Inhibitor of cyclooxygenase-2 protects against amyloid beta peptide-evoked memory impairment in mice.
Journal Title: Pharmacological Reports - Year 2007, Vol 59, Issue 2
Abstract
Alzheimer's disease (AD) results in an impairment of memory and behavior. It is accepted that amyloid beta (Abeta) peptides are responsible for the etiopathology of AD, but the precise signaling pathways leading to the disease have not been elucidated. In this study, we have investigated the role of cyclooxygenase-2 (COX-2) in Abeta(1-42)-evoked memory impairment in mice. Moreover, the effect of systemic inflammation on Abeta-dependent locomotor and memory disturbances has been evaluated. Twelve-month-old C57Bl6 mice were injected intracerebroventricularly (icv) with Abeta(1-42) alone or simultaneously with intraperitoneal (ip) administration of lipopolysaccharide (LPS). Some mice also received COX-2 inhibitor, NS-398. Another group of mice was pretreated with LPS at 4 and 7 months of age, and then injected with Abeta(1-42) at 12 months of age. All mice were subjected to behavioral tests one week after Abeta administration. COX-2 protein level was analyzed in the hippocampus using immunochemical method. Our data demonstrated that Abeta enhanced COX-2 protein level and decreased the locomotion and exploration in mice. Systemic inflammation elevated COX-2 immunoreactivity at an early stage after injection and intensified behavioral disturbances. Moreover, the object recognition in Abeta-treated mice was significantly affected compared to control mice. The administration of LPS simultaneously with Abeta worsened recognition performance. ACOX-2 inhibitor protected mice against memory deficit and locomotor disturbances. In LPS-pretreated animals, Abeta induced locomotor disturbances, but had no effect on memory and COX-2 level. Our results indicate that Abeta evokes enhancement of COX-2 protein level and memory deficit. Systemic inflammation modulates Abeta effect on the brain function. The COX-2 inhibitor protects the brain against Abeta-induced memory disturbances.
Authors and Affiliations
Magdalena Cąkała, Anna Malik, Joanna Strosznajder
Keywords
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