Restricting diet may reverse early-stage Parkinson's disease

[Guest guest]

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 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