A Purine Derivative Containing an Organoselenium Group Protects Against Memory Impairment, Sensitivity to Nociception, Oxidative Damage, and Neuroinflammation in a Mouse Model of Alzheimer's Disease

In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (A beta) (25-35 fragment), 3 nmol/3 mu l/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). A beta caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-kappa B (NF-kappa B), and the proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in cerebral cortex and hippocampus. Additionally, A beta increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-kappa B in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by A beta. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease.

Automated summary

In this study, the researchers found that treatment with FSP can alleviate memory impairment and sensitivity to pain caused by Aβ, by exerting its effects against oxidative stress and neuroinflammation.