Researcher(s)
- Kaelin Penna, Biological Sciences, University of Delaware
- Meggan Bischoff, Neuroscience, University of Delaware
Faculty Mentor(s)
- Curtis Johnson, Biomedical Engineering, University of Delaware
- , , University of Delaware
Abstract
Hormonal changes during the reproductive years lead to structural alterations in the brain, including hippocampal subregions involved in memory and higher order cognition; however little is known about how microstructure is altered across extended hormonal transitions, i.e. menopause. While no current biomarkers exist to identify the stage of menopause (i.e., perimenopause, menopause, or post-menopause), precluding proper hormone replacement therapy (HRT) onset, they are critical for maximizing benefits and minimizing associated risks. A potential approach to fill this gap is magnetic resonance elastography (MRE), a noninvasive MRI technique that quantifies brain tissue stiffness and damping ratio (relative viscosity), and has been shown to correlate with cognitive capacity. In a previous study, the Johnson lab demonstrated that hippocampal damping ratio is elevated during natural or induced periods of low estrogen, suggesting that MRE can detect underlying changes to brain microstructure following estrogen fluctuation. It was determined that estrogen receptor alpha (ERα) expression on hippocampal astrocytes was upregulated during low estrogen states. To further understand estrogen’s influence on brain mechanics, we modeled perimenopause and menopause in rodents via unilateral (UOVX) and bilateral (BOVX) ovariectomy, respectively. We hypothesized that brain MRE might uncover changes to tissue mechanics in these models. Furthermore, we expected that fluctuations in hippocampal tissue mechanics measured with MRE would be associated with dynamic changes to astrocyte ERα expression, providing understanding of underlying cellular changes contributing to overall tissue properties during this transition. MRE results show a 23% increase in hippocampal damping ratio in UOVX rats compared to sham controls, while BOVX rats exhibited no significant difference. Thus, hippocampal mechanics experience a shift during perimenopause, and following complete estrogen loss, mimic stable estrogen production environments. Multi-label immunocytochemistry will quantify changes in astrocytes and estrogen receptors, visualized with primary antibodies, and tagged with fluorescent secondary antibodies. Data comparing ERα expression on astrocytes is ongoing; comparisons between cell and nuclear membrane receptors will investigate trafficking in both conditions.