title: p,p'-Methoxyl-diphenyl diselenide protects against amyloid-β induced cytotoxicity in vitro and improves memory deficits in vivo.
abstract: Behavioral evidence suggests that the organoselenium compound p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)2] ameliorates memory and learning performance in rodents. Here, we investigated the molecular mechanism of (MeOPhSe)2 neuroprotection in cortical neurons exposed to amyloid-β (Aβ) peptide as well as in Aβ-infused mice. For this purpose, primary cultures of rat cortical neurons were pre-incubated with 10 μM of (MeOPhSe)2 or vehicle, followed by exposure to 25 μM Aβ fragment 25-35 or vehicle. Furthermore, the therapeutic effect of (MeOPhSe)2 (5 mg/kg, oral route, daily for 5 days) on memory deficits was evaluated in mice exposed to Aβ fragment 25-35 (3 nmol/3 μl/per site, intracerebroventricular infusion). The results demonstrate that (MeOPhSe)2 prevented Aβ-induced cell death in vitro, associated with inhibition of caspase-3 and -9 activities, poly (ADP-ribose) polymerase (PARP) cleavage and c-Jun N-terminal kinase (JNK) activation. Further, (MeOPhSe)2 rescued Aβ-induced memory impairment in mice. In conclusion, (MeOPhSe)2 is neuroprotective in vitro and in vivo, suggesting that this organoselenium compound offers a potential treatment option for Alzheimer's disease.
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: Simone
authors.initials: S
authors.lastname: Pinton
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Souza
authors.forename: Marcel H M
authors.initials: MH
authors.lastname: Sari
authors.forename: Rita M
authors.initials: RM
authors.lastname: Ramalho
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003603:Cytotoxins / Q000633:toxicity; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D001555:Benzene Derivatives; D003603:Cytotoxins; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C528548:p-methoxy-diphenyl diselenide; D053148:Caspase 3