Aluminum neurotoxicity: altered expression of cytoskeletal genes

Abstract

To better understand perturbations of the neuronal cytoskeleton that occur in several mammalian disorders, we have focused on an animal model in which neurofibrillary pathology follows the administration of aluminum salts. In susceptible species, the injection of aluminum produces accumulations of neurofilaments (NFs) in cell bodies and proximal axons of certain populations of neurons. Mechanisms involved in the production of these abnormalities are unclear; in particular, the role of gene expression in the genesis of this type of neurofibrillary pathology has not been examined. In this study of aluminum-intoxicated rabbits, the expression of genes coding for several cytoskeletal proteins was studied in the spinal cord and dorsal root ganglia (DRG)--tissues with and without neurofibrillary pathology, respectively. In aluminum-treated rabbits, in situ hybridization using a cDNA probe demonstrated the presence of mRNA coding for the 68-kDa NF (NF-L) protein in spinal cord motor neurons with NF accumulations as well in unaffected neurons. On Northern blots, the expression of genes coding for the NF-L protein and tubulin was reduced by approximately 3.5-fold and 3-fold, respectively, in spinal cords of aluminum-intoxicated rabbits as compared to controls. On blots, levels of actin mRNA were not significantly different in spinal cords of aluminum-treated rabbits as compared to controls, but there was a trend for a slight reduction. In DRG of intoxicated animals, the expression of genes coding for these cytoskeletal proteins was not altered.