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

Neuroinflammation confers changes in brain function (i.e., behavior) that are hypothesized to be adaptive in the short-term, but detrimental (e.g., depression, anxiety) if they persist. Both peripheral tumor growth (outside of the brain) and natural aging independently cause neuroinflammation in rod...

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Main Authors: Ruth M. Barrientos, Lindsay D. Strehle, Ashley A. Lahoud, Leah M. Pyter
Format: Article
Language:English
Published: Elsevier 2020-02-01
Series:Comprehensive Psychoneuroendocrinology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666497620300023
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spelling doaj-24af729053d549ee8e71ff1edb240e012021-05-04T07:33:26ZengElsevierComprehensive Psychoneuroendocrinology2666-49762020-02-011100002Mammary tumors suppress aging-induced neuroinflammation in female Balb/c miceRuth M. Barrientos0Lindsay D. Strehle1Ashley A. Lahoud2Leah M. Pyter3Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA; Department of Neuroscience, Ohio State University, Columbus, OH, USAInstitute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Neuroscience, Ohio State University, Columbus, OH, USAInstitute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, USAInstitute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA; Department of Neuroscience, Ohio State University, Columbus, OH, USA; Corresponding author. Ohio State University, 219 Institute for Behavioral Medicine Research, 460 Medical Center Dr, Columbus, OH, 43210, USA.Neuroinflammation confers changes in brain function (i.e., behavior) that are hypothesized to be adaptive in the short-term, but detrimental (e.g., depression, anxiety) if they persist. Both peripheral tumor growth (outside of the brain) and natural aging independently cause neuroinflammation in rodents, which is corroborated by clinical studies. Mammary tumor effects on neuroinflammation and behavior, however, are typically studied in young rodents, whereas most breast cancer patients are middle-aged. Therefore, the existing literature likely underestimates the resulting neuroinflammation that may occur in clinical cancer populations. The present study tested the hypothesis that aging exacerbates mammary tumor-induced neuroinflammation in female mice. Aging (16 months and ovariectomized) increased body and spleen masses, whereas tumors grew faster and increased spleen mass in young mice (12 weeks) only. Tumors (IL-6, IL-10, TNFα, MCP-1, CXCL1, IP-10) and aging (IL-10, IFNγ) independently increased circulating inflammatory markers, although these variables were only significantly additive in one case (TNFα). In contrast to our prediction, the interaction between tumors and aging resulted in reduced mRNA and protein expression of select inflammatory markers in the hippocampus of tumor-bearing aged mice relative to aged controls. These results indicate that tumors reduce inflammatory activation in the brains of aged mice, a deficit that is likely disadvantageous. Further understanding of how aging and cancer interact to affect brain function is necessary to provide clinically-relevant results and identify mechanisms underlying persistent behavioral issues hampering adult cancer patients.http://www.sciencedirect.com/science/article/pii/S2666497620300023CytokinesChemokinesHippocampusCancer
collection DOAJ
language English
format Article
sources DOAJ
author Ruth M. Barrientos
Lindsay D. Strehle
Ashley A. Lahoud
Leah M. Pyter
spellingShingle Ruth M. Barrientos
Lindsay D. Strehle
Ashley A. Lahoud
Leah M. Pyter
Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice
Comprehensive Psychoneuroendocrinology
Cytokines
Chemokines
Hippocampus
Cancer
author_facet Ruth M. Barrientos
Lindsay D. Strehle
Ashley A. Lahoud
Leah M. Pyter
author_sort Ruth M. Barrientos
title Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice
title_short Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice
title_full Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice
title_fullStr Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice
title_full_unstemmed Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice
title_sort mammary tumors suppress aging-induced neuroinflammation in female balb/c mice
publisher Elsevier
series Comprehensive Psychoneuroendocrinology
issn 2666-4976
publishDate 2020-02-01
description Neuroinflammation confers changes in brain function (i.e., behavior) that are hypothesized to be adaptive in the short-term, but detrimental (e.g., depression, anxiety) if they persist. Both peripheral tumor growth (outside of the brain) and natural aging independently cause neuroinflammation in rodents, which is corroborated by clinical studies. Mammary tumor effects on neuroinflammation and behavior, however, are typically studied in young rodents, whereas most breast cancer patients are middle-aged. Therefore, the existing literature likely underestimates the resulting neuroinflammation that may occur in clinical cancer populations. The present study tested the hypothesis that aging exacerbates mammary tumor-induced neuroinflammation in female mice. Aging (16 months and ovariectomized) increased body and spleen masses, whereas tumors grew faster and increased spleen mass in young mice (12 weeks) only. Tumors (IL-6, IL-10, TNFα, MCP-1, CXCL1, IP-10) and aging (IL-10, IFNγ) independently increased circulating inflammatory markers, although these variables were only significantly additive in one case (TNFα). In contrast to our prediction, the interaction between tumors and aging resulted in reduced mRNA and protein expression of select inflammatory markers in the hippocampus of tumor-bearing aged mice relative to aged controls. These results indicate that tumors reduce inflammatory activation in the brains of aged mice, a deficit that is likely disadvantageous. Further understanding of how aging and cancer interact to affect brain function is necessary to provide clinically-relevant results and identify mechanisms underlying persistent behavioral issues hampering adult cancer patients.
topic Cytokines
Chemokines
Hippocampus
Cancer
url http://www.sciencedirect.com/science/article/pii/S2666497620300023
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