Neuronal injury increases retrograde axonal transport of the neurotrophins to spinal sensory neurons and motor neurons via multiple receptor mechanisms.
We investigated the retrograde axonal transport of 125I-labeled neurotrophins (NGF, BDNF, NT-3, and NT-4) from the sciatic nerve to dorsal root ganglion (DRG) sensory neurons and spinal motor neurons in normal rats or after neuronal injury. DRG neurons showed increased transport of all neurotrophins following crush injury to the sciatic nerve. This was maximal 1 day after sciatic nerve crush and returned to control levels after 7 days. 125I-BDNF transport from sciatic nerve was elevated with injection either proximal to the lesion or directly into the crush site and after transection of the dorsal roots. All neurotrophin transport was receptor-mediated and consistent with neurotrophin binding to the low-affinity neurotrophin receptor (LNR) or Trk receptors. However, transport of 125I-labeled wheat germ agglutinin also increased 1 day after sciatic nerve crush, showing that increased uptake and transport is a generalized response to injury in DRG sensory neurons. Spinal cord motor neurons also showed increased neurotrophin transport following sciatic nerve injury, although this was maximal after 3 days. The transport of 125I-NGF depended on the expression of LNR by injured motor neurons, as demonstrated by competition experiments with unlabeled neurotrophins. The absence of TrkA in normal motor neurons or after axotomy was confirmed by immunostaining and in situ hybridization. Thus, increased transport of neurotrophic factors after neuronal injury is due to multiple receptor-mediated mechanisms including general increases in axonal transport capacity.
Curtis
R
R
Regeneron Pharmaceuticals Inc., Tarrytown, New York, 10591-6707, USA. curtis@mpi.com
Tonra
J R
JR
Stark
J L
JL
Adryan
K M
KM
Park
J S
JS
Cliffer
K D
KD
Lindsay
R M
RM
DiStefano
P S
PS
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D019771:Axotomy; D001693:Biological Transport, Active / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology*; D019051:Rhizotomy; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface