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dc.contributor.advisorBoehm, Gary
dc.contributor.authorWiles, Jenna
dc.date2015-05-01
dc.date.accessioned2016-02-19T15:38:54Z
dc.date.available2016-02-19T15:38:54Z
dc.date.issued2015
dc.identifier.urihttps://repository.tcu.edu/handle/116099117/10461
dc.description.abstractIn the present study, we examined the protective effects of inverse benzodiazepine agonist MRK-016 on the cognitive deficits associated with inflammation-induced accumulation of amyloid-beta (A-beta), to model Alzheimer's disease-like pathology. We used a 2 x 2 design to test the ability of MRK-016 to protect against cognitive deficits resultant from an increase in A-beta in the hippocampus. We utilized a seven-day injection model of LPS on C57BL/6 mice to increase levels of A-beta. On day 8, we trained animals in a contextual fear conditioning paradigm to associate a conditioned stimulus (CS) with an unconditioned stimulus (US). MRK-016 was administered immediately after training to examine its effects on the consolidation stage of learning. Testing occurred on day 9, 24 hours after training, and the percentage of time the animal spent freezing was evaluated as an indication of learned association. Analysis of the behavioral data revealed a significant interaction between MRK-016 and LPS and between-groups analyses revealed that animals in the LPS/Saline condition froze significantly less during testing when compared to all other conditions. To elucidate the biological mechanism mediating the behavioral data, we collected the dorsal hippocampus from comparable animals 4 hours after training for analysis of Arc and TrkB gene expression using RT-PCR on collected tissue samples. We did not find evidence for any change in Arc expression. However, we did identify that animals in the LPS/Saline condition expressed significantly less TrkB mRNA than all other groups. Overall, these results indicate that MRK-016 has the ability to prevent A-beta-induced cognitive decrements in a hippocampus-dependent memory paradigm.
dc.subjectMRK-016
dc.subjectAlzheimer's disease
dc.subjectLPS
dc.titleEffects Of Mrk-016 On Amyloid-Beta Induced Learning Deficits In Mice In Contextual Conditioning Paradigm
etd.degree.departmentPsychology
local.collegeCollege of Science and Engineering
local.collegeJohn V. Roach Honors College
local.departmentPsychology


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