Lethal retrograde axoplasmic transport of doxorubicin (adriamycin) to motor neurons. A toxic motor neuronopathy.
Doxorubicin (Adriamycin) is an autofluorescent anthracycline antibiotic that acts as a DNA intercalator. Following intraneural microinjection of 3 micrograms of doxorubicin into rat tibial nerve, fluorescence microscopy indicated that it is transported retrogradely to anterior horn cell bodies. Subsequently, these motor neurons underwent a progressive subacute degeneration that occurred over a period of 35-39 days. Combined electrophysiological and neuropathological methods indicated that dorsal root ganglion cells were relatively unaffected by this dose of toxin. The selective motor neuron degeneration produced by this agent raises the possibility that abnormalities of nucleic acid metabolism may be involved in the aetiology of motor neuron diseases.
England
J D
JD
Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia 19104.
Asbury
A K
AK
Rhee
E K
EK
Sumner
A J
AJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism; D001370:Axonal Transport; D004317:Doxorubicin / Q000378:metabolism / Q000633:toxicity*; D005727:Ganglia, Spinal / Q000187:drug effects; D008297:Male; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D009132:Muscles / Q000503:physiopathology; D009468:Neuromuscular Diseases / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012583:Schwann Cells / Q000187:drug effects
D004317:Doxorubicin