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.

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Acknowledgments

The study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Programa Nacional de Cooperação Acadêmica; Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq 406715/2013-0]; Fundação de Amparo a Pesquisa do Espírito Santo; Fundo Estadual de Ciência e Tecnologia [39767531/07]; and Pró-reitoria de Pesquisa - Universidade Federal do Pampa [Nº 10.134.14]. The authors would like to thank Professor Christopher Exley from Keele University, Staffordshire, UK, for the support on GFAAS.

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Correspondence to Caroline S. Martinez or Giulia A. Wiggers.

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Martinez, C.S., Alterman, C.D.C., Peçanha, F.M. et al. Aluminum Exposure at Human Dietary Levels for 60 Days Reaches a Threshold Sufficient to Promote Memory Impairment in Rats. Neurotox Res 31, 20–30 (2017). https://doi.org/10.1007/s12640-016-9656-y

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Keywords

  • Aluminum
  • Cognitive dysfunction
  • Cholinergic dysfunction
  • Oxidative stress