An age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke.
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.
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, California, USA.
Songlin
S
Li
Justine J
JJ
Overman
Diana
D
Katsman
Serguei V
SV
Kozlov
Christopher J
CJ
Donnelly
Jeffery L
JL
Twiss
Roman J
RJ
Giger
Giovanni
G
Coppola
Daniel H
DH
Geschwind
S Thomas
ST
Carmichael
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology; D020521:Stroke / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics