NEUROTOXICITY IN PRIMARY SENSORY NEURONS OF ADRIAMYCIN ADMINISTERED THROUGH RETROGRADE AXOPLASMIC TRANSPORT IN RATS

Abstract

Neurotoxic effects of adriamycin (ADM) were examined in rats. The drug was administered through retrograde axoplasmic transport from the transected sciatic nerve in very small amounts (0.05 mg of adriamycin). Using the autofluorescence specific to adriamycin as a histological tracer, alterations in primary sensory neurons in dorsal root ganglia (DRG) and in motor neurons in the spinal cord were observed chronologically by light and electron microscopy. In the DRG at the fifth and sixth lumbar levels, small neurons initially showed alterations in mitochondria, wavy nuclear membranes and enlarged cisternae of rough endoplasmic reticulum, and disappeared early in the experiments. Large neurons, which showed accumulation of neurofilaments, dense bodies and vacuoles in the perikarya in addition to nucleolar and nuclear chromatin alterations, degenerated slowly. In contrast, motor neurons in the anterior horn at the sixth lumbar level survived throughout the administration of adriamycin despite the presence of transient weak adriamycin autofluorescence and vacuoles in the cytoplasm. Thus, the susceptibility and vulnerability of motor neurons in spinal cord to adriamycin differed from that of primary sensory neurons; small neurons in the DRG were more susceptible than large sensory neurons. Administration through retrograde axoplasmic transport proved to be a useful technique for the evaluation of the neurotoxicity of adriamycin without the complications of systemic effects.