Type of Thesis
Psychology & Neuroscience
Dr. Michael Stowell
Dr. Jerry Rudy
Dr. Heidi Day
Dr. Ryan Bachtell
A mouse model of Alzheimer’s disease (AD), which overexpress the human amyloid precursor protein (APP), experience Kainic Acid (KA) induced seizures that are more severe than wild type (WT) mice. The latency and severity of seizures observed in AD mice are similar to those of Synaptophysin knockout (Syp KO) mice. Addition of amyloid plaques (Aβ) to cells in vitro leads to the breakdown of Syp-VAMP2 complex. In the present study, we investigated if the breakdown of Syp-VAMP2 complex is responsible for the observed seizure activity in AD mice. The binding of cholesterol to Syp is necessary for biogenesis of synaptic vesicles, and cholesterol-depleted cells have reduced Syp-VAMP2 complex. Being deficient in cholesterol, we expected to observe seizure susceptibility and also reduced Syp-VAMP2 complex in Apolipoprotein E4 (ApoE4) mice as well. We tested WT, AD, ApoE4, and Syp KO mice for susceptibility to KA induced seizures. Our findings revealed that AD, ApoE4, and Syp KO mice all have similar seizure severity and latency. Using western blot analysis we examined the levels of Syp-VAMP2 complex present in the brains of these mice at 6 months but we failed to observe a difference. We are currently devising more sensitive methods for measuring the abundance of the Syp-VAMP2 complex in the brain.
Amini, Maryam, "Comorbidity between Alzheimer’s Disease and Seizure Episodes" (2016). Undergraduate Honors Theses. 1016.
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