Does estrogen show neuroprotective effects on hypothalamic cells when induced by beta amyloid?

Alzheimer's disease (AD) is a neurodegenerative disorder that results in 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. Estrogen has shown to have neuroprotective effects on AD in the hippocampus. The literature is unclear of the role of the hypothalamus in AD although early pathophysiology of AD, such as disturbances in sleep and emotional affect has been observed. 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. 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. Treatment on N38 cells with beta-amyloid 42 treated with estrogen at dosages similar or higher than physiologically concentrations, will be done at various time points. Cell lysis and cytotoxicity of beta-amyloid 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.