Details

Autor(en) / Beteiligte

• Lopez, Adam

Titel

Non-genomic Control of Neuronal Calcium Signaling by the Steroid Hormone Estrogen Leads to Neuroprotective Effects

Ort / Verlag

ProQuest Dissertations Publishing

Erscheinungsjahr

2020

Link zum Volltext

• ProQuest

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• It has been well documented that the onset of menopause correlates with an increase in the onset of neurodegenerative diseases such as Alzheimer’s disease. Estrogen supplementation was used as treatment/prevention for a variety of medical conditions ranging from menopausal symptoms to major diseases, like Alzheimer’s disease. However, the field of estrogen neuroprotection has been fraught with controversy ever since a meta-analysis of clinical data, and large sample randomized placebo controlled long-term studies, revealed hormone replacement therapy may have little, none, or detrimental effects on brain health. These studies found differences in health benefits versus risks amongst women who received hormone replacement therapy, depending on age, length of reproductive viability, and the amount of time between estrogen decline to the start of treatment. Many studies have shown a link between estrogenic protection and the correction of calcium imbalance caused by ryanodine receptor malfunction. The estrogen receptor is thought to elicit this estrogenic protection by acting as a nuclear transcription factor and increasing the expression of anti-apoptotic proteins. However, the estrogen receptor also has non-genomic effects, and the changes occur too quickly after stimulus to have resulted from transcriptional changes. Although the genomic effects are well characterized, the non-genomic effects remain largely unexplored. One such effect is unliganded estrogen receptor β’s ability to affect calcium mobilization. My thesis project explored the following hypothesis: In the absence of its ligand estrogen receptor β binds ryanodine receptors 2/3, potentiating calcium release from intracellular stores. Immunocytochemistry confocal microscopy experiments showed that estrogen deprivation caused an increase in ERβ and RyR2/3 colocalization, suggesting an interaction would be possible in living neuronal cells. Coimmunoprecipitation confirmed the existence of this interaction. Calcium mobilization experiments showed a correlation between the ERβ/RyR2/3 interactions and increased calcium dyshomeostasis.