Wednesday August 15 02:36 AM EDT
Brain Degeneration Reversed in Mice
By Nicolle Charbonneau
HealthScoutNews Reporter
TUESDAY, Aug. 14 (HealthScoutNews) --

Brain cells that were presumed to have died in elderly patients with Down syndrome or Alzheimer's disease may only have been cut off from a crucial protein, says new research.

And a direct infusion of the protein appears to restore the cells completely in mice, suggesting that similar neuro-degeneration in humans could be reversed, the study says.

Stanford University researchers looked at a group of cells in an area of the brain called the basal forebrain, which along with the hippocampus is crucial for learning and memory.

"We know that these are populations of cells that degenerate in both Alzheimer's disease and Down syndrome," says lead study author Jonathan Cooper, a senior lecturer in experimental neuropathology at King's College in London. The research appears in today's issue of the Proceedings of the National Academy of Sciences (news - web sites).

The cells, called basal forebrain cholinergic neurons, shrivel up or die as patients with these disorders age, contributing to their cognitive decline.

Cooper and his colleagues say they believe the degeneration of these neurons is related to a problem in the transport of nerve growth factor, a protein critical to brain development and function.

In mice with a condition comparable to Down syndrome in humans, Cooper found that something was interfering with the pathway that nerve growth factor follows to the basal forebrain.

"They're still making this protein," but says Cooper, "Somehow, there's some kind of roadblock that prevents it from getting back [to the basal forebrain]."

To bypass the roadblock, the researchers directly infused the spaces around the basal forebrain with nerve growth factor.

"We found two very surprising and exciting things. The remaining cells that were there that looked shrunken were actually restored to their full size, and this was even in the old, 18-month-old animal," says Cooper.

"More excitingly still, it completely restored the number of these cells," suggesting that cells presumed dead may actually have been in a dormant state until the nerve growth factor returned, he says.

Cooper says the findings raise hopes of reversing neuro-degeneration in humans with Down syndrome and Alzheimer's, particularly if treatment could be started at an early stage of neuro-degeneration.

However, the researchers say they can't yet tell whether the nerve growth factor restores the cells' function and what causes the interference with the transport of nerve growth factor to the basal forebrain in the first place.

Dr. Howard Federoff, director of the University of Rochester's Center for Aging and Developmental Biology in Rochester, N.Y., says the findings are of considerable interest for research into Down syndrome and Alzheimer's disease.

"The fact that they can restore that signaling by the infusion of nerve growth factor suggests to me ... this may have some ultimate therapeutic value," says Federoff.

Although the researchers were able to reverse the neuro-degeneration in an older mouse, he says treating the problem as early as possible would be better. "The longer that you let that process go on, the neuron is going to be less capable of fully recovering," says Federoff.

Cooper says upcoming studies will look for the functional effects of the treatment in animals and determine any side effects.

More than 350,000 people in the United States have Down syndrome, while approximately 4 million Americans have Alzheimer's disease.