How sodium arsenite improve amyloid β-induced memory deficit?

- Opposite dose dependent effects of sodium arsenite on contextual and tone memory
- Sodium arsenite at ultra-low doses attenuate memory impairment in Aβ injected rats.
- Sodium arsenite in high doses induced memory deficit 9 and 16 days after infusion.
- Alterations of CREB, Caspase3, Nrf2, HO-1 and NF-κB by sodium arsenite treatment

Evidence has shown that arsenic exposure, besides its toxic effects results in impairment of learning and memory, but its molecular mechanisms are not fully understood. In the present study, we examined sodium arsenite (1, 5, 10, 100 nM) effects on contextual and tone memory of male rats in Pavlovian fear conditioning paradigm alone and in co-administration with β-amyloid. We detected changes in the level of caspase-3, nuclear factor kappa-B (NF-κB), cAMP response element-binding (CREB), heme oxygenase-1 and NF-E2-related factor-2 (Nrf2) by Western blot. Sodium arsenite in high doses induced significant memory impairment 9 and 16 days after infusion. By contrast, low doses of sodium arsenite attenuate memory deficit in Aβ injected rats after 16 days. Our data revealed that treatment with high concentration of sodium arsenite increased caspase-3 cleavage and NF-κB level, 9 days after injection. Whereas, low doses of sodium arsenite cause Nrf2 and HO-1 activation and increased CREB phosphorylation in the hippocampus. These findings suggest the concentration dependent effects of sodium arsenite on contextual and tone memory. Moreover, it seems that the neuroprotective effects of ultra-low concentrations of sodium arsenite on Aβ-induced memory impairment is mediated via an increase Nrf2, HO-1 and CREB phosphorylation levels and decrease caspase-3 and NF-κB amount.