T. Kihira et al., ALUMINUM-INDUCED MODEL OF MOTOR-NEURON DEGENERATION - SUBPERINEURIAL INJECTION OF ALUMINUM IN RABBITS, Neurotoxicology, 16(3), 1995, pp. 413-424
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.