TgF344-AD Rat Model of Alzheimer's Disease: Spatial Disorientation and Asymmetry in Hemispheric Neurodegeneration.

Autor:	Sagalajev B; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Stereotactic and Functional Neurosurgery, Cologne, Germany.; European Graduate School of Neuroscience (EURON), Maastricht, Netherlands., Lennartz L; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Stereotactic and Functional Neurosurgery, Cologne, Germany.; European Graduate School of Neuroscience (EURON), Maastricht, Netherlands., Vieth L; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Cologne, Germany.; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Jülich, Germany., Gunawan CT; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Stereotactic and Functional Neurosurgery, Cologne, Germany.; European Graduate School of Neuroscience (EURON), Maastricht, Netherlands., Neumaier B; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Cologne, Germany.; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Jülich, Germany., Drzezga A; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine, Cologne, Germany.; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Molecular Organization of the Brain (INM-2), Jülich, Germany., Visser-Vandewalle V; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Stereotactic and Functional Neurosurgery, Cologne, Germany.; European Graduate School of Neuroscience (EURON), Maastricht, Netherlands., Endepols H; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, Cologne, Germany.; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Jülich, Germany.; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine, Cologne, Germany., Sesia T; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Stereotactic and Functional Neurosurgery, Cologne, Germany.; European Graduate School of Neuroscience (EURON), Maastricht, Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease reports [J Alzheimers Dis Rep] 2023 Sep 26; Vol. 7 (1), pp. 1085-1094. Date of Electronic Publication: 2023 Sep 26 (Print Publication: 2023).
DOI:	10.3233/ADR-230038
Abstrakt:	Background: The TgF344-AD ratline represents a transgenic animal model of Alzheimer's disease. We previously reported spatial memory impairment in TgF344-AD rats, yet the underlying mechanism remained unknown. We, therefore, set out to determine if spatial memory impairment in TgF344-AD rats is attributed to spatial disorientation. Also, we aimed to investigate whether TgF344-AD rats exhibit signs of asymmetry in hemispheric neurodegeneration, similar to what is reported in spatially disoriented AD patients. Finally, we sought to examine how spatial disorientation correlates with working memory performance. Methods: TgF344-AD rats were divided into two groups balanced by sex and genotype. The first group underwent the delayed match-to-sample (DMS) task for the assessment of spatial orientation and working memory, while the second group underwent positron emission tomography (PET) for the assessment of glucose metabolism and microglial activity as in-vivo markers of neurodegeneration. Rats were 13 months old during DMS training and 14-16 months old during DMS testing and PET. Results: In the DMS task, TgF344-AD rats were more likely than their wild-type littermates to display strong preference for one of the two levers, preventing working memory testing. Rats without lever-preference showed similar working memory, regardless of their genotype. PET revealed hemispherically asymmetric clusters of increased microglial activity and altered glucose metabolism in TgF344-AD rats. Conclusions: TgF344-AD rats display spatial disorientation and hemispherically asymmetrical neurodegeneration, suggesting a potential causal relationship consistent with past clinical research. In rats with preserved spatial orientation, working memory remains intact. Competing Interests: The authors have no conflict of interest to report. (© 2023 – The authors. Published by IOS Press.)
Databáze:	MEDLINE
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