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dc.contributor.authorWatremez, W.*
dc.contributor.authorJackson, J.*
dc.contributor.authorAlmari, B.*
dc.contributor.authorMcLean, Samantha L.*
dc.contributor.authorGrayson, B.*
dc.contributor.authorNeilla, J.C.*
dc.contributor.authorFischer, N.*
dc.contributor.authorAllouche, A.*
dc.contributor.authorKoziel, V.*
dc.contributor.authorPillot, T.*
dc.contributor.authorHarte, M.K.*
dc.date.accessioned2018-02-26T17:12:11Z
dc.date.available2018-02-26T17:12:11Z
dc.date.issued2018-02
dc.identifier.citationWatremez W, Jackson J, Almari B et al (2018) Stabilized low-n amyloid-ß oligomers induce robust novel object recognition deficits associated with inflammatory, synaptic, and GABAergic dysfunction in the rat. Journal of Alzheimer’s Disease. 62(1): 213-226.en_US
dc.identifier.urihttp://hdl.handle.net/10454/15087
dc.descriptionYesen_US
dc.description.abstractBackground:With current treatments for Alzheimer’s disease (AD) only providing temporary symptomatic benefits, disease modifying drugs are urgently required. This approach relies on improved understanding of the early pathophysiology of AD. A new hypothesis has emerged, in which early memory loss is considered a synapse failure caused by soluble amyloid-β oligomers (Aβo). These small soluble Aβo, which precede the formation of larger fibrillar assemblies, may be the main cause of early AD pathologies. Objective:The aim of the current study was to investigate the effect of acute administration of stabilized low-n amyloid-β1-42 oligomers (Aβo1-42) on cognitive, inflammatory, synaptic, and neuronal markers in the rat. Methods:Female and male Lister Hooded rats received acute intracerebroventricular (ICV) administration of either vehicle or 5 nmol of Aβo1-42 (10μL). Cognition was assessed in the novel object recognition (NOR) paradigm at different time points. Levels of inflammatory (IL-1β, IL-6, TNF-α), synaptic (PSD-95, SNAP-25), and neuronal (n-acetylaspartate, parvalbumin-positive cells) markers were investigated in different brain regions (prefrontal and frontal cortex, striatum, dorsal and ventral hippocampus). Results:Acute ICV administration of Aβo1-42 induced robust and enduring NOR deficits. These deficits were reversed by acute administration of donepezil and rolipram but not risperidone. Postmortem analysis revealed an increase in inflammatory markers, a decrease in synaptic markers and parvalbumin containing interneurons in the frontal cortex, with no evidence of widespread neuronal loss. Conclusion:Taken together the results suggest that acute administration of soluble low-n Aβo may be a useful model to study the early mechanisms involved in AD and provide us with a platform for testing novel therapeutic approaches that target the early underlying synaptic pathology.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.3233/JAD-170489en_US
dc.rights© 2018 IOS Press. Reproduced in accordance with the publisher's self-archiving policy. The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-170489en_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectAmyloid-β oligomers
dc.subjectCognition
dc.subjectParvalbumin
dc.subjectInterneurons
dc.titleStabilized low-n amyloid-ß oligomers induce robust novel object recognition deficits associated with inflammatory, synaptic, and GABAergic dysfunction in the raten_US
dc.status.refereedYesen_US
dc.date.Accepted2017-11-28
dc.date.application2018-02-06
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
refterms.dateFOA2018-07-28T03:17:16Z


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