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GAMMA‐DIKETONE PERIPHERAL NEUROPATHY—II. NEUROFILAMENT SUBUNIT CONTENT
Author(s) -
Chiu Fc,
Opanashuk La,
He Dk,
Lehning Ej,
LoPachin Rm
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1529-8027.2000.22-52.x
Subject(s) - axon , neurofilament , atrophy , sciatic nerve , protein subunit , peripheral neuropathy , chemistry , endocrinology , medicine , tibial nerve , peripheral , axoplasmic transport , anatomy , biology , biochemistry , immunohistochemistry , stimulation , gene , diabetes mellitus
Quantitative morphometric analyses have demonstrated that axon atrophy is the primary neuropathic alteration in peripheral nerve of 2,5‐hexanedione (HD)‐intoxicated rats (Lehning et al., Toxicol. Appl. Pharmacol. 165, 127–140, 2000). Research suggests that axon caliber is regulated by neurofilament (NF) content and density. Therefore, as a possible mechanism of atrophy, NF subunit (NF‐L, ‐M, and ‐H) proteins were quantitated in moderately affected rats intoxicated with HD at three daily dosing rates (175, 250, and 400 mg/kg/day). Analyses of subunit protein contents in proximal sciatic nerves indicated uniformly small decreases, which corresponded to minimal changes in axon area occurring in this region. In distal tibial nerve, subunit proteins were decreased substantially (40–70%) when rats were exposed to the 175 and 250 mg/kg/day doses. These reductions in NFs corresponded to significant decreases (approximately 50%) in tibial axon area induced by lower dosing rates. In contrast, 400 mg/kg/day produced similar changes in caliber but smaller reductions (18–25%) in NF‐L, ‐M, and ‐H levels. This suggests that a decrement in axonal NF content is unlikely to be solely responsible for gamma‐diketone‐induced axon atrophy and that the corresponding mechanism probably involves additional changes in factors regulating NF density. Analysis of NF content in peripheral nerve also identified the presence of anomolous higher molecular weight NF‐H proteins. However, the neurotoxicological significance of these abnormal subunits is uncertain based on their limited occurrence and inconsistent spatiotemporal expression.