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Mouse Model Behavior in APP/PS1 Mice Treated with a BBB-penetrating Erythropoietin Fusion Protein, cTfRMAb-EPO

Alzheimer’s disease (AD) is a devastating neurodegenerative condition in which a patient’s cognitive functioning, memory, and physical health progressively deteriorate. In order to treat physiological deterioration in AD, a neuroprotective recombinant human- erythropoietin (EPO) fusion protein was used. In addition to its ability to target amyloid beta (Aβ) aggregation, EPO has been shown to reduce inflammation, oxidative stress and synaptic loss. Recombinant human-erythropoietin (EPO) was combined with a chimeric transferrin receptor (TfR) monoclonal antibody (cTfRMAb) to form a fusion protein (cTfRMAb-EPO) that is able to cross the blood-brain barrier (BBB) by binding to the TfR expressed on the luminal side of the BBB. Thirty eight male APPswePSEN1dE9 (APP/PS1) mice were separated into four treatment groups (wildtype (WT) treated with saline, APP/PS1 treated with saline (TG), APP/PS1 treated with cTfRMAb-EPO (cTfRMAb-EPO), and APP/PS1 treated with rHu-EPO alone (rhu-EPO)) and were subcutaneously injected with their respective treatments twice a week for six weeks. Recognition memory and locomotive behavior were tested through the novel object recognition (NOR) task and open field (OF) test when the mice were 8 months old and again at 11 months old (after 8 weeks of treatment) to determine treatment effects. Both behavioral tests demonstrated a clear age effect in mice between 8- and 11-months old. In the NOR task, no significant differences in recognition memory were observed in TG, cTfRMAb-EPO, or rHu-EPO groups. Lastly, the OF test demonstrated no significant behavioral differences among treatment groups.

Identiferoai:union.ndltd.org:CLAREMONT/oai:scholarship.claremont.edu:cmc_theses-3068
Date01 January 2019
CreatorsWhitman, Kathrine
PublisherScholarship @ Claremont
Source SetsClaremont Colleges
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceCMC Senior Theses
Rights@2018 Kathrine M Whitman, default

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