Josselyn Barahona
The Effects of N-acetylcysteine on the Inflammatory Response of Alzheimer’s Disease Induced by Amyloid β-Peptide Oligomers
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Project Proposal:
I propose to study Alzheimer’s Disease in Chile, a country with a high rate of age-related dementia. Under the mentorship of Dr. Hidalgo and Dr. Lima, I will be studying the effects of oral administrations of NAC on the inflammatory response induced by amyloid β-peptide oligomers (AβΟs) in vivo and in vitro. We hypothesize that oral administrations of NAC will suppress the AβOs-induced inflammatory process seen in Alzheimer’s Disease and thereby attenuate neuronal degradation. I will spend the first two months establishing the functional role of microglia and astrocytes in AβOs-induced neuro-inflammation in a rodent model of Alzheimer’s Disease. To do so, I will study the morphologic and genetic changes these immune cells experience when under oxidative stress through immunohistochemistry and QPCR analysis respectively.
The following month, I will determine the baseline expression levels of two main inflammatory cytokines, tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6), secreted by these immune cells using ELIZA assays and Western Blots. After that, I plan to spend three months determining whether NAC treatments exert protective effects on the inflammatory process associated with Alzheimer’s Disease in a rodent model of Alzheimer’s Disease. During this time, I will treat the rodent model of Alzheimer’s Disease with oral administration of NAC. Then, I will analyze the changes oral treatments of NAC exert on the morphology and gene expression of microglia and astrocytes under oxidative stress through immunohistochemistry and QPCR analysis. The following month, I will study the changes NAC treatments exert on the levels of TNFα and IL-6 secreted by microglia and astrocytes.
From November to December, I will define the gene expression and cytokine profile of hippocampal neurons under oxidative stress using a neuronal cell culture model of Alzheimer’s Disease. I will spend a month determining the baseline expression levels of TNFα and IL-6 secreted by the hippocampal cells using ELIZA assays and QPCR analysis. I will spend the last month studying changes in the expression levels of TNFα and IL-6 after the neuronal cells are treated with NAC. Together, the findings of these experiments will not only define the neuroinflammatory response seen in Alzheimer’s Disease but will also shed light on the therapeutic potential of NAC for neurodegenerative diseases.
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Proposal:
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