Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer's disease

Background: A beta(1-42) peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFN1 beta a in attenuating cognitive impairment and inflammation in an animal model of AD. Methods: A rat model of AD was obtained by intra-hippocampal injection of A beta(1-42) peptide (23 mu g/2 mu l). After 6 days, 3.6 mu g of IFN beta 1a was given subcutaneously (s.c.) for 12 days. Using the novel object recognition (NOR) test, we evaluated changes in cognitive function. Measurement of pro-inflammatory or anti-inflammatory cytokines, reactive oxygen species (ROS), and SOD activity levels was performed in the hippocampus. Data were evaluated by one-way ANOVA with Fisher's Protected Least Significant Difference (PLSD) test. Results: We showed that treatment with IFN beta 1a was able to reverse memory impairment and to counteract microglia activation and upregulation of pro-inflammatory cytokines (IL-6, IL-1 beta) in the hippocampus of A beta(1-42)-injected rats. The anti-inflammatory cytokine IL-10, significantly reduced in the A beta(1-42) animals, recovered to control levels following IFN beta 1a treatment. IFN beta 1a also reduced ROS and lipids peroxidation and increased SOD1 protein levels in the hippocampus of A beta(1-42)-injected rats. Conclusion: This study shows that IFN beta 1a is able to reverse the inflammatory and cognitive effects of intra-hippocampal A beta(1-42) in the rat. Given the role played by inflammation in AD pathogenesis and the established efficacy of IFN beta 1a in the treatment of inflammatory diseases of the central nervous system such as multiple sclerosis, its use may be a viable strategy to inhibit the pro-inflammatory cytokine and oxidative stress cascade associated with A beta deposition in the hippocampus of AD patients.