3-NITROPROPIONIC ACID (3-NPA)-INDUCED AXONAL DEGENERATION - A SILVER IMPREGNATION STUDY

Inhibition of energy metabolism can produce central and peripheral axo nopathy and increased sensitivity to excitotoxicity. A silver impregna tion technique was used to determine the localization of 3-nitropropio nic acid (3-NPA) induced neuronal or axonal degeneration. 3-NPA, an in hibitor of succinate dehydrogenase, was continuously given to rats for up to 7 days. Silver degeneration staining in the fibre pathways whic h course through the thalamus, the caudate-putamen, the internal capsu le, the external capsule and the medial forebrain bundle first appeare d after 5 days of 3-NPA intoxication. Intoxicated rats exhibited an at axic gait and significant weight loss. At 7 days the degeneration patt ern was similar, but there was increased staining present rostrally in fibre pathways dispersed throughout the caudate-putamen. Removal of 3 -NPA after 5-6 days resulted in an increased body weight by 4-5 days a nd the disappearance of the ataxic gait. Axonal degeneration continued for 8 and 9 days after toxin removal with additional degeneration pre sent in the caudate-putamen and the internal capsule. These data indic ate that, in addition to the excitotoxic neurodegeneration, continuous 3-NPA (6.8 mg/kg/day) administration produces axonal damage.