Impaired Spatial Learning and Unaltered Neurogenesis in a Transgenic Model of Alzheimers Disease After Oral Aluminum Exposure

Abstract

Although it is well established that aluminum (Al) is neurotoxic, the potential role of this element in the etiology of Alzheimer's disease (AD) is not well established. In this study, we evaluated the effects of oral Al exposure on spatial learning, memory and neurogenesis in Tg2576 mice, an animal model of AD in which Abeta plaques start to be deposited at 9 months of age. Aluminum was given as Al lactate (11 mg/g of food) for 6 months. At 11 months of age a water maze test was carried out to evaluate learning and memory. Subsequently, mice were injected with bromo-deoxyuridine (BrdU) and sacrificed 24 hours or 28 days after the last injection in order to assess proliferation, survival and differentiation of neurons. We observed impaired acquisition in the water maze task in Al-treated Tg2576 mice, as well as worse memory in the Al-exposed groups. In terms of neurogenesis, no effects of aluminum were observed in proliferation, survival and differentiation. The results of this investigation suggest that Tg2576 mice fed for 210 days with rodent chow supplemented with Al lactate at 11 mg/g of food have impaired spatial learning although their neurogenesis remains unmodified.

Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts

“…The Akiyama et al (2011) and Ribes (2010, 2011) data demonstrate that repeated high-dose Al ingestion increased brain Al concentrations, but increased brain Al failed to potentiate abnormal accumulation of Aβ, tau, or neuritic β-amyloid plaques in transgenic mouse models of AD. Since Al-induced pathology in rodent brain is different from that seen in AD (Wisniewski 1997, Klatzo et al 1965), extrapolation of studies in transgenic rodents to assessment of human health risks posed by Al is limited.…”

“…Three recent studies examined the potential toxicity of ingested Al in novel protocols that gave mice AlCl 3 or Al lactate for at least 90 days (Akiyama et al 2011, Ribes et al 2010, 2011). These assays are unique in that transgenic mice with increased amyloid β-protein (Aβ) deposition as a result of human Aβ precursor protein (AβPP) mutations (Tg2576) and (P301L) at the tau protein (Tg2576tau) were examined.…”

“…The Tg2576 mouse carries the Lys670→Asn,Met671→Leu mutation and by six months of age they develop a 5-fold increase in Aβ( 1–40 ) and a 14-fold increase in Aβ( 1–42/43 ). The Ribes et al (2010, 2011) protocols compared the responses seen in the Tg2576 mouse with those seen in wild-type mice. None of these studies examined more than one Al dose level.…”

“…In related protocols, Ribes et al (2010) fed Al lactate in a stock rodent chow to male wild-type and Tg2576 transgenic mice for 210 days. Ribes et al (2011) followed those studies by feeding dietary Al lactate to 15 male wild-type and 17 Tg2576 transgenic mice for 3 months.…”

“…Ribes et al (2010) evaluated learning, memory, and neurogenesis in 40 male wild-type and transgenic Tg2576 mice. Until 5 months of age, the animals had free access to laboratory chow containing 27 mg Al/kg and tap water containing 14 μg Al/L.…”