Effects of estradiol, tamoxifen, and raloxifene on human temporal lobe cortex astroglial cell spreading
Year: 2026
Type: article
Abstract: BACKGROUND: Astrocytes, once regarded as passive support cells, are recognized as active regulators of synaptic organization and neuronal integration. Through extension or retraction of their processes, astrocytes influence synapse formation and elimination. Astrocytes express estrogen receptors, and animal studies have shown that estradiol modifies astrocytic morphology in relation to synaptic density. OBJECTIVE: To examine the effects of estradiol and two clinically available selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene on astrocyte processes in human brain tissue. METHODS: Human temporal lobe cortical slices were incubated for 60 min with estradiol (10 nM), tamoxifen (1.0 µM), or raloxifene (1.0 µM), and the results were compared with untreated control slices. Astrocytes were visualized by immunostaining for the glial cytoskeletal marker glial fibrillary acidic protein (GFAP). Light microscopy image analysis was used to quantify astrocytic process thickness and branching, using Neurolucida® software. RESULTS: = 0.01 for primary processes). Estradiol treatment resulted in intermediate reductions in astroglial process measures that did not reach statistical significance. CONCLUSIONS: Estradiol, tamoxifen, and raloxifene - widely used hormonal agents - were associated with distinct effects on astrocyte morphology in human cortical tissue. These findings support a role for estrogen receptor modulation in astroglial structural regulation and suggest a potential cellular mechanism contributing to central nervous system symptoms reported in clinical settings.
Source: Gynecological Endocrinology
Authors: Ivaldo Silva, Frederick Nicholas Naftolin, Vinicius Oliveira Santana, Anne Williamson, Ahmed Fadiel, Dennis Spencer, Howard J. Li
Institutions: Indiana University Bloomington, Indiana University, Universidade Federal de São Paulo, Yale University, University of Chicago, University of Chicago Medicine Comprehensive Cancer Center, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
Award: G1304302508
OpenAlex ID: W7125415484
