Restricting diet may reverse early-stage Parkinson's disease

A study suggests that early-stage Parkinson's disease patients who lower their
calorie intake may boost levels of an essential brain chemical lost from the
neurodegenerative disorder.

 The study by Charles Meshul, at the Oregon Health & Science University
( OHSU ) School of Medicine and the Portland Veterans Affairs Medical Center
VAMC's Neurocytology Lab, has shown that dietary restriction reverses a
Parkinson's-induced drop in glutamate, a brain neurotransmitter important for
motor control, function and learning, in a mouse model for the disease's
early stages.

 The results, presented at the Society for Neuroscience's 35th Annual Meeting,
are the first to show that a restricted diet can disable neurochemical
changes in the brain occurring in early-stage Parkinson's even after those
changes are observed.

 " In the early stages of the disease, we see certain markers in the brain
that are changing that may be indicative that dietary restriction is
helpful," Meshul said.

 Parkinson's disease is a progressive, degenerative disorder affecting a
region of the brain called the substantia nigra where movement is controlled.
 Symptoms such as tremor or shaking, muscular stiffness or rigidity, slowness
of movement and difficulty with balance appear when about 80 percent of cells
in the body that produce the neurochemical dopamine die or become impaired.

 Incidence increases with age, and the disease is uncommon in people younger
than 40.
 According to the OHSU Parkinson Center of Oregon, the disease affects both
men and women across all ethnic lines and occurs in about two of every 100
people older than 55.
 About 1.5 million Americans suffer from the disease.

 Meshul's lab compared two groups of mice with 60 percent to 75 percent loss
of dopamine in the brain, representing early-stage Parkinson's: one had
access to food every day while the other had access every other day, and both
were fed over a 21-day period. The mice that ate less often lost 10 percent
to 15 percent of their body weight compared to their counterparts.

 " Dietary restriction appears to be normalizing the levels of glutamate,"
Meshul said. " The fact that we're getting the levels of glutamate back to,
essentially, control levels may indicate there are certain synapse changes
going on in the brain to counteract the effects of Parkinson's. In fact, what
this may indicate is a reversal of locomotor deficits associated with the
disease."

 In addition to the rise in glutamate, Meshul's group, using a
dopamine-synthesizing enzyme called tyrosine hydroxylase as a marker for
dopamine nerve terminals, found that dietary restriction caused a drop in the
number of dopamine terminals in the mouse model for early-stage Parkinson's.

 " As it turns out, dietary restriction, in and of itself, had an effect. It
actually caused a small but significant decrease in the numbers of these
dopamine terminals. So in other words, dietary restriction really is doing
something to the brain," Meshul said. " It could very well be that what
dietary restriction is doing is trying to protect the system somehow. And one
of the reasons dietary restriction is protective may be that it's reducing
the activity of particular synapses. That's actually what the data
indicates."

 Matching the upturn in glutamate levels with positive behavioral changes is
difficult at this point in the research, Meshul said. " One of the
unfortunate problems with this model is it's tough to do any behavioral
measures. We see a reversal of the effect of glutamate in the brain due to
the dietary restriction, but what does that actually mean in terms of the
behavior of the animal ? Unfortunately, we don't know. We didn't measure
that."

 But a similar primate study at the University of Southern California that
Meshul is associated with is testing the hypothesis that glutamate does have
an effect on behavior. " It turns out that, in time, these animals recover
behaviorally from all of the motor deficits that are associated with
( early-stage Parkinson's )," he said. " Our hypothesis is there may be
changes in glutamate that account for these behavioral changes."

 Dietary restriction's beneficial effect on neurological function has been
studied in primates by scientists at the National Institutes of Health for 30
years, Meshul said. Researchers found that animals whose calorie intake was
lowered by 20 percent aged better, suffered from fewer immunological
disorders, displayed healthier hair and skin tone, and "looked significantly
better than a counterpart that hasn't had a restricted diet."

 "They live longer," Meshul said. "It's been known for many, many years that
dietary restriction is good."

 Scientists already have shown dietary restriction initiated before the onset
of early Parkinson's can protect against neurochemical changes in the brain
caused by the disease. In 1999, researchers found that mice on restricted
diets for three months prior to an early Parkinson's diagnosis lost fewer
dopamine-synthesizing neurons.

 "There's not as much loss of dopamine if you restrict their diets ahead of
time," Meshul noted.

 Meshul's lab is finding that dietary restriction isn't the only way to boost
neurological function in Parkinson's disease. Early results of another study
the group is conducting have shown that rats with 90 percent loss of dopamine
in the brain - or full-blown Parkinson's disease - under a four-week exercise
regimen can run twice as long as parkinsonian rats that didn't exercise.

 "We're trying to make the correlation that exercise definitely helps in terms
of the parkinsonian animal and, in fact, in human studies it's been shown
that any sort of exercise helps patients," Meshul said.

 Source: Oregon Health & Science University, 2005


 XagenaMedicine2005

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