title: Aluminum Exposure at Human Dietary Levels for 60 Days Reaches a Threshold Sufficient to Promote Memory Impairment in Rats.
abstract: Aluminum (Al) is a significant environmental contaminant. While a good deal of research has been conducted on the acute neurotoxic effects of Al, little is known about the effects of longer-term exposure at human dietary Al levels. Therefore, the purpose of this study was to investigate the effects of 60-day Al exposure at low doses for comparison with a model of exposure known to produce neurotoxicity in rats. Three-month-old male Wistar rats were divided into two major groups: (1) low aluminum levels, and (2) a high aluminum level. Group 1 rats were treated orally by drinking water for 60 days as follows: (a) control-received ultrapure drinking water; (b) aluminum at 1.5 mg/kg b.w., and (c) aluminum at 8.3 mg/kg b.w. Group 2 rats were treated through oral gavages for 42 days as follows: (a) control-received ultrapure water; (b) aluminum at 100 mg/kg b.w. We analyzed cognitive parameters, biomarkers of oxidative stress and acetylcholinesterase (AChE) activity in hippocampus and prefrontal cortex. Al treatment even at low doses promoted recognition memory impairment seen in object recognition memory testing. Moreover, Al increased hippocampal reactive oxygen species and lipid peroxidation, reduced antioxidant capacity, and decreased AChE activity. Our data demonstrate that 60-day subchronic exposure to low doses of Al from feed and added to the water, which reflect human dietary Al intake, reaches a threshold sufficient to promote memory impairment and neurotoxicity. The elevation of oxidative stress and cholinergic dysfunction highlight pathways of toxic actions for this metal.
authors.affiliation: Graduate Program in Biochemistry, Universidade Federal do Pampa, BR 472-Km 592, PO box 118, Uruguaiana, RS, 97500-970, Brazil. caroline.s.martinez@gmail.com.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Martinez
authors.affiliation: Graduate Program in Biochemistry, Universidade Federal do Pampa, BR 472-Km 592, PO box 118, Uruguaiana, RS, 97500-970, Brazil.
authors.forename: Caroline D C
authors.initials: CD
authors.lastname: Alterman
authors.affiliation: Graduate Program in Biochemistry, Universidade Federal do Pampa, BR 472-Km 592, PO box 118, Uruguaiana, RS, 97500-970, Brazil.
authors.forename: Franck M
authors.initials: FM
authors.lastname: Peçanha
authors.affiliation: Department of Physiological Sciences, School of Medicine of Santa Casa de Misericórdia (EMESCAM), Av. Nossa Senhora da Penha 2190, Vitória, ES, 29045402, Brazil.
authors.forename: Dalton V
authors.initials: DV
authors.lastname: Vassallo
authors.affiliation: Graduate Program in Biochemistry, Universidade Federal do Pampa, BR 472-Km 592, PO box 118, Uruguaiana, RS, 97500-970, Brazil.
authors.forename: Pâmela B
authors.initials: PB
authors.lastname: Mello-Carpes
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación, Campus Universitario de Cantoblanco, Nicolás Cabrera, 9, 28049, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Miguel
authors.affiliation: Graduate Program in Biochemistry, Universidade Federal do Pampa, BR 472-Km 592, PO box 118, Uruguaiana, RS, 97500-970, Brazil. giuliawp@gmail.com.
authors.forename: Giulia A
authors.initials: GA
authors.lastname: Wiggers
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000284:Administration, Oral; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014873:Water Pollutants / Q000633:toxicity; D014877:Water Pollution, Chemical
chemical_list: D000975:Antioxidants; D060766:Drinking Water; D017382:Reactive Oxygen Species; D014873:Water Pollutants; D000535:Aluminum; D000110:Acetylcholinesterase
keywords: Aluminum; Cholinergic dysfunction; Cognitive dysfunction; Oxidative stress