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

Abstract

Background Aβ 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 IFNβ1a 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 Aβ 1-42 peptide (23 μg/2 μl). After 6 days, 3.6 μg of IFNβ1a 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 IFNβ1a was able to reverse memory impairment and to counteract microglia activation and upregulation of pro-inflammatory cytokines (IL-6, IL-1β) in the hippocampus of Aβ 1-42 -injected rats. The anti-inflammatory cytokine IL-10, significantly reduced in the Aβ 1-42 animals, recovered to control levels following IFNβ1a treatment. IFNβ1a also reduced ROS and lipids peroxidation and increased SOD1 protein levels in the hippocampus of Aβ 1-42 -injected rats. Conclusion This study shows that IFNβ1a is able to reverse the inflammatory and cognitive effects of intra-hippocampal Aβ 1-42 in the rat. Given the role played by inflammation in AD pathogenesis and the established efficacy of IFNβ1a 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 Aβ deposition in the hippocampus of AD patients.

Inhibition of formyl peptide receptors improves the outcome in a mouse model of Alzheimer disease

“…Aβ acts as danger-associated molecular patterns (DAMP) which can bind to different DAMPreceptors, among FPR, which are expressed by microglia and astrocytes [13,14,25,27]. Aß binding to its receptors induced the expression of various pro-inflammatory mediators [68]. In addition, Aβ has been shown to be cleared by microglia in vitro and in vivo through receptor-mediated phagocytosis and degradation [69,70].…”

Myeloproliferative blood cancers as a human neuroinflammation model for development of Alzheimer’s disease: evidences and perspectives

“…First, the hypothesis calls for MPN-mutation screening studies among patients with AD and in patient populations which we know have an increased risk of AD as well. Second, considering that treatment with interferon-alpha2 (IFN) normalizes elevated blood cell counts within weeks in the large majority of patients with early stage MPNs (ET, PV, and hyperproliferative myelofibrosis) [63] and interferon-beta most recently has shown potent anti-inflammatory activity in concert with improvement in cognitive function in AD patients [64] and in a rat model [65], studies of the safety and efficacy of interferon-alpha or beta in a larger series of AD patients, preferentially those with early stage disease, might be timely and relevant taking into account that no agents so far have been able to revert disease activity in this devastating disease. Of note, IFN treatment may also impact key factors of utmost pathogenetic importance for AD development, including downregulation of upregulated oxidative stress genes and upregulation of downregulated antioxidative defence genes [66].…”

Inhibition of formyl peptide receptors improves the outcome in a mouse model of Alzheimer disease

“…Aβ acts as danger associated molecular patterns (DAMP) which can bind to different DAMP-receptors, among FPR, which are expressed by microglia and astrocytes (13,14,25,27). Aß binding to its receptors induced the expression of various pro-inflammatory mediators (68). In addition, Aβ has been shown to be cleared by microglia in vitro and in vivo through receptor-mediated phagocytosis and degradation (69,70).…”