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 magnesium (Mg), are speculated to be contributory in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, the mechanisms by which these elements accumulate in the CNS tissues and induce neuronal death are not known. In the present study, we investigated the retrograde transport of Al as a possible mechanism of pathogenesis. Al (as aluminum chloride or maltol) was injected into the subepineurial space of the sciatic nerve with subsequent morphological evaluation of the neurotoxic effect on spinal motor neurons in rabbits. Spheroid/globules, central and peripheral chromatolysis, and neuronal degeneration were observed in the spinal anterior horn in Al-maltol, Al chloride, and maltol treated 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 rabbit showed marked edematous change, fragmentation of granular endoplasmic reticulum, increased accumulation of neurofilament, and accumulation 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, suggesting that the permeability of the blood-nerve-barrier was increased by injection of Al-maltol. We suggest that Al, subperineurially injected, was absorbed into the spinal cord and induced degeneration of spinal motor neurons in these rabbits. These findings indicate that the retrograde transport of Al into spinal motor neurons via the peripheral nervous system may exacerbate neuronal degeneration in ALS.
Kihira
T
T
Division of Neurological Diseases, Wakayama Medical College, Japan.
Yoshida
S
S
Komoto
J
J
Wakayama
I
I
Yase
Y
Y
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008854:Microscopy, Electron; D016472:Motor Neuron Disease / Q000139:chemically induced*; D009410:Nerve Degeneration; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects / Q000648:ultrastructure
D000535:Aluminum