Mice bred with a mutation that leaves them free of the proteins Nogo A/B, which are believed to block re-growth of critical nerve fibers in the brain and spinal cord, sprout new axons following spinal cord injury, a Yale research team has found.
"In the mice with a mutation in the nogo gene that prevents Nogo A/B expression, the central nervous system (CNS) is largely normal but responds to injury in a unique fashion with robust axonal sprouting and long distance growth," said Stephen Strittmatter, professor of neurology and lead author of the study published in the April issue of the journal, Neuron. "The axons grew in the tail end of the spinal cord."
Nogo is a protein that has been identified as a component of the CNS myelin that prevents axonal regeneration. Different forms of nogo exist and are known as Nogo-A, Nogo-B, and Nogo-C.
In the adult mammalian CNS, injured axons exhibit little if any sprouting. The axons could be damaged in, for instance, a spinal cord injury, a head trauma, when the brain accelerates and decelerates, tearing axons and causing cognitive problems for a lengthy period of time, chronic progressive stages of multiple sclerosis, or in certain strokes.
The mice that Strittmatter's laboratory bred without Nogo/A and Nogo/B appeared normal. Following a spinal cord injury, new axons sprouted and recovery of locomotor function was improved.
Strittmatter cautioned that while the Nogo A/B deficiency is partially responsible for the effect of the mutation, other uncharacterized genetic factors may influence its expression. "Axon guidance for regenerating fibers is clearly not as precise as for developing fibers," he said. "Nonetheless, spinal injured Nogo A/B mice perform better in the open field than do control mice."
"Once we demonstrate that these two proteins are an important pathway in limiting growth, then we can pharmacologically improve functional recovery first in animals and then in humans," he said.
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