Establishment of a New Rat Model of Alzheimer's Disease Using Copper Sulfate

Copper is of great importance for the normal brain. Excess of copper results in neurodegenerative diseases such as Alzheimers disease (AD). The pathological hallmarks of AD are the amyloid- (A) peptides. A peptides have been shown to bind copper with high affinity. We established a new rat model of AD by using copper sulfate (CuSO4) solution with several doses and for different periods of time. The rats were randomly divided into normal control groups and AD groups. All rats underwent behavioral, histopathological and biochemical evaluations. The results of behavioral test revealed a significant improvement in the normal control groups. Conversely, AD groups showed impairments in the cognitive function as well as spatial memory with several degrees according to the duration and dose of CuSO4 administration. The precise dose of CuSO4 that showed the most cognitive deficits was 6 mg/L for eight weeks. Histochemistry staining revealed neuronal abnormalities in the brain sections of AD groups with several degrees. Biochemical analysis demonstrated that the level of -secretase was highest at a dose 6 mg/L CuSO4 for eight weeks, conversely, the level of -secretase was lowest at the same dose. We conclude that copper appeared to have a role in the formation of senile plaques, the hall mark of AD. According to these issues, we established a new rat model of AD using CuSO4 solution.