title: Stress-Induced Alterations of Immune Profile in Animals Suffering by Tau Protein-Driven Neurodegeneration.
abstract: Alzheimer's disease (AD) is a multifactorial disorder; neurofibrillary pathology composed of tau protein is found side by side with amyloid-β deposits and extensive neuroinflammation. The immune system of the brain is considered as one of the factors that could influence the speed of the progression of AD neuropathology as a potential mediator of the damage induced by AD protein deposits. Alzheimer's disease pathology can be impacted by psychological stress; however, signalling pathways in background are not well known. We have explored possible avenues of how stress could influence the brain's immune system in a rat model of AD. Animals were subjected either to a single or multiple instances of immobilization stress. The analysis of a panel of immunity-related genes was used to evaluate the impact of stress on the immune response in the brain. We have identified 19 stress-responsive genes that are involved in neuroinflammation accompanying tau pathology: Nos2, Ptgs2, IL-8rb, C5, Mmp9, Cx3cr1, CD40lg, Adrb2, IL-6, IL-6r, IL-1r2, Ccl2, Ccl3, Ccl4, Ccl12, TNF-α, IL-1α, IL-1β, IL-10. Most of them are deregulated under the stress conditions also in control animals; however, the magnitude of the response to either acute or chronic stress differs. This can lead to serious influence, most probably to acceleration of neurodegenerative phenotype in diseased animals. Several of the genes (IL-1β, Casp1, Cx3cr1 and C5) are deregulated solely in tauopathic animals. The stress-induced changes in the inflammatory picture of the brain highlight the fact that the brain's immune response is highly responsive to environmental stimuli. The pattern of changes is indicative of an attempt to protect the brain in the short term, while being potentially detrimental to the response against a long-term pathological process such as neurofibrillary degeneration.
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.|AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
authors.forename: Petr
authors.initials: P
authors.lastname: Novak
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.|AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Cente
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Nina
authors.initials: N
authors.lastname: Kosikova
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Augustin
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.|Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Richard
authors.initials: R
authors.lastname: Kvetnansky
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.|AXON Neuroscience R&D Services SE, Bratislava, Slovakia.
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia. peter.filipcik@savba.sk.|AXON Neuroscience R&D Services SE, Bratislava, Slovakia. peter.filipcik@savba.sk.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0001-8919-5964
authors.initials: P
authors.lastname: Filipcik
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000378:metabolism / Q000523:psychology; D051381:Rats; D011918:Rats, Inbred SHR; D055647:Rats, Transgenic; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism / Q000523:psychology; D016875:tau Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D016875:tau Proteins
keywords: Immune markers; Neurodegeneration; Stress; Tau protein; Transgenic rat