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Our rodent mammary tumor model recapitulates aspects of these behavioral sequelae, as well as elevated circulating and brain inflammatory mediators. Neuroinflammation is a proposed mechanism underlying the etiology of mood disorders and cognitive deficits, and therefore may be contributing to tumor\u2010associated behavioral side effects. The cellular mechanisms by which tumor\u2010induced neuroinflammation occurs remain unknown, making targeted treatment approaches inaccessible. Here, we tested the hypotheses that microglia are the primary cells driving tumor\u2010induced neuroinflammation and behavioral side effects. Young adult female BALB\/c mice were induced with a 67NR mammary tumor; tumor\u2010free controls underwent a sham surgery. Mammary tumors increased IBA1\n                    <jats:sup>+<\/jats:sup>\n                    and GFAP\n                    <jats:sup>+<\/jats:sup>\n                    staining in the amygdala and hippocampus relative to tumor\u2010free controls. However, tumors did not alter gene expression of Percoll\u2010enriched microglia isolated from the whole brain. While cognitive, social, and anhedonia\u2010like behaviors were not altered in tumor\u2010bearing mice, tumors increased central tendency in the open\u2010field test; microglia depletion did not reverse this effect. Brain region RT\u2010qPCR data indicated that microglia depletion attenuated tumor\u2010induced elevations of neuroinflammatory gene expression in a region\u2010 and mediator\u2010specific manner. These results indicate a causal role of microglia in tumor\u2010induced neuroinflammation. This research advances our understanding of the cellular mechanisms underlying tumor\u2010induced neuroinflammation in order to understand how brain responses (e.g., behavior) may be altered with subsequent cancer\u2010related immune challenges.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301580rr","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T10:59:13Z","timestamp":1705575553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Microglia contribute to mammary tumor\u2010induced neuroinflammation in a female mouse model"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-4231","authenticated-orcid":false,"given":"Lindsay D.","family":"Strehle","sequence":"first","affiliation":[{"name":"Institute for Behavioral Medicine Research Ohio State University Wexner Medical Center  Columbus Ohio 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