ALUMINUM-INDUCED MODEL OF MOTOR-NEURON DEGENERATION - SUBPERINEURIAL INJECTION OF ALUMINUM IN RABBITS

Environmental factors, particularly chronic exposure to aluminum (Al) and manganese (Mn) with dietary deficiency of calcium (Ca) and magnesi um (Mg), are speculated to be contributory in the pathogenesis of amyo trophic lateral sclerosis (ALS). However, the mechanisms by which thes e elements accumulate in the CNS tissues and induce neuronal death are not known. In the present study, we investigated the retrograde trans port of Al as a possible mechanism of pathogenesis. Al (as aluminum ch loride or maltol) was injected into the subepineurial space of the sci atic nerve with subsequent morphological evaluation of the neurotoxic effect on spinal motor neurons in rabbits. Spheroids/globules, central and peripheral chromatolysis, and neuronal degeneration were observed in the spinal anterior horn in Al-maltol, Al chloride, and maltol tre ated rabbits to more marked extent than those in uninjected or saline controls. By electron microscopy, the soma and dendrites of neurons in the anterior horn at the fifth lumbar spinal cord in the Al-treated r abbit showed marked edematous change, fragmentation of granular endopl asmic reticulum, increased accumulation of neurofilament, and accumula tion of free ribosomes and lipid-droplet-like structures. Horseradish peroxidase (HRP) reactive product was seen in the axons and cytoplasm of Schwann cells of the sciatic nerve in Al-maltol treated rabbits, su ggesting that the permeability of the blood-nerve-barrier was increase d by injection of Al-maltol. We suggest that Al, subperineurially inje cted, was absorbed into the spinal cord and induced degeneration of sp inal motor neurons in these rabbits. These findings indicate that the retrograde transport of Al into spinal motor neurons via the periphera l nervous system may exacerbate neuronal degeneration in ALS. (C) 1995 Intox Press, Inc.