Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor
Year: 2022
Type: article
Abstract: In breast cancer patients, behavioral comorbidities reduce quality of life, increase mortality, and may persist years into remission. These side effects are associated with increased circulating and brain inflammatory markers in patients and rodent tumor models, respectively. The prevalence and severity of these behavioral comorbidities stratify by menopausal status, suggesting an underlying mechanistic role of estrogen. Here, we manipulated “menopause” status (ovary-intact and ovariectomized) in a mouse mammary tumor model to determine the extent to which ovarian status modulates: 1) tumor effects on estrogen concentrations and signaling in the brain, 2) tumor effects on estrogen-associated neurobiology and inflammation, and 3) the ability for tumor resection to resolve the effects of a tumor. As estrogens are anti-inflammatory and beneficial to cognitive and emotional behavior, we hypothesized that reduced circulating estradiol (E2) following ovariectomy exacerbates tumor-induced peripheral and central inflammation. Notably, we observed ovarian-dependent modulation on tumor-induced peripheral outcomes, including E2-dependent processes and, to a lesser degree, circulating inflammatory markers. In the brain, ovariectomy exacerbated neuroinflammatory markers in select brain regions and modulated E2-related neurobiology due to a tumor and/or resection. Overall, our data suggest that ovarian status has moderate implications for tumor-induced alterations in neuroendocrinology and neuroinflammation and mild effects on peripheral inflammatory outcomes in this murine mammary tumor model.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4292595258