Aluminum-induced neuropathology: transient changes in microtubule-associated proteins.
In susceptible species, aluminum induces cytoskeletal changes in which neurofilaments accumulate in neuronal cell bodies and proximal axonal enlargements. To determine if microtubule-associated proteins (MAPs) are altered in this model, we examined the spinal cords of aluminum- and saline-treated control rabbits at several time points after treatment. Transient decreases in tau and MAP2 immunoreactivity in neurons in aluminum-intoxicated rabbits were demonstrated with immunocytochemistry. An antibody directed against Alzheimer's disease paired helical filaments labeled neurons in aluminum-treated rabbits but not controls. MAP5 immunoreactivity in the cell body cytoplasm was displaced by aluminum-induced tangles. The transient decreases in MAP2 and tau immunoreactivity did not reflect alterations in protein levels measured using immunoblotting. The transient antigenic changes in tau and MAP2 may reflect conformational changes in these cytoskeletal proteins. Aluminum-induced pathology provides a model for studying perturbations in MAPs and neurofilament proteins that are characteristic of many human neurodegenerative diseases such as Alzheimer's disease, diffuse Lewy body disease, Parkinson's disease, and amyotrophic lateral sclerosis.
Muma
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Department of Pharmacology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA. nmuma@wpo.it.luc.edu
Singer
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SM
D000535:Aluminum / Q000633:toxicity*; D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis
D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D016875:tau Proteins; D000535:Aluminum