Stay hungry to stay bright (one for Mr. Goddard)

John H. john at
Wed Jul 16 13:35:53 EST 2003

Starvation stimulates the brain
24 June 2003 17:00 GMT
The amount you eat and the time between meals affects the growth and
survival of neurons in your brain, says a US neuroscientist, who predicts
that couch potatoes will have low levels of a key neurotrophic factor.
Reducing food intake or spacing out meals - two different ways of undergoing
dietary restriction (DR) - has a huge effect on the production of
brain-derived neurotrophic factor (BDNF), says Mark Mattson, chief of
cellular and molecular neurosciences section at the US National Institute on
Aging in Maryland.

DR increases levels of BDNF by a factor of seven- to eightfold in several
parts of the brain, says Mattson, which promotes the survival of neurons and
makes them more resistant to different kinds of insult. "It also can promote
synaptic plasticity and enhance learning and memory, and it seems to promote
neurogenesis," he said.

Although most of this work has been carried out on animals, Mattson has just
received approval for a pilot study in humans, which should start in earnest
in about six months. His preliminary experimental design involves 20
volunteers, randomly assigned to one of two treatment groups.

The control group will eat three meals a day from a prescribed menu. The
experimental group will follow exactly the same menu, says Mattson, but will
be asked to eat all their food for a given day within a four-hour time
window. The results are eagerly awaited.

"In rats and mice on this kind of dietary restriction, their blood pressure
is down, resting heart rate is down, and then when you stress the animals,
they adapt better in terms of recovery of blood pressure and heart rate than
do animals on the normal diet," he said.

Mattson predicts that measurements of cardiovascular function, insulin
levels, and glucose tolerance will reveal that humans respond in the same

Because of the benefits to the brain that DR brings, he hopes that it could
even be useful for treating age-related degenerative disorders, such as
Alzheimer's and Parkinson's diseases.

In transgenic mouse models of these diseases, synaptic plasticity is altered
and learning is impaired, says Mattson. DR and subsequent elevation of BDNF
in the brain slows down the neurodegenerative process, he says.

However, because DR is not something that people are going to adopt readily,
Mattson has had to think of ways of simulating DR in a socially acceptable
manner. He is currently using gene therapy to express leptin in the
hypothalamus of mice, which has the effect of suppressing appetite.

"The gene therapy in mice is in essence mimicking the effects of a dietary
restriction because it reduces food intake," he said. And, neurons in the
brains of these mice are more resistant to MPTP - a potent neurotoxin that
selectively damages dopamine-producing cells and is used as a model for
Parkinson's disease.

Raising levels of BDNF in the brain holds promise for treating
neurodegenerative disease and neural injuries, says Bai Lu of the Section on
Neural Development and Plasticity at the National Institute of Child Health
and Human Development in Bethesda.

However, he says, because it's a protein, BDNF cannot cross the blood-brain
barrier so is difficult to introduce into the brain directly. Furthermore,
BDNF has many functions, so widespread elevation of this neurotrophic factor
could have unwanted side effects, Lu adds. This, he says, is why research
has focused on raising BDNF using indirect methods, such as DR.

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