Prenatal Choline Supplements Make Brain Cells Larger, Faster

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.

Source: Duke University