Effect of aluminum and other multivalent cations on neurofilaments in vitro: An electron microscopic study

Using electron microscopy (EM) of negatively stained samples, we have systematically explored the effect of aluminum and other multivalent cations on neurofilaments (NFs) in vitro. Interactions of these cations were investigated with bovine, rabbit, and rat spinal cord native NFs, and with 10-nm filaments reconstituted from the 68-kDa subunit (NF-L) isolated from bovine spinal cord. Our results indicated that, as has been observed with other classes of intermediate filaments (IFs), all multivalent cations caused significant aggregation of native NFs, suggesting that this phenomenon is a rather general one and not limited to aluminum. In addition, all cations tried caused significant lateral aggregation of filaments reconstituted from NF-L. Aluminum lactate had an identical effect on bovine, rabbit, and rat NFs. Because aluminum causes strong aggregation of NFs in vitro, a similar phenomenon may occur in vivo leading to the observed accumulation of NFs in neuronal perikarya of rabbits after intoxication with aluminum. These in vitro observations support the concept that some human neurological diseases characterized by the accumulation of NFs may be related to abnormal levels of multivalent cations.