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Intranasally Administered S100A9 Amyloids Induced Cellular Stress, Amyloid Seeding, and Behavioral Impairment in Aged Mice
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Department of General Chemistry, Sumy State University, Sumy, Ukraine.ORCID iD: 0000-0002-1691-9025
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Department of Pathology, Sumy State University, Sumy, Ukraine .ORCID iD: 0000-0002-2342-0337
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2018 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 9, no 6, p. 1338-1348Article in journal (Refereed) Published
Abstract [en]

Amyloid formation and neuroinflammation are major features of Alzheimer's disease pathology. Proinflammatory mediator S100A9 was shown to act as a link between the amyloid and neuroinflammatory cascades in Alzheimer's disease, leading together with Aβ to plaque formation, neuronal loss and memory impairment. In order to examine if S100A9 alone in its native and amyloid states can induce neuronal stress and memory impairment, we have administered S100A9 species intranasally to aged mice. Single and sequential immunohistochemistry and passive avoidance behavioral test were conducted to evaluate the consequences. Administered S100A9 species induced widespread cellular stress responses in cerebral structures, including frontal lobe, hippocampus and cerebellum. These were manifested by increased levels of S100A9, Box, and to a lesser extent activated caspase-3 immunopositive cells. Upon administration of S100A9 fibrils, the amyloid oligomerization was observed in the brain tissues, which can further exacerbate cellular stress. The cellular stress responses correlated with significantly increased training and decreased retention latencies measured in the passive avoidance test for the SI00A9 treated animal groups. Remarkably, the effect size in the behavioral tests was moderate already in the group treated with native S100A9, while the effect sizes were large in the groups administered S100A9 amyloid oligomers or fibrils. The findings demonstrate the brain susceptibility to neurotoxic damage of S100A9 species leading to behavioral and memory impairments. Intranasal administration of S100A9 species proved to be an effective method to study amyloid induced brain dysfunctions, and 5100A9 itself may be postulated as a target to allay early stage neurodegenerative and neuroinflammatory processes.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018. Vol. 9, no 6, p. 1338-1348
Keywords [en]
Aged mice, amyloid, apoptosis, BAX, activated caspase-3, cellular stress, learning and memory, neuroinflammation, S100A9
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-150871DOI: 10.1021/acschemneuro.7b00512ISI: 000436211800016PubMedID: 29618200Scopus ID: 2-s2.0-85048764488OAI: oai:DiVA.org:umu-150871DiVA, id: diva2:1244784
Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2018-09-03Bibliographically approved

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Iashchishyn, Igor A.Moskalenko, Roman A.Wang, ChaoMorozova-Roche, Ludmilla A.

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Iashchishyn, Igor A.Moskalenko, Roman A.Davydova, Tatiana, VWang, ChaoSewell, Robert D. E.Morozova-Roche, Ludmilla A.
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Department of Medical Biochemistry and Biophysics
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