Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice

Barrientos, Ruth M.; Strehle, Lindsay D.; Lahoud, Ashley A.; Pyter, Leah M.

doi:10.1016/j.cpnec.2020.100002

Cited by 4 publications

(9 citation statements)

References 53 publications

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“…Tumors induce both systemic and brain in ammation, as evidenced by clinical and rodent studies, respectively [15,33,[68][69][70]. As we have previously reported in ovary-intact mice, here tumors elevated in ammatory markers in circulation [15,33,71]. This pattern was mirrored by elevated pro-in ammatory Il1b gene expression in all brain regions examined.…”

Section: Discussionsupporting

confidence: 61%

“…Fred Miller and Lisa Polin at Karmanos Cancer Institute. Cells were grown in DMEM with 10% FBS, 2 mM L-glutamine, 1mM non-essential amino acids, and 10% penicillin-streptomycin antibiotics at 37°C with 5% CO 2 [15,33].…”

Section: Introductionmentioning

confidence: 99%

“…Tumor surgeries. Syngeneic, orthotopic mammary tumors were induced in all Tumor and Resect groups while tumor-free Controls underwent the same surgery receiving an equivalent volume of phosphatebuffered saline (PBS), as previously described [15,33]. Tumors were induced in the Resect group (Surgery 1) approximately two weeks prior to the Tumor group to synchronize later tissue collection among all groups (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor

Strehle

Russart

Burch

et al. 2022

American Journal of Physiology-Regulatory, Integrative and Comp

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Breast cancer patients have increased circulating inflammatory markers and mammary tumors increase neuroinflammation in rodent models. Menopausal status is not only important in the context of breast cancer as circulating estrogen influences tumor progression, but also because estrogen is anti-inflammatory and an essential modulator of endocrine function in the brain and body. Here, we manipulated "menopause" status (ovary-intact and ovariectomized) in an ER+ 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. 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.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor

Strehle

Russart

Burch

et al. 2022

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Protein analyses of plasma determined that the potential confounding effects of CSF1R inhibition on circulating immunity were minimal in BALB/c mice (Figure S2). Indeed, PLX chow did not attenuate the previously reported tumor‐induced elevations in circulating markers 12,36,37 . Thus, the observed neuroinflammatory results were likely driven by the depletion of microglia and not a dampened peripheral‐to‐brain signal.…”

Section: Resultsmentioning

confidence: 65%

“…Plasma inflammatory markers (IL‐1β, IL‐6, TNF‐α, and C‐X‐C motif chemokine ligand 1 [CXCL1, also known as KC/GRO]) were measured using a multiplex immunoassay (U‐PLEX; Meso Scale Diagnostics, Rockville, MD, USA) according to the manufacturer's instructions on a QuickPlex SQ 120 instrument (Meso Scale Diagnostics). We have previously reported that this mammary tumor increases the concentrations of these mediators in circulation 11,36,37 . All samples were run in duplicate; wells that were undetectable for a particular analyte were excluded and the detectable well value for that sample was used.…”

Section: Methodsmentioning

confidence: 99%

Microglia contribute to mammary tumor‐induced neuroinflammation in a female mouse model

Strehle,

Otto‐Dobos,

Grant

et al. 2024

The FASEB Journal

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Following diagnosis but before treatment, up to 30% of breast cancer patients report behavioral side effects (e.g., anxiety, depression, memory impairment). 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‐associated behavioral side effects. The cellular mechanisms by which tumor‐induced neuroinflammation occurs remain unknown, making targeted treatment approaches inaccessible. Here, we tested the hypotheses that microglia are the primary cells driving tumor‐induced neuroinflammation and behavioral side effects. Young adult female BALB/c mice were induced with a 67NR mammary tumor; tumor‐free controls underwent a sham surgery. Mammary tumors increased IBA1+ and GFAP+ staining in the amygdala and hippocampus relative to tumor‐free controls. However, tumors did not alter gene expression of Percoll‐enriched microglia isolated from the whole brain. While cognitive, social, and anhedonia‐like behaviors were not altered in tumor‐bearing mice, tumors increased central tendency in the open‐field test; microglia depletion did not reverse this effect. Brain region RT‐qPCR data indicated that microglia depletion attenuated tumor‐induced elevations of neuroinflammatory gene expression in a region‐ and mediator‐specific manner. These results indicate a causal role of microglia in tumor‐induced neuroinflammation. This research advances our understanding of the cellular mechanisms underlying tumor‐induced neuroinflammation in order to understand how brain responses (e.g., behavior) may be altered with subsequent cancer‐related immune challenges.

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A novel targeted approach to delineate a role for estrogen receptor-β in ameliorating murine mammary tumor-associated neuroinflammation

2021

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Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice

Cited by 4 publications

References 53 publications

Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor

Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor

Microglia contribute to mammary tumor‐induced neuroinflammation in a female mouse model

A novel targeted approach to delineate a role for estrogen receptor-β in ameliorating murine mammary tumor-associated neuroinflammation

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