title: Comparative study of chronic aluminum-induced neurofilamentous aggregates with intracytoplasmic inclusions of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is characterized neuropathologically by chromatolysis, Bunina bodies, hyaline inclusions, skein-like inclusions and axonal spheroids. Aluminum, a known neurotoxin, is the cause of dialysis encephalopathy and is considered to be a causative agent in high incidence foci of ALS in the western Pacific. We have developed an experimental model of motor neuron degeneration in New Zealand white rabbits using chronic low-dose intracisternal administration of aluminum and compared the clinical and neuropathological changes to those of human ALS. Aluminum-inoculated rabbits developed progressive hyperreflexia, hypertonia, limb splaying, gait impairment, muscle wasting, hindlimb paralysis and impaired tonic immobility responses without overt encephalopathic features over a 14-month period. Examination of spinal cords from these animals demonstrated the frequent occurrence and progressive development of anterior horn cell lesions that included small, round, argentophilic perikaryal inclusions similar to hyaline inclusions seen in human ALS. Other inclusions were more condensed and eosinophilic, while still others had neurofibrillary tangle-like morphologies. Axonal spheroids and neuritic thickenings were also prominent and were identical to those seen in human ALS. We believe that the similar and progressive development of neuropathological changes observed in the chronic aluminum-intoxication model, compared to human ALS, warrants further study to aid in understanding the cellular and molecular mechanisms of human motor neuron disease.
authors.affiliation: Research Center of Neurological Diseases, Kansai College of Oriental Medicine, Osaka, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Wakayama
authors.forename: V R
authors.initials: VR
authors.lastname: Nerurkar
authors.forename: M J
authors.initials: MJ
authors.lastname: Strong
authors.forename: R M
authors.initials: RM
authors.lastname: Garruto
mesh_terms: D000535:Aluminum / Q000506:poisoning*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure*; D008854:Microscopy, Electron; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D000535:Aluminum