Potentiation of arsenic neurotoxicity by folate deprivation: protective role of S-adenosyl methionine.

Folate deficiency contributes to a variety of age-related neurological and psychological disorders including amyotrophic lateral sclerosis (ALS). The environmental neurotoxin arsenic has recently been linked with decreased neurofilament (NF) content in peripheral nerve. We examined herein, whether or not folate deprivation potentiated the impact of arsenic on NF dynamics. Arsenic inhibited translocation of NFs into axonal neurites in culture and increased perikaryal NF phosphoepitopes. Folate deprivation potentiated the impact of arsenic on these phenomena. Supplementation with S-adenosyl methionine (SAM) attenuated the impact of folate deprivation on arsenic neurotoxicity, consistent with the decrease in SAM following folate deprivation and the requirement for SAM-mediated methylation for arsenic bioelimination. These findings demonstrate how key nutritional deficiencies can potentiate the impact of enrivonmental neurotoxins.