Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation.
The peripheral branch of primary sensory neurons regenerates after injury, but there is no regeneration when their central branch is severed by spinal cord injury. Here we show that microinjection of a membrane-permeable analog of cAMP in lumbar dorsal root ganglia markedly increases the regeneration of injured central sensory branches. The injured axons regrow into the spinal cord lesion, often traversing the injury site. This result mimics the effect of a conditioning peripheral nerve lesion. We also demonstrate that sensory neurons exposed to cAMP in vivo, when subsequently cultured in vitro, show enhanced growth of neurites and an ability to overcome inhibition by CNS myelin. Thus, stimulating cAMP signaling increases the intrinsic growth capacity of injured sensory axons. This approach may be useful in promoting regeneration after spinal cord injury.
Neumann
Simona
S
Department of Anatomy and W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, CA 94143, USA.
Bradke
Frank
F
Tessier-Lavigne
Marc
M
Basbaum
Allan I
AI
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*
D003994:Bucladesine; D000242:Cyclic AMP