Neuroprotective Effects of Estrogen on Beta‐Amyloid Induced Neurotoxicity in Murine Hypothalamic Cells

Abstract

Alzheimer’s disease (AD) is a neurodegenerative affliction marked by significant cognitive decline and eventual dementia. The two most notable pathological hallmarks of AD include beta‐amyloid plaques, formed from the extracellular aggregation and deposition of beta‐amyloid fibrils, and the intracellular accumulation of hyperphosphorylated tau as neurofibrillary tangles in the brain. Previous research has suggested a possible neuroprotective property of estrogen, the female sex hormone, in AD. Despite the implications of a hypothalamic role in the early pathophysiology of AD, such as disturbances in sleep and emotional affect, scant literature exists outside of cortical and hippocampal AD research. This study is designed to replicate AD models using a control cell line, SH‐SY5Y human neuroblastoma cells, and an experimental cell line, N38 murine hypothalamic cells in culture, by incubating these cells with oligomerized human beta‐amyloid 42 (Aβ42). Each cell line is then treated with estrogen in order to observe the hormone’s efficacy as a neuroprotective agent. Cell viability, cytotoxicity and proliferation were measured in order to determine estrogen’s neuroprotective potential, using a variety of bioassays such as MTT and LDH. Preliminary results show lower mitochondrial activity and higher rates of cell lysis when treated with physiologically relevant concentrations of estrogen and low beta‐amyloid concentrations in the SH‐SY5Y cell line. In addition, the low concentration of Aβ42 (10μmol) appeared to have neuroproliferative effects on the SH‐SY5Y cells as opposed to its expected neurotoxicity. Conversely, N38 cells treated with estrogen at dosages higher than physiologically relevant concentrations, were found to have higher mitochondrial activity than cells treated with only Aβ42 after 24 hours, indicating a possible neuroprotective effect of estrogen at high concentrations on the hypothalamic cell line. Cell lysis and cytotoxicity of Aβ42 in N38 cells will be tested in order to further elucidate the pathology of the hypothalamus in AD, as well as estrogen’s potential neuroprotective effect on this unexplored brain region.Support or Funding InformationBiology Department, Adelphi University, Garden City, New York. Department of Biological Sciences, New York City College of Technology/CUNY, New York, NY.