p-Chloro-diphenyl diselenide reverses memory impairment-related to stress caused by corticosterone and modulates hippocampal [H-3]glutamate uptake in mice

摘要

Chronic stress or chronically high levels of glucocorticoids can result in memory impairment. This study aimed to investigate if 4,4'-dichloro-diphenyl diselenide (p-ClPhSe)(2) reverses memory impairment related to stress caused by corticosterone administration in mice and its possible mechanism of action. Swiss mice received corticosterone (20 mu g/ml) in their drinking water during four weeks. In the last week, the animals were treated with (p-ClPhSe)(2) (1 or 5 mg/kg) by the intragastric route (i.g.) once a day for 7 days. The cognitive performance of mice was assessed through the object recognition test (ORT), the object location test (OLT) and the step-down passive avoidance test (SDPA), some of predictive tests of memory. Biochemical parameters were determined and locomotor activity of mouse was performed to gain insight in (p-ClPhSe)(2) toxicity. The findings demonstrated that treatment with (p-ClPhSe)(2) in both doses was effective in reversing memory deficits in the ORT, the OLT and the SDPA caused by corticosterone exposure in mice. Treatment with (p-ClPhSe)(2) at both doses reversed the increase in the 1411 glutamate uptake by hippocampal slices of mice treated with corticosterone. By contrast, [H-3] glutamate uptake by brain cortical slices was not altered in mice exposed to corticosterone. The Na+K+ ATPase activity was not altered in hippocampus and cerebral cortices of mice treated with corticosterone. There was no sign of toxicity in mice treated with (p-ClPhSe)(2). This organoselenium compound reversed memory impairment-related to stress caused by corticosterone and modulated hippocampal [H-3]glutamate uptake in mice. (C) 2016 Elsevier Inc. All rights reserved.