CNTF and GDNF, but not NT-4, support corticospinal motor neuron growth via direct mechanisms.
Axotomy and neurodegenerative diseases cause corticospinal motor neuron (CSMN) degeneration. We previously showed that CNTF, NT-4 and GDNF can support CSMN survival in enriched preparations. Here we developed a fluorescence-activated cell sorting method to highly purify CSMN (97+/-4.6%). We tested the neurotrophic activities of CNTF, NT-4 and GDNF on enriched and purified CSMN preparations. Similar to their effects on enriched CSMN preparations, CNTF and GDNF sustained the survival of purified CSMN for at least 5 days with ED50 values of 1.28+/-0.46 nM and 0.59+/-0.39 nM, respectively. In contrast, NT-4 supported survival of enriched but not of purified CSMN, indicating that CNTF and GDNF sustain motor neuron survival by direct action of CSMN, while NT-4 requires accessory cells present in enriched CSMN preparations.
Junger
H
H
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA.
Junger
W G
WG
D000818:Animals; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D005434:Flow Cytometry; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D020934:Ciliary Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C073922:neurotrophin 4