The effects of chronic copper exposure on the amyloid protein metabolisim associated genes' expression in chronic cerebral hypoperfused rats

The pathogens of Alzheimer's disease (AD) are still unclear, while accumulating evidences have indicated that both genetic and environmental factors are involved in the pathogenesis of AD. Recent studies suggest that AD is primarily a vascular disorder and copper (Cu) may play an important role in AD pathology. However, the consequences of chronic Cu exposure at the presence of other AD risk factors remain to be clarified. To investigate the effects of chronic Cu intake on cerebral hypoperfusion-induced AD pathology, Sprague-Dawley rats suffered bilateral common carotid artery occlusion (2VO) were administrated with 250 ppm copper-containing water or not. Morris water maze test showed that Cu exposure for 3 months exacerbated cognitive impairment induced by 2VO. Elevated amyloid precursor protein (APP) and beta-site APP-cleaving enzyme 1 (BACE1) expression in mRNA and protein levels were also observed in brain of Cu-exposed rats suffered 2VO. In contrast, these Cu-exacerbated changes were ameliorated after Cu was withdrawn from drinking water. In summary, our findings demonstrate that chronic Cu exposure might exacerbate AD pathology in 2VO rats.

► Copper exacerbated cognitive impairment in cerebral hypoperfused rats. ► Copper increases the expressions of APP and BACE1 in the brain from cerebral hypoperfused rats. ► Copper increases the amyloid protein in the brain from cerebral hypoperfused rats.