Anti-inflammatory and cognitive effects of interferon-?1a (IFN?1a) in a rat model of Alzheimer's disease

Giuseppa Mudò, Monica Frinchi, Domenico Nuzzo, Pietro Scaduto, Fulvio Plescia, Maria F. Massenti, Marta Di Carlo, Carla Cannizzaro, Giovanni Cassata, Luca Cicero, Maria Ruscica, Natale Belluardo, Luigi M. Grimaldi

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Background: Aβ1-42 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 Aβ1-42 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 Aβ1-42-injected rats. The anti-inflammatory cytokine IL-10, significantly reduced in the Aβ1-42 animals, recovered to control levels following IFNβ1a treatment. IFNβ1a also reduced ROS and lipids peroxidation and increased SOD1 protein levels in the hippocampus of Aβ1-42-injected rats. Conclusion: This study shows that IFNβ1a is able to reverse the inflammatory and cognitive effects of intra-hippocampal Aβ1-42 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.

Original languageEnglish (US)
Article number44
JournalJournal of neuroinflammation
Volume16
Issue number1
DOIs
StatePublished - Feb 18 2019
Externally publishedYes

Keywords

  • Hippocampus
  • IFNβ1a
  • IL-10
  • Neuroinflammation
  • NF-kB
  • Pro-inflammatory cytokines
  • ROS
  • SOD

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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