Neurofilament degradation in the nervous system of rats intoxicated with acrylamide, related compounds or 2,5-hexanedione

Abstract

Degradation of neurofilament (NF) proteins by Ca2+-activated neutral protease (CANP) was studied in the nervous system of rats treated with neurotoxic or non-neurotoxic compounds. In the tibial nerve, the degradation of NF 68K was depressed by five neurotoxic compounds: acrylamide, N-hydroxymetylacrylamide, N-isopropylacrylamide, methacrylamide and 2,5-hexanedione. A non-neurotoxic compound, diacetone acrylamide, did not show any effect on the degradation. An immunoblot analysis confirmed the reduction in the degradation and revealed a difference in the degradation pattern between the control and acrylamide-treated rats. In the spinal cord, the degradation of the three subunits of NF was depressed in animals treated with acrylamide. Although the exact mechanism of the reduction in the degradation of NF is not yet known, the present results suggest that an inhibitory effect on CANP activity might be relevant to the mechanism of neurotoxic action of acrylamide derivatives.