Exploring Hippocampal Changes in Ovariectomized Rats using Magnetic Resonance Elastography

Researcher(s)

  • Kaelin Penna, Biological Sciences, University of Delaware

Faculty Mentor(s)

  • Curtis Johnson, Biomedical Engineering, University of Delaware

Abstract

Hormonal changes during menopause lead to structural alterations in the brain, particularly in hippocampal subregions involved in memory and higher-order cognition. However, these changes are not well characterized, making it challenging to distinguish between the effects of menopause, normal aging, and early neurodegenerative disease. Magnetic Resonance Elastography (MRE) is a noninvasive imaging technique that quantifies brain tissue stiffness and damping ratio (relative viscosity). It is emerging as a promising tool for studying neurodegenerative diseases, including Alzheimer’s disease, which disproportionately affects women. To support the development of MRE-based biomarkers for neurodegeneration, we sought to isolate and identify menopause-specific effects on brain tissue properties using a rodent model. This approach allowed us to separate menopause-related changes from those associated with aging or disease. We hypothesized that estrogen loss after menopause would elevate hippocampal damping ratio.

We performed unilateral ovariectomies (UOVX; n=8) to model perimenopause, bilateral ovariectomies (BOVX; n=8) to model menopause, and sham surgeries (n=8) for use as control animals. MRE scans were acquired pre-operatively and one month post-operatively using a rat-specific protocol to assess tissue mechanics and compute hippocampal stiffness and damping ratio. Data collection is ongoing, though preliminary findings suggest significant divergent mechanical changes depending on surgical condition: UOVX rats showed an average of 9.1% increase in damping ratio in the dorsal hippocampus, while BOVX rats exhibited an average of 20.8% decrease in damping ratio in the same region. We expect this may be due to responses to dynamic changes in estrogen levels and estrogen receptors in  perimenopause and menopause. Future work will include immunohistochemical analysis to identify cellular correlates of the observed mechanical changes, helping to clarify how menopause may contribute to altered brain structure.