Date of Award
Martin Margittai, Ph.D.
Aging, Alzheimer's disease, Immunocal, Neurodegeneration, Oxidative stress, Reelin
Deficits in Reelin expression and signaling play a pathogenic role in Alzheimer’s disease (AD). Thus, strategies aimed at correcting Reelin deficits may provide a novel therapeutic approach to treating AD. The cysteine-rich, whey protein supplement, Immunocal®, has recently been shown to rescue Reelin expression in a mouse model of Schizophrenia. Given that Reelin-expressing neurons of the entorhinal cortex region are a highly vulnerable population of cells that are lost early in AD, we examined the effects of Immunocal® in the hippocampal-entorhinal cortex formation in a mouse model of AD. Glutathione levels and Reelin expression in the hippocampal-entorhinal cortex formation (entorhinal cortex, EC; dentate gyrus, DG; and Cornu Ammonis, CA1/ Cornu Ammonis, CA3 regions of hippocampus) of 12-month old hAPPSweInd mice were significantly reduced when compared to non-carrier controls as measured by HPLC, western blot and immunohistochemistry respectively. These reductions were prevented in hAPPSweInd mice when treated with Immunocal® from 3 month to 12-month-old. We assessed the transcript levels of Reelin using in situ hybridization and show a reduction in Reelin transcript levels in untreated hAPPSweInd mice compared to non-carrier mice; However, Immunocal® treatment preserved Reelin transcript levels. Elevating Reelin expression through treatment with Immunocal® significantly reduced the number, size and density of Amyloglo stained amyloid plaques throughout the hippocampal-entorhinal cortex formation. Our findings demonstrate that Immunocal® rescues Reelin expression in vivo within the hippocampal-entorhinal cortex formation of 12-month-old transgenic hAPPSweInd mice. This rescue of Reelin expression was associated with an amelioration of the pathological amyloid plaque load. To our knowledge, these data provide the first evidence of a therapeutic agent that is capable of correcting Reelin deficits in the hAPPSweInd mouse model of AD. Our findings support the testing of Immunocal® as a novel therapeutic agent for patients suffering from Alzheimer’s disease.
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Puttagunta, Srivalli, "Amelioration of Alzheimer's Disease Pathology in 12-Month-Old hAPP(SweInd) Transgenic Mice After Treatment with a Cysteine Rich Whey Supplement, Immunocal®" (2019). Electronic Theses and Dissertations. 1683.
Received from ProQuest
Molecular biology, Cellular biology