Honors College Thesis
 

Ibuprofen Treatment Causes NMDA and AMPA Receptor Hyperactivity in Female Wild Type and Heterozygous 5xFAD mice but not Males

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https://ir.library.oregonstate.edu/concern/honors_college_theses/9g54xr58z

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  • With Alzheimer’s disease being the most prominent form of dementia, finding potential treatments for the disease is imperative. This study explored the non-steroidal anti-inflammatory drug ibuprofen as a potential treatment to normalize the hyperactive N-methyl-d-aspartate receptor (NMDAR) within the 5xFAD mice early in the disease pathology before cognitive decline. Female and male transgenic 5xFAD mice and wildtype mice on the C57BL/6 background were fed chow containing 375 ppm ibuprofen or normal chow between 2 to 4 months of age. At 4.5-5 months of age, the mice were euthanized, and multielectrode electrophysiological studies were done to compare the activity of NMDAR within the synapses of the Schaffer collateral axon/CA1 region of the hippocampus with the use of linear regression analysis of the input (fiber volley) / output (field excitatory post synaptic potentials) data. In corroboration with this lab’s previous studies, transgenic female (P<0.0001) and male (P<0.007) mice had hyperactive NMDAR responses compared to wildtype female and male mice, respectively. Interestingly, ibuprofen increased NMDAR responses compared to normal chow groups for female wildtype mice (P<0.0001) and female transgenic mice (P=0.0075). Male transgenic and wildtype mice treated with ibuprofen did not have altered NMDAR responses compared to normal chow groups. These results are the first to report sex differences in NMDAR responses arising from ibuprofen treatment in young female mice.
  • Key Words: NMDA receptor, electrophysiology, amyloid-beta, 5xFAD, NSAID
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  • Pending Publication
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  • 2022-06-01 to 2023-07-02

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