An Analysis of How Lead Induces Changes in Histone Modification Levels that Impact Alzheimer’s Disease Gene Expression
Patrikas, Maggie Zoe
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CitationPatrikas, Maggie Zoe. 2023. An Analysis of How Lead Induces Changes in Histone Modification Levels that Impact Alzheimer’s Disease Gene Expression. Master's thesis, Harvard University Division of Continuing Education.
AbstractThe goal of this study was to determine if lead exposure induced a histone epigenomic profile like that of Alzheimer’s Disease (AD) in differentiated SH-SY5Y neuroblastoma cells. AD is a neurological disease expressed as progressive memory loss and cognitive decline. The most common form of AD is Late Onset AD (LOAD) and it occurs in individuals > 65 years old. Longitudinal studies suggest genetics only account for approximately 70% of LOAD cases, suggesting that epigenetics plays a role (Gatz et al., 2005). Several previous studies have linked lead poisoning to AD pathology (Eid & Zawia, 2016; Reuben, 2018; Wu, Basha, Brock, et al., 2008). Here, SH-SY5Y cells were differentiated into more mature neurons and treated with lead acetate to induce lead exposure (Adwan et al., 2014; Kovalevich & Langford, 2013; Shipley et al., 2016). Antibodies were used to target specific histone modifications and isolate associated DNA. Next generation sequencing was used to measure changes in the levels of histone modifications previously linked to both lead exposure and AD. In this study, lead acetate did impact enrichment of regulatory histone marks at genes related to tau production and neural development. The most dramatic changes in enrichment levels were at SIRT1 which is involved in tau production, and SLC35D1 which is involved in neural development and brain damage repair. However, lead acetate did not appear to significantly effect histone mark enrichment at genes involved in Aβ development (APP, SP1, BACE1, or RTN4), suggesting lead acetate treatment had no significant effect on APP proteolysis in differentiated SH-SY5Y cells.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37375053
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