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Chlorpyrifos (CPF) is an organophosphate pesticide widely used in intensive agriculture. Various studies have demonstrated delayed neurotoxic effects in adult mammals after acute CPF exposure. This pesticide induces oxidative stress and neuronal damage, which suggests a possible relationship between CPF exposure and Alzheimer's disease (AD). In the present study, we examined in a mice model of AD, long-term changes in the behavior and brain levels of amyloid β after acute CPF exposure. Fifty mg/kg of CPF were subcutaneously injected to Tg2576 (Tg) mice carrying the Swedish amyloid-β protein precursor (AβPP) mutation for AD. General status, body weight, acetyl cholinesterase (AChE) inhibition, and behavioral changes were assessed. Amyloid β fragment (1-40 and 1-42) levels were also measured in the cortical and hippocampal brain regions. A significant and transient decrease in body weight was observed 72 hr after treatment, while no autonomic effects were noted. Motor activity was decreased in Tg mice seven months after CPF treatment. Acquisition learning in a water maze task was not affected, but retention was ameliorated in CPF-exposed Tg mice. Amyloid β levels increased in the brains of treated Tg mice eight months after CPF exposure. The results of this study show that some behavioral changes persisted or emerged months after acute CPF exposure, while amyloid β levels increased. These findings raise concern about the risk of developing neurodegenerative diseases following moderate exposure to CPF in vulnerable subjects.

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.