After injury, spinal neurons establish specialized bridges to connect with other injured neurons, according to new findings from researchers at the University of Pennsylvania Medical Center. Interestingly, the injured cells reach out only to each other in this process, excluding healthy neighboring cells from the network. The bridges - called gap junctions - are commonly found among neurons during development but are rarely seen in the adult mammalian nervous system. A report on the study appears in the January 15 issue of the Journal of Neuroscience (http://www.jneurosci.org/).
The results begin to suggest how connectivity between neurons in the spinal cord and between neurons and muscle might be re-established after peripheral nerve damage or spinal cord injury, areas for which current treatments are inadequate. The re-coupling of injured spinal neurons by gap junctions is similar to the coupling normally seen among neurons in developing animals. Finding ways to recapitulate this developmental phenomenon might therefore be an important part of future therapeutic efforts to rewire neurons and their targets after injury.
"Our study shows that neurons establish connection with other neurons after injury by creating bridges called gap junctions," says Rita J. Balice-Gordon, PhD, an assistant professor of neuroscience and senior author on the study. "The gap junctions are induced after nerve damage and may mediate electrical or biochemical communication between injured neurons."
"The presence of gap junctions could affect either neuronal activity or the exchange of second messengers and other small molecules," says Qiang Chang, BS, a graduate student in Balice-Gordon's laboratory and lead author on the study. "That, in turn, could encourage neuronal survival and promote rewiring after nerve injury."
The type of neurons investigated by the authors are the motor neurons in the spinal cord, the cells that control the movement of skeletal muscles. Scientists know that motor neurons change their function after nerve damage and can stop functioning or die after spinal cord injury or during the progression of diseases like ALS. Very little is known, however, about precisely how motor neurons change after injury or whether and how normal function might be restored.
Hoping to discover the nature of some of these changes and to gain insight into how spinal motor neurons cope with injury, the scientists experimentally severed the axons of these neurons in animal models. They then used glass needles connected to electronic recording equipment to listen to the injured neurons talking to each other. They also injected dyes into single injured motor neurons and looked for dye passing to other motor neurons. In this way, the researchers were able to assess whether the cells were directly connected by gap junction bridges. They found that the injured cells were connected by gap junction bridges and that they established the bridges only among themselves, failing to connect with nearby healthy cells.
The scientists also examined the proteins used to build these bridges, called connexins. They found that the amount and types of connexin proteins present in the neurons did not change after nerve injury. This suggests that gap junction bridges may be present among normal motor neurons but are perhaps inactive under normal circumstances.
Martin Pinter, PhD, with the Emory University School of Medicine, and Alberto Pereda, PhD, at the Medical College of Pennsylvania/Hahnemann School of Medicine at the time of the experimental work and currently at the Albert Einstein College of Medicine, are additional coauthors on the study.
Funding for the research was provided by the National Institutes of Health and the Spinal Cord Research Foundation of the Paralyzed Veterans of America.
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