Sub-chronic exposure to diazinon induce cognitive impairment, alternations in amyloid precursor proteins, and TNF-α expression in the hippocampus of adult rats

Abstract

Abstract Organophosphate pesticides such as diazinon (DZN) are involved in the development of psychological symptoms and memory deficits but their effects on the amyloid precursor proteins (APP) genes expression remains unclear. Following low-level oral exposure to the DZN (2 mg/kg), we used novel object recognition, open field, and elevated plus-mazes (EPM) to assess memory and anxiety-like behaviors in rats. We also evaluated alteration in the levels of tumor necrosis factor (TNF-α), amyloid precursor protein (APP), and APP-like protein-2 (APLP2) and real-time quantitative PCR to evaluate the expression of the related genes in the hippocampus. The results showed that DZN exposure increased anxiety-like behaviors, regardless of the duration of exposure, but only extended exposure (12 weeks) impaired memory. The study also found that the hippocampal expression of APP and APLP2 decreased after 12 weeks of exposure, but not after 5 days. The TNF-α gene was up-regulated following 5 days of exposure, but 12 weeks of exposure had no effect. Our finding demonstrates that long-lasting exposure to low levels of DZN in adulthood stimulates APP degradation, which may contribute to poor cognitive outcomes. Given that APP plays a significant role in Alzheimer's disease pathogenesis, alterations in APP expression could contribute to dementia.