DOSE-DEPENDENT SELECTIVE SUPPRESSION OF LIGHT (NFL) AND MEDIUM (NFM) BUT NOT HEAVY (NFH) MOLECULAR-WEIGHT NEUROFILAMENT MESSENGER-RNA LEVELS IN ACUTE ALUMINUM NEUROTOXICITY

We inoculated 5- to 6-week old New Zealand white rabbits intracisterna lly with either 100, 250, 500, 750, or 1000 mug of AlCl3 or 0.9% NaCl and correlated the extent of cervical motor neuron neurofilamentous in clusion formation at 48 h postinoculation with alterations in neurofil ament (NF) mRNA levels. RNA was isolated from cervical spinal cord by the guanidine isothiocyanate method and individual RNA samples were no rmalized for poly(A+) content. Northern blot analysis was performed wi th cDNA probes for light (NFL), medium (NFM), and heavy (NFH) neurofil ament subunit protein or with oligonucleotide probes for alpha-tubulin or actin. No significant alteration in the levels of alpha-tubulin, a ctin, or NFH mRNA were observed, regardless of the aluminum dose. In c ontrast, dose-dependent reductions in NFL and NFM mRNA levels occurred in direct proportion to the extent of neurofilamentous inclusion form ation. While inoculums of NaCl or 100 or 250 mug AlCl3 induced neither inclusion formation or alterations in mRNA levels, both inclusion for mation and reductions in the levels of NFL and NFM mRNA occurred there after, becoming maximal with inoculums of 1000 mug AlCl3. These experi ments indicate that intracisternally administered AlCl3 acutely suppre sses NFL and NFM mRNA levels without affecting those of NFH. This patt ern is in distinct contrast to the uniform reductions of all NF mRNA t ranscript levels during neurogenesis or following axotomy, indicating a specific effect of aluminum upon steady-state levels of NF mRNA that correlates with the induction of neurofilamentous aggregates. (C) 199 4 Academic Press, Inc.