Gene expression differences between neurons that show recovery-associated growth after stroke and neurons that don’t show such growth are reported in a study published online this week in Nature Neuroscience. These findings have the potential to identify novel therapeutic targets for the treatment of stroke in humans.
Recovery from stroke had been associated with the brain’s ability to reorganize by having spared regions assume functions carried out by the compromised tissue. This reorganization is thought to be sub-served, in part, by axonal growth or “sprouting” of spared neurons, which allows them to make new connections in the recovering brain. However, only a subset of spared neurons show sprouting and what makes these neurons “special” is unknown.
Thomas Carmichael and colleagues developed a technique that allowed them to selectively label and then isolate sprouting and non-sprouting neurons from the same rats after stroke. They then compared gene expression profiles of these two neuronal groups to identify differences. Because the majority of human stroke victims are older adults, they also compared gene expression differences between young and aged rats. Because stroke is an age-related disease, they also compared gene expression differences between young and aged rats and found a number of significant differences.
As proof of concept, the authors selected a set of the genes which were highly activated in sprouting neurons from aged rats and studied these further. They report that an epigenetic regulatory protein and a growth factor acted to promote sprouting, whereas up-regulated inhibitory myelin receptors acted to limit sprouting.