Midkine (MK), a heparin-binding growth factor, is produced in the developing and damaged nervous system. However, the role of MK in peripheral nerve injury has not been clarified. Here, we investigated MK expression in lumbar spinal motor neurons after rat sciatic nerve injury by immunohistochemical, in situ hybridization, and Western blot analyses. The rat sciatic nerve showed complete degeneration after local freezing. Numerous regenerated myelinated and thin nerve fibers were observed 3 weeks after injury. Intense MK immunoreactivity was detected in the ipsilateral spinal motor neurons of the anterior horn of the lumbar spinal cord after 1 day and in ipsilateral and contralateral spinal motor neurons from 4 days to 1 week after injury. It decreased after 2 weeks and again transiently increased in spinal motor neurons after 3 weeks. MK was found in the motor neurons and axon of the sciatic nerve. However, it was not detected in normal neurons and axon. In situ hybridization showed the expression of MK mRNA in lumbar spinal motor neurons of the anterior horn, but it was not present in Schwann cells or non-neuronal cells. Low-density lipoprotein receptor-related protein (LRP) immunoreactivity, a cell membrane receptor of MK, was observed in anterior horn motor neurons, but receptor-type protein tyrosine phosphatase ζ (PTPζ) immunoreactivity as a signaling receptor complex of MK was not observed. LRP and PTPζ immunoreactivities were observed in Schwann cells of the injured and uninjured sciatic nerve. Our findings suggest that MK is synthesized, released, and taken up in anterior horn motor neurons in an autocrine fashion with LRP. MK may have a role in degeneration and regeneration after peripheral nerve injury.
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