Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease
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 th...
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doaj-1f875c8cf3e6439cb3203200e50450b72020-11-25T03:37:12ZengBMCJournal of Neuroinflammation1742-20942019-02-0116111610.1186/s12974-019-1417-4Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s diseaseGiuseppa Mudò0Monica Frinchi1Domenico Nuzzo2Pietro Scaduto3Fulvio Plescia4Maria F. Massenti5Marta Di Carlo6Carla Cannizzaro7Giovanni Cassata8Luca Cicero9Maria Ruscica10Natale Belluardo11Luigi M. Grimaldi12Department of Biomedicine, Neuroscience and Advanced Diagnostics, Division of Human Physiology, University of PalermoDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, Division of Human Physiology, University of PalermoInstitute of Biomedicine and Molecular Immunology “Alberto Monroy” (IBIM), Consiglio Nazionale delle Ricerche (CNR)Department of Biomedicine, Neuroscience and Advanced Diagnostics, Division of Human Physiology, University of PalermoDepartment of Sciences for Health Promotion and Mother and Child Care “Giuseppe D’Alessandro”, University of PalermoDepartment of Sciences for Health Promotion and Mother and Child Care “Giuseppe D’Alessandro”, University of PalermoInstitute of Biomedicine and Molecular Immunology “Alberto Monroy” (IBIM), Consiglio Nazionale delle Ricerche (CNR)Department of Sciences for Health Promotion and Mother and Child Care “Giuseppe D’Alessandro”, University of PalermoExperimental Zooprophylactic Institute of Sicily “A. Mirri”Experimental Zooprophylactic Institute of Sicily “A. Mirri”Neurology Department, Fondazione Istituto Giuseppe GiglioDepartment of Biomedicine, Neuroscience and Advanced Diagnostics, Division of Human Physiology, University of PalermoNeurology Department, Fondazione Istituto Giuseppe GiglioAbstract 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.http://link.springer.com/article/10.1186/s12974-019-1417-4IFNβ1aNeuroinflammationROSPro-inflammatory cytokinesSODAβ1-42 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease Journal of Neuroinflammation IFNβ1a Neuroinflammation ROS Pro-inflammatory cytokines SOD Aβ1-42 |
author_facet |
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 |
author_sort |
Giuseppa Mudò |
title |
Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease |
title_short |
Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease |
title_full |
Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease |
title_fullStr |
Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease |
title_full_unstemmed |
Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease |
title_sort |
anti-inflammatory and cognitive effects of interferon-β1a (ifnβ1a) in a rat model of alzheimer’s disease |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2019-02-01 |
description |
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. |
topic |
IFNβ1a Neuroinflammation ROS Pro-inflammatory cytokines SOD Aβ1-42 |
url |
http://link.springer.com/article/10.1186/s12974-019-1417-4 |
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