title: p-Chloro-diphenyl diselenide reverses memory impairment-related to stress caused by corticosterone and modulates hippocampal [(3)H]glutamate uptake in mice.
abstract: 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 (20μg/ml) in their drinking water during four weeks. In the last week, the animals were treated with (p-ClPhSe)2 (1 or 5mg/kg) by the intragastric route (i.g.) once a day for 7days. 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 [(3)H] glutamate uptake by hippocampal slices of mice treated with corticosterone. By contrast, [(3)H] 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 [(3)H]glutamate uptake in mice.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Zborowski
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Marcel H M
authors.initials: MH
authors.lastname: Sari
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Suélen O
authors.initials: SO
authors.lastname: Heck
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Eluza C
authors.initials: EC
authors.lastname: Stangherlin
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: José S S
authors.initials: JS
authors.lastname: Neto
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil. Electronic address: gzeni@ufsm.br.
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D003345:Corticosterone / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D011897:Random Allocation; D011930:Reaction Time / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D016566:Organoselenium Compounds; C574977:p-chloro-diphenyl diselenide; D014316:Tritium; D018698:Glutamic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D003345:Corticosterone
keywords: Glucocorticoids; Glutamate uptake; Memory; Organoselenium; Selenium