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Dale W. Sickles Background: Tangles of cytoskeletal fibers known as neurofilaments (NF) are a common occurrence in the brains of patients with Alzheimers's disease. Preventing the formation of these plaques of material has been a focus of research for a possible treatment of neurodegenerative diseases. NF accumulation occurs before or during the development of disease symptoms suggesting a cause and effect relationship; however, a direct test of this theory is lacking in the scientific literature. Acrylamide (ACR) and 2,5-hexanedione (HD) are known neurotoxiciants that cause the formation of NF formation in the axons of brain cells. ACR is an industrial chemical used to make plastics. HD is a product of the metabolism of hexane, a commonly used agent in chemical manufacturing. However, there is no direct evidence that NF formation caused by exposure to either of these compounds causes the death of nervous tissue. Advance: To provide a direct test of the necessity of NF formation for nerve cell dysfunction, this laboratory used transgenic mice missing the gene for NF formation thus rendering them incapable of accumulating NFs after exposure to ACR and HD. The non-transgenic mice used as controls in the experiment had normal NF development after exposure. The results demonstrate no difference in symptoms or pathology between the transgenic mice and non-transgenic controls. Implication: The authors conclude that NF formation is not necessary for nerve cell dysfunction seen after exposure to ACR and HD. The findings suggest that other structures in the neurons may be the targets for ACR and HD induced pathology and that the relevance of NF formation to disease progression warrants further discussion and interpretation. Publication: Stone JD, Peterson AP, Eyer J, Oblak TG, Sickles DW. Neurofilaments are nonessential to the pathogenesis of toxicant-induced axonal degeneration. J Neurosci. 2001 Apr 1;21(7):2278-87. |
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