Expression of growth factor receptors in injured nervous tissue. I. Axotomy leads to a shift in the cellular distribution of specific beta-nerve growth factor binding in the injured and regenerating PNS.
We have studied beta-nerve growth factor (beta-NGF) receptor expression in the injured and regenerating chick PNS using [125I]-iodinated beta-NGF as a radioactive probe to map and quantitate autoradiographically the in situ distribution of specific [125I] beta-NGF binding. Two different mechanisms are involved in the reappearance of specific [125I] beta-NGF binding on the normally unlabelled adult peripheral nerves. The anterograde and retrograde axonal transport of beta-NGF binding sites leads to a rapid but transient accumulation of [125I] beta-NGF binding on both sides of crushed or transected sciatic and brachial nerves. There is a dramatic decrease in the axonal transport of beta-NGF binding sites, starting 1 day after nerve injury (1 DPO) and reaching basal levels of 10-20% of the control values at 3 to 10 DPO. Gradual but complete recovery of this axonal transport was noted in the sciatic neurites allowed to regain contact with their peripheral targets. A very different regulation pattern was observed for the local reappearance of specific [125I] beta-NGF binding on the endoneurial Schwann cells throughout the distal part of the axotomized nerve. It was first observed at 4 DPO, becoming maximal at 6 DPO. Reinnervation of the nerve after crush led to a rapid decrease of this specific [125I] beta-NGF binding, which followed a proximo-distal temporal gradient. These results show that axotomy leads to a drastic decrease in the axonal expression of [125I] beta-NGF binding, while causing its appearance on the Schwann cells of the denervated endoneurium. They suggest that these endoneurial cells may become the primary target for beta-NGF following axotomy and during regeneration.
Raivich
G
G
Department of Neuromorphology, Max-Planck Institute for Psychiatry, Martinsried, Federal Republic of Germany.
Kreutzberg
G W
GW
D000818:Animals; D001345:Autoradiography; D002645:Chickens; D007457:Iodine Radioisotopes; D007700:Kinetics; D009414:Nerve Growth Factors / Q000378:metabolism*; D009416:Nerve Regeneration; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries / Q000502:physiology*
D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor