Transganglionic Neuropeptide Y Response to Sciatic Nerve Injury in Young and Aged Rats

Abstract

Gracile neuroaxonal dystrophy (NAD) is a hallmark of the aging human and rodent sensory nervous systems which may represent an abnormal transganglionic response to peripheral axonal injury. To examine the structural plasticity of central dorsal root ganglia (DRG)-derived axons in the gracile nucleus, we evaluated the response of the lumbar DRG and their central projections to sciatic nerve injury in young and old rats. In uninjured rats neither the DRG nor its central projections contained histochemical immunoreactivity for neuropeptide Y (NPY). However, within 1 week of sciatic nerve crush or transection injury, NPY immunoreactivity appeared in the lumbar DRG and its central projections, reaching an apparent maximum in number and intensity of processes at 28 days. Neuropeptide Y immunoreactivity was more intense and sustained in response to transection compared to crush injury, results supported by NPY radioimmunoassay. Neuropeptide Y-immunoreactive processes in the gracile nuclei of axotomized young animals consisted of delicate axons or slightly enlarged profiles that may represent regenerative elements. Lumbar dorsal rhizotomy performed simultaneously with sciatic nerve transection prevented the transganglionic NPY response. Dystrophic axons in the gracile nucleus of non-lesioned aged animals were not NPY-immunoreactive; however, after sciatic nerve transection, NPY immunoreactivity developed in both delicate axons and markedly swollen dystrophic elements, a finding confirmed by ultrastructural immunolocalization. These results establish that despite the presence of NAD in DRG projections to aged gracile nuclei these elements remain capable of a plastic NPY response to peripheral nerve injury.