Investigating the Role of GDF-10 in Brain Regeneration
Following a stroke, the survivors exhibit varying degrees of limited regeneration in the brain. Researchers are interested in finding reliable ways to enhance that process. Beyond the context of recovering from such injuries, it is important in the development of treatments for aging to be able to spur greater ongoing growth and regeneration in the aging brain:
Looking at brain tissue from mice, monkeys and humans, scientists have found that a molecule known as growth and differentiation factor 10 (GDF10) is a key player in repair mechanisms, such as axonal sprouting, that are activated following stroke. During axonal sprouting, healthy neurons send out new projections ("sprouts") that re-establish some of the connections lost or damaged during the stroke and form new ones, resulting in partial recovery. Before this study, it was unknown what triggered axonal sprouting. Previous studies suggested that GDF10 was involved in the early stages of axonal sprouting, but its exact role in the process was unclear. Examining animal models of stroke as well as human autopsy tissue, researchers found that GDF10 was activated very early after stroke. Then, using rodent and human neurons in a dish, the researchers tested the effect of GDF10 on the length of axons, the neuronal projections that carry messages between brain cells. They discovered that GDF10 stimulated axonal growth and increased the length of the axons.Researchers treated mouse models of stroke with GDF10 and had the animals perform various motor tasks to test recovery. The results suggested that increasing levels of GDF10 were associated with significantly faster recovery after stroke. When the researchers blocked GDF10, the animals did not perform as well on the motor tasks, suggesting the repair mechanisms were impaired - and that the natural levels of GDF10 in the brain represent a signal for recovery. It has been widely believed that mechanisms of brain repair are similar to those that occur during development. The team conducted comprehensive analyses to compare the effects of GDF10 on genes related to stroke repair with genes involved in development and learning and memory, processes that result in connections forming between neurons. Surprisingly, there was little similarity. The findings revealed that GDF10 affected entirely different genes following stroke than those involved in development or learning and memory. "We found that regeneration is a unique program in the brain that occurs after injury. It is not simply Development 2.0, using the same mechanisms that take place when the nervous system is forming."