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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.