Health of normal synapses seen to depend on neurotrophin signaling

In a new study, researchers at the University of Pennsylvania Medical Center have shown that the long-term health of synapses -- the connections between brain cells -- depends on ongoing signaling by a family of compounds called neurotrophins. Although neurotrophins are known to be critical during development, the current findings are among the first to show the importance of neurotrophin signaling at adult synapses. A report of the study appears in the November 24 issue of Neuron.

The results have implications for understanding how synapses are maintained in development and in adulthood, and suggest that neurotrophins may protect synapses from atrophy in aging and patients with certain neuromuscular diseases or injuries. In their experiments, the scientists used a novel technique borrowed from gene therapy to block normal neurotrophin activity in a type of synapse called the neuromuscular junction. They demonstrated that the synapses of developing and adult mice fall apart in the absence of particular neurotrophins.

The results are evocative of the synaptic changes seen in aging, muscular weakness and other diseases, suggesting that artificially augmenting neurotrophin signaling might someday be used to protect against certain kinds of synaptic failure.

"In aging animals and in aging humans, the synapse we studied -- the neuromuscular junction -- falls apart over time in much the same way it did in our neurotrophin experiments," says Rita J. Balice-Gordon, Ph.D., an assistant professor of neuroscience and senior author on the study. "Below a certain threshold, neurotrophin-deprived synapses begin to lose function. This nerve-signaling failure is one reason for the decrease in muscle strength in old age. So, one question we'll be looking at in the future is whether neurotrophin treatment of aging synapses might slow this process down." "What we've done argues that, in any disease or injury where the neuromuscular junction or other synapse is

Contact: Sue Montgomery
University of Pennsylvania School of Medicine

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