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Prenatal Choline Supplements Make Brain Cells Larger, Faster

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Duke Health News 919-660-1306

DURHAM, N.C. -- The important nutrient choline
"super-charged" the brains of animals that received supplements
in utero, making their cells larger and faster at firing
electrical "signals" that release memory-forming chemicals,
according to a new study.

These marked brain changes could explain earlier behavioral
studies in which choline improved learning and memory in
animals, say the researchers from the departments of
pharmacology and psychiatry at Duke University Medical Center
and from the Durham VA Medical Center.

The implications for humans are profound, said the
researchers, because the collective data on choline suggests
that simply augmenting the diets of pregnant women with this
one nutrient could affect their children's lifelong learning
and memory. In theory, choline could boost cognitive function,
diminish age-related memory decline, and reduce the brain's
vulnerability toxic insults.

The Duke group is part of a national team of scientists who
are exploring the benefits of prenatal choline supplementation
on learning and memory. This ongoing research has been
instrumental in the Institute of
Medicine's decision
to elevate choline to the status of an
essential nutrient for humans -- particularly pregnant and
nursing women, the scientists said.

Results of their study, led by Qiang Li, M.D., of Duke and
the Durham VAMC, will be published in the April issue of
Journal of
Neurophysiology
.

"Previous studies at Duke have shown that
choline-supplemented animals are smarter and have a greater
learning capacity, but we hadn't known until now whether the
cells that make up memory-relevant brain circuits are changed
by choline" said Li. "Choline didn't just change the general
environment of the brain, it changed the fundamental building
blocks of brain circuits -- the cells themselves."

Choline is a naturally occurring nutrient found in egg
yolks, milk, nuts, fish, 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.

In the current study, the researchers explored the effects
of choline on neurons in the hippocampus, a brain region that
is critical for learning and memory. They fed pregnant rats
extra amounts of choline during a brief but critical window of
pregnancy, then studied how their hippocampal neurons differed
from those of control rats.

The researchers found that hippocampal neurons were larger,
and they possessed more tentacle-like "dendrites" that reach
out and receive signals from neighboring neurons.

"Having more dendrites means that a neuron has more surface
area to receive incoming signals," said Scott Swartzwelder,
Ph.D., senior author of the study and a neuropsychologist at
Duke and the Durham VA Medical Center. "This could make it
easier to push the neuron to the threshold for firing its
signal to another neuron." When a neuron fires a signal, it
releases brain chemicals called "neurotransmitters" that
trigger neighboring neurons to react. As neurons successively
fire, one to the next, they create a neural circuit that can
process new information, he said.

Not only were neurons structured with more dendrites, they
also "fired" electrical signals more rapidly and sustained
their firing for longer periods of time, the study showed. The
neurons also rebounded more easily from their resting phase in
between firing signals. These findings complement a previous
study by this group showing that neurons from supplemented
animals were less susceptible to insults from toxic drugs that
are known to kill neurons.

Collectively, these behaviors should heighten the neurons'
capacity to accept, transmit and integrate incoming
information, said Swartzwelder.

"We've seen before that the brains of choline-supplemented
rats have a greater plasticity -- or an ability to change and
react to stimuli more readily than normal rats -- and now we
are beginning to understand why," he said.

The researchers demonstrated these neuronal behaviors by
placing tiny electrodes within the neurons. Then, they prompted
neurons to fire signals by changing the electrical voltage
across the cells, (called depolarization). As neurons began to
fire, they measured their firing rates and the recovery
interval between each firing.

"Overall, we found that neurons in choline-exposed rats were
more excitable, more robust in their physiologic response,"
said Wilkie Wilson, Ph.D., a Duke pharmacologist and member of
the team at the Durham VAMC. "We've demonstrated a measurable
change in brain cells prompted by moderate amounts of choline
given during a narrow window of prenatal development."

Biochemical studies on the brain effects of choline at the
University of North Carolina at Chapel Hill and Boston
University have complemented the Duke findings, Wilson
said.

Steven Zeisel, M.D.,at the University of North Carolina at
Chapel Hill, has demonstrated that choline alters a gene called
CDKN-3 by adding a "methyl group" of atoms to the gene. The
methyl group switches off the gene and, in doing so, uninhibits
the cell division process in the memory centers of the
brain.

Tiffany Mellott and Jan Krzysztof Blusztajn, Ph.D., at
Boston University -- in collaboration with Christina Williams,
Ph.D., and Warren Meck, Ph.D., at Duke, -- recently found that
two hippocampal proteins known to participate in learning and
memory, called MAPK and CREB, are activated to a greater extent
in the animals prenatally supplemented with choline. These
studies provide biochemical correlates to the new data reported
by the Swartzwelder group.

Their collective research is funded by a program project
grant from the National Institute on Aging. Swartzwelder and
Wilson also received VA Senior Research Career Scientist
awards.

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