TY - JOUR
T1 - Axonal atrophy is a specific component of 2,5-hexanedione peripheral neuropathy
AU - Lehning, Ellen J.
AU - Dyer, Karen S.
AU - Jortner, Bernard S.
AU - Lopachin, Richard M.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1995/11
Y1 - 1995/11
N2 - To assess the relevance of previously identified axonal atrophy to hexanedione neuropathy, the present study quantitated fiber size in peripheral nerve of rats intoxicated with 2,5-hexanedione (HD) by either oral ingestion (0.4% in drinking water) or ip injection (0.4 g/kg/day). Prior to the appearance of neurobehavioral deficits, rats exposed to oral HD (77 days) exhibited axonal atrophy in proximal sciatic nerve and giant axonal swellings in distal tibial nerve. As oral-treated rats progressed to moderate (86 days) and severe (103 days) hindlimb weakness, both nerve regions contained a mixed population of atrophied and swollen axons. Rats injected with HD ip were sampled at behavioral endpoints that matched those of oral HD-treated rats. In sciatic and tibial nerves from rats treated ip, reductions in the axon area were similar to oral exposure. However, ip treatment did not produce giant axonal swellings in either nerve. Thus, although both routes of administration caused equivalent behavioral neurotoxicity, the expression of axonal swellings was route-dependent. This suggests that the production of swellings depends upon the HD exposure pattern. In contrast, axonal atrophy was prevalent in both nerve regions sampled and developed in parallel with behavioral deficits. In addition, atrophy was expressed regardless of the intoxication route which indicates that atrophy can occur independent of axonal swellings. Together, these attributes suggest that atrophy is a specific component of HD neurotoxicity.
AB - To assess the relevance of previously identified axonal atrophy to hexanedione neuropathy, the present study quantitated fiber size in peripheral nerve of rats intoxicated with 2,5-hexanedione (HD) by either oral ingestion (0.4% in drinking water) or ip injection (0.4 g/kg/day). Prior to the appearance of neurobehavioral deficits, rats exposed to oral HD (77 days) exhibited axonal atrophy in proximal sciatic nerve and giant axonal swellings in distal tibial nerve. As oral-treated rats progressed to moderate (86 days) and severe (103 days) hindlimb weakness, both nerve regions contained a mixed population of atrophied and swollen axons. Rats injected with HD ip were sampled at behavioral endpoints that matched those of oral HD-treated rats. In sciatic and tibial nerves from rats treated ip, reductions in the axon area were similar to oral exposure. However, ip treatment did not produce giant axonal swellings in either nerve. Thus, although both routes of administration caused equivalent behavioral neurotoxicity, the expression of axonal swellings was route-dependent. This suggests that the production of swellings depends upon the HD exposure pattern. In contrast, axonal atrophy was prevalent in both nerve regions sampled and developed in parallel with behavioral deficits. In addition, atrophy was expressed regardless of the intoxication route which indicates that atrophy can occur independent of axonal swellings. Together, these attributes suggest that atrophy is a specific component of HD neurotoxicity.
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U2 - 10.1006/taap.1995.1208
DO - 10.1006/taap.1995.1208
M3 - Article
C2 - 7482540
AN - SCOPUS:0028809451
SN - 0041-008X
VL - 135
SP - 58
EP - 66
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 1
ER -