title: Ligand specific effects on aluminum incorporation and toxicity in neurons and astrocytes.
abstract: Aluminum is present in many manufactured foods and medicines and is added to drinking water for purification purposes. It has been proposed that aluminum is a contributing factors to several neurodegenerative disorders such as Alzheimer's disease. However, this remains controversial primarily due to the unusual properties of aluminum and a lack of information on its cellular sites of action. To resolve some of these questions, we have examined aluminum uptake in both neuronal and astroglial cells as well as the role of metal speciation. The relative accumulation of four aluminum salts, aluminum maltolate, aluminum lactate, aluminum chloride and aluminum fluoride, was investigated and correlated with cell viability and intracellular distribution as determined by morin staining. Significant differences in aluminum incorporation and toxicity were observed in both neuronal and glia cells with the largest effects exhibited by the maltol species. This was accompanied by a nuclear accumulation in the neuronal cell line that was contrasted by the perinuclear, vesicular distribution in astrocytes that partially co-localized with cathepsin D, a lysosomal marker. These findings demonstrate differences in aluminum species and highlights the importance of these factors in modulating the toxic effect of aluminum.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada M5S 3H2. ll5n@virginia.edu
authors.forename: L
authors.initials: L
authors.lastname: Lévesque
authors.forename: C A
authors.initials: CA
authors.lastname: Mizzen
authors.forename: D R
authors.initials: DR
authors.lastname: McLachlan
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects; D005459:Fluorides / Q000633:toxicity; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007773:Lactates / Q000633:toxicity; D008024:Ligands; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D009942:Organometallic Compounds / Q000633:toxicity; D011753:Pyrones / Q000633:toxicity; D051381:Rats
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D007773:Lactates; D008024:Ligands; D009498:Neurotoxins; D009942:Organometallic Compounds; D011753:Pyrones; C067527:aluminum maltolate; D000077410:Aluminum Chloride; D005459:Fluorides; C104223:aluminum lactate; C032311:aluminum fluoride