An age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke.

TitleAn age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke.
Publication TypeJournal Article
Year of Publication2010
AuthorsLi, S, Overman JJ, Katsman D, Kozlov SV, Donnelly CJ, Twiss JL, Giger RJ, Coppola G, Geschwind DH, Carmichael TS
JournalNature neuroscience
Volume13
Issue12
Pagination1496-504
Date Published2010 Dec
ISSN1546-1726
KeywordsAging, Animals, Axons, Cells, Cultured, Gene Expression Profiling, Male, Mice, Mice, Inbred C57BL, Rats, Rats, Inbred F344, Recovery of Function, Sensory Receptor Cells, Stroke, Up-Regulation
Abstract

Stroke is an age-related disease. Recovery after stroke is associated with axonal sprouting in cortex adjacent to the infarct. The molecular program that induces a mature cortical neuron to sprout a new connection after stroke is not known. We selectively isolated neurons that sprout a new connection in cortex after stroke and compared their whole-genome expression profile to that of adjacent, non-sprouting neurons. This 'sprouting transcriptome' identified a neuronal growth program that consists of growth factor, cell adhesion, axonal guidance and cytoskeletal modifying molecules that differed by age and time point. Gain and loss of function in three distinct functional classes showed new roles for these proteins in epigenetic regulation of axonal sprouting, growth factor-dependent survival of neurons and, in the aged mouse, paradoxical upregulation of myelin and ephrin receptors in sprouting neurons. This neuronal growth program may provide new therapeutic targets and suggest mechanisms for age-related differences in functional recovery.

DOI10.1111/j.1460-9568.2012.08054.x
Alternate JournalNat. Neurosci.