Impaired retention in AβPP Swedish mice six months after oral exposure to chlorpyrifos

Chlorpyrifos (CPF) is an organophosphate pesticide. This pesticide induces cognitive impairments, oxidative stress and neuronal damage, which suggests a possible relationship between CPF exposure and Alzheimer's disease. In this study we examined long-term changes in behavior and brain levels of the amyloid beta (Aβ) protein after repeated CPF exposure in a mouse model of Alzheimer's disease. Tg2576 male mice between four and six months of age carrying the human Swedish mutation for Alzheimer's disease were exposed to eight doses of 25 mg/kg of CPF distributed over four weeks. Five months after exposure, general activity was measured in an open-field, while learning and memory were assessed in a Morris water maze task six months after treatment with CPF. Levels of the Aβ fragments (1-40 and 1-42) were also measured in the frontal cortex and hippocampal brain regions. Motor activity was increased in CPF-exposed mice. Although acquisition learning in a water maze task was not affected, retention was worsened in CPF-exposed mice. There were no significant increases of Aβ levels in the brains of CPF-treated mice six months after exposure. These findings raise concerns about the risk of developing neurodegenerative diseases in vulnerable subjects following repeated exposure to CPF.