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Gene Modifying Study Shedding New Light on Alzheimer's and Other Neuro-Degenerative Diseases
In a University of Rochester laboratory study that could help in deciphering Alzheimer's disease, scientists are finding that genetically altered mice learned and remembered better when subjected to tricky maze exercises. The mice were boosted with a neuron-nourishing protein called nerve growth factor; this research marks the first time a specific molecule has been pinpointed to assist the brain in rewiring itself to tackle new challenges.
"The interaction between the learning experience and this gene caused a rather striking reorganization" in a brain pathway considered vital to spatial learning and memory, explained lead researcher Dr. Howard Federoff, director of the university's Center For Aging and Developmental Biology. "The genetically engineered mice not only learned better than the non-engineered ones but their memory improved."
Alzheimer's is a progressive neurological disease that now affects more than 4 million Americans. Victims, most of them elderly, suffer gradual and irreversible memory loss, disorientation and personality changes.
Federoff developed a gene-transfer method used in the study in which extra copies of a gene that generates nerve growth factor are delivered to cells in the hippocampus, a part of the brain thought to have a central role in memory processes as it serves as a way station for funneling and retrieving information. After three months, when the mice reached adulthood, a virus was used to turn on the gene. The nerve growth factor allows cells to grow and maintain fibers that link neurons in the braineven those in distant locations.
The mice who'd received the virus and an equal number who did not have the gene triggered--about 80 mice in all--were divided into 3 groups. Over a period of 2 weeks, one group stayed in their cages, one group ran through the same simple maze day after day, and the third group was continually challenged to navigate new mazes.
The study (published in November in Proceedings of the National Academy of Sciences) determined that the genetically modified mice were the quickest and most adept learners and that specific neurons in the basal forebrain at the base of their skulls were on average 60% bigger than those in the mice that were not given a workout. The maze exercises appeared to be a key stimulant "in enhancing the nerve growth factor's effect on the brain circuitry, in driving reorganization," noted Federoff. And he added, "During 9 months of researchlong enough for the mice to grow well into middle ageno adverse consequences of the genetic modification were uncovered."
The researchers' aim was to manipulate a critical pathway in learning that runs from the basal forebrain area to the hippocampus. Federoff pointed out that "in virtually every patient who has Alzheimer's disease, cells that manufacture the neurotransmitter acetylcholine are diseased and their function is profoundly decreased. The most modern drugs to treat Alzheimer's disease are intended to increase the amount of acetylcholine." His research team continues to carry out studies to try to develop a strategy in which "we can envision a potential for ameliorating symptoms of Alzheimer's disease." Federoff said he hopes to conduct clinical trials within a few years.
Dr. Bill Thies, vice president for medical and scientific affairs at the Chicago-based Alzheimers Association, said the University of Rochester study holds the promise of developing gene therapies for a variety of neuro-degenerative diseases: "If something like this works for Alzheimers disease, by putting your gene modification in another place you might get it to work for Parkinson's disease and other diseases where you have a death of nerve cells for a variety of reasons."
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