Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 11, Pages 4664-4669Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0603243104
Keywords
anaplastic lymphoma kinase; neurotrophism; Schwann cell; nerve regeneration; denervation
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Regeneration in the peripheral nervous system is poor after chronic denervation. Denervated Schwann cells act as a transient target by secreting growth factors to promote regeneration of axons but lose this ability with chronic denervation. We discovered that the mRNA for pleiotrophin (PTN) was highly up-regulated in acutely denervated distal sciatic nerves, but high levels of PTN mRNA were not maintained in chronically denervated nerves. PTN protected spinal motor neurons against chronic excitotoxic injury and caused increased outgrowth of motor axons out of the spinal cord ex-plants and formation of miniventral rootlets. In neonatal mice, PTN protected the facial motor neurons against cell death induced by deprivation from target-derived growth factors. Similarly, PTN significantly enhanced regeneration of myelinated axons across a graft in the transected sciatic nerve of adult rats. Our findings suggest a neurotrophic role for PTN that may lead to previously unrecognized treatment options for motor neuron disease and motor axonal regeneration.
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