The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons.
The pattern of retrograde axonal transport of the target-derived neurotrophic molecule, nerve growth factor (NGF), correlates with its trophic actions in adult neurons. We have determined that the NGF-related neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are also retrogradely transported by distinct populations of peripheral and central nervous system neurons in the adult. All three 125I-labeled neurotrophins are retrogradely transported to sites previously shown to contain neurotrophin-responsive neurons as assessed in vitro, such as dorsal root ganglion and basal forebrain neurons. The patterns of transport also indicate the existence of neuronal populations that selectively transport NT-3 and/or BDNF, but not NGF, such as spinal cord motor neurons, neurons in the entorhinal cortex, thalamus, and neurons within the hippocampus itself. Our observations suggest that neurotrophins are transported by overlapping as well as distinct populations of neurons when injected into a given target field. Retrograde transport may thus be predictive of neuronal types selectively responsive to either BDNF or NT-3 in the adult, as first demonstrated for NGF.
DiStefano
P S
PS
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591-6707.
Friedman
B
B
Radziejewski
C
C
Alexander
C
C
Boland
P
P
Schick
C M
CM
Lindsay
R M
RM
Wiegand
S J
SJ
D000818:Animals; D001370:Axonal Transport; D019208:Brain-Derived Neurotrophic Factor; D016466:CHO Cells; D006224:Cricetinae; D005727:Ganglia, Spinal / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020933:Neurotrophin 3; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3