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Extended isolation stress induces exacerbation of Alzheimers Disease-related pathology in 5xFAD mice

Peterman, Julia Lauren
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2018
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The prevalence of Alzheimers Disease, a neurodegenerative disease characterized by the pathological hallmarks of amyloid beta (AB) plaques and neurofibrillary tangles, is increasing while its causes are unknown. Interestingly, stress can exacerbate AB production in transgenic mouse models of Alzheimers. We hypothesized that a social stressor, isolation stress, would exacerbate AB production in 5xFAD+ transgenic mice in comparison to group-housed control animals and 5xFAD- mice. Further, it was hypothesized that isolated, 5xFAD+ animals would freeze less in a contextual fear-conditioning (CFC) paradigm, a hippocampus-dependent memory task, than group housed, 5xFAD+ or isolated 5xFAD- animals. After extended isolation or group housing, animals underwent CFC, following which freezing behavior was monitored during testing 24 hours later. Twenty-four hours after testing, animals were perfused and a brain hemisphere was collected for sectioning and staining for plaques, while the hippocampus was removed from the other hemisphere and AB was quantified by an ABx-42 ELISA. Two and three months of isolation stress increased the number of AB plaques in the hippocampus of 5xFAD+ mice without significantly altering soluble AB levels. Animals isolated for 2 and 3 months also displayed a cognitive deficit in CFC.
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1 online resource (vi, 33 pages) :
Department
Psychology