Duke researchers found that brain circuits of choline-supplemented rats were built to accept and retain new information more efficiently than rats that received normal or substandard amounts of choline prenatally. And that memory enhancement endured until the rats were 4 months old -- the equivalent of early adulthood in humans.
Specifically, the research showed that choline enhanced a brain function called long-term potentiation (LTP), in which the act of receiving an electrical stimulus or "message" actually paves a pathway allowing future messages to reach the nerve cell more easily -- similar to the way that rain water creates a furrow through soil upon repeated downpours, enabling even a small trickle to find its way more easily.
If further research confirms the findings in humans, then choline could potentially be used to ensure normal memory function in the population at large through a modest change in diet, said Scott Swartzwelder, a neuropsychologist at Duke and the Durham VA Medical Center and lead author of the study. Results of his study, funded by the National Institute on Aging, will be published in the April issue of the journal of Neurophysiology.
"The ramifications of this research could be profound, because we've found that manipulating one single nutrient for a few days during gestation has a lifelong effect on brain function," Swartzwelder said. "In theory, we could develop ways to significantly reduce age-related memory deficits."
Swartzwelder said the amount of choline the pregnant rats received was well within normal limits -- about three times more than the control group received. The only time they received additional choline was during a five-day period -- days 12 through 17 -- of their 22-day gestation period. The control group received a normal dietary amount of choline, and a third group was virtually deprived of choline.
Not surprisingly, Swartzwelder said, the brains of choline-deprived rats were slower to engage the process of LTP and required a much larger stimulus to initiate LTP than the other rats.
While Swartzwelder's research is not the first to demonstrate choline's effects on memory, his is the first study reported to pinpoint the specific brain process that choline enhances.
In previous choline studies conducted at Duke, researchers showed that rats exposed to choline prenatally were better able to learn and remember the location of food in a maze, as well as to locate and swim to safety on a hidden platform in a water-filled maze. And, their memory abilities lasted well into old age. That research, conducted by Christina Williams and Warren Meck of Duke -- both co-authors of the current study -- was among the first to show that choline has a behavioral effect on memory in animals.
But until now, there has never been a physiologic explanation as to why these behavior changes occurred, said Williams, chair of the department of psychology at Duke. So, based on her behavioral studies, Swartzwelder set out to explain how choline alters memory function. By analyzing brain slices from the offspring of rats in each group, Swartzwelder showed that rats deprived of choline prenatally did not respond to even the largest electrical stimulus applied to their brain's hippocampus -- the region where LTP occurs. But the offspring of choline-supplemented animals responded very quickly and easily to the smallest electrical stimulus, indicating their hippocampus was primed to learn.
"What this suggests is an actual change in brain circuitry brought about by added choline during a critical window of prenatal development," Swartzwelder said. "The brains of choline-supplemented rats have a greater plasticity, or an ability to change and react to stimuli more readily than other rats."
Precisely why LTP occurs more readily in the choline-supplemented rats is unclear, Swartzwelder said. But there are several likely scenarios. One hypothesis is that extra choline permanently alters the developing brain circuits so they are built with either more acetylcholine receptors, or they have a greater capacity to produce acetylcholine.
A second possibility is that something inside individual nerve cells is altered to respond to acetylcholine more readily, regardless of the amount of acetylcholine present. In yet a third scenario, researchers hypothesize that there is no significant change in acetylcholine brain circuitry. Rather, choline affects a completely different neurotransmitter system, such as glutamate.
Swartzwelder said the next step is to examine the biochemistry within the various brain circuits to see which neurotransmitter systems are likely to play a role in enhancing LTP.
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