Piezo1 Receptor Expression on Glia and Brain Tissue Mechanics measured with MRE in Rodent Models of Perimenopause and Menopause

• Sneha Indrakanti, Neuroscience, University of Delaware
• Jose Abreu Mirabal, Neuroscience, University of Delaware

• Anna Y. Klintsova, Department of Psychological and Brain Sciences, University of Delaware
• Curtis L. Johnson, Department of Biomedical Engineering, Department of Psychological and Brain Sciences, University of Delaware

Declining estrogen during menopause causes peripheral tissues including breast, vaginal, and dermal tissue to lose elasticity and stiffness. Piezo1, a mechanosensitive ion channel that regulates collagen synthesis and extracellular matrix remodeling in response to tissue stiffness, may be modulated by estrogen signaling through the G protein-coupled estrogen receptor (GPER) pathway, yet its role in menopause-related tissue changes remains unexplored. Previous work in the Johnson Lab showed altered brain tissue viscoelasticity during low-estrogen states using  magnetic resonance elastography (MRE). Specifically, an inverse relationship was observed between hippocampal damping ratio and estrogen production. MRE is a noninvasive, in vivo MRI technique that uses induced vibrations to calculate tissue mechanical properties. We hypothesized that due to its sensitivity to hormonal fluctuations, hippocampal tissue mechanics would be altered in rodent models of perimenopause and menopause. Moreover, we predict that MRE results would be correlated with changes in Piezo1 expression on CA1 astrocytes, indicating altered mechanobiological tissue properties. Female rats in estropause underwent unilateral (UOVX) or bilateral (BOVX) ovariectomies modelling perimenopause and menopause, respectively, with undisturbed and sham surgery rats as controls. All rats were scanned before and 4 weeks post-surgery. Hippocampal damping ratio significantly increased by 23% in UOVX rats relative to sham controls (p<0.05), suggesting partial estrogen depletion induces changes in tissue viscoelasticity. Contrastingly, the BOVX group exhibited no significant change in hippocampal damping ratio, indicating that following complete estrogen loss, hippocampal mechanics mimic stable estrogen production environments. Ongoing histological quantification of Piezo1 receptor expression on astrocytes and oligodendrocytes will be compared between experimental groups and correlated with MRE findings. Nuclear versus cytoplasmic expression of Piezo1 will be compared between groups to determine how estrogenic fluctuation may alter receptor trafficking. This study will advance our understanding of brain tissue mechanics and underlying mechanobiological changes during the menopause transition.