Estrogen Modulation of Astrocyte Transcriptional Programs and Vascular Interactions in Health and Injury
Dr. Carmen Muñoz-Ballester, Department of Biological Sciences.
Estrogen loss during menopause is linked to blood-brain barrier (BBB) breakdown, which increases risk for neurological disease. The BBB protects the brain by tightly regulating the movement of molecules between the blood and brain tissue. Astrocytes support BBB function and respond to estrogen through estrogen receptors. Yet, whether estrogen levels influence BBB integrity through astrocyte signaling remains unknown. The objective of this project is to use transcriptomic databases to test the idea that estrogen-mediated regulation of the BBB is mediated by astrocytes. For this, we used RNA sequencing datasets from mouse brains and we studied estrogen-responsive genes in astrocytes and their relationship to BBB markers. We used datasets of mice with different estrogen levels, estrogen depletion, traumatic brain injury, and conditional ER knockout. Clustering, differential gene expression, pathway analysis, and other methods were used to predict communications between cell types to identify astrocyte genes altered via estrogen signaling. Understanding these links between estrogen, astrocytes, and BBB function is important for developing future strategies to protect brain health and lower risk of cognitive decline in people with changing hormone levels.