Cancer treatment induces neuroinflammation and behavioral deficits in mice
Introduction: Cancer survivors are increasingly diagnosed with a syndrome of neurocognitive dysfunction termed cancer-related cognitive impairment (CRCI). Chemotherapy and radiation therapy have been implicated in CRCI; however, its underlying pathogenesis remains unclear, hindering effective preven...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2022.1067298/full |
| _version_ | 1797956941955203072 |
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| author | Kimberly Demos-Davies Jessica Lawrence Jessica Lawrence Allison Rogich Erin Lind Davis Seelig Davis Seelig |
| author_facet | Kimberly Demos-Davies Jessica Lawrence Jessica Lawrence Allison Rogich Erin Lind Davis Seelig Davis Seelig |
| author_sort | Kimberly Demos-Davies |
| collection | DOAJ |
| description | Introduction: Cancer survivors are increasingly diagnosed with a syndrome of neurocognitive dysfunction termed cancer-related cognitive impairment (CRCI). Chemotherapy and radiation therapy have been implicated in CRCI; however, its underlying pathogenesis remains unclear, hindering effective prevention or treatment.Methods: We used the hairless strain SKH1 (11–12-week-old) and treated the mice with radiation to the right hindlimb, doxorubicin (a chemotherapy agent), concurrent radiation, and doxorubicin, or no treatment (control). Neurocognition was evaluated via standardized behavioral testing following treatment. Mice were subsequently humanely euthanized, and plasma and brains were collected to identify inflammatory changes.Results: Mice treated with radiation, doxorubicin, or both radiation and doxorubicin demonstrated equivalent hippocampal dependent memory deficits and significant increases in activated microglia and astrocytes compared to control mice. Doxorubicin-treated mice had significantly increased plasma IL-6 and failed to gain weight compared to control mice over the study period.Discussion: This study demonstrates that non-brain directed radiation induces both gliosis and neurocognitive deficits. Moreover, this work presents the first characterization of SKH1 mice as a relevant and facile animal model of CRCI. This study provides a platform from which to build further studies to identify potential key targets that contribute to CRCI such that strategies can be developed to mitigate unintended neuropathologic consequences associated with anticancer treatment. |
| first_indexed | 2024-04-10T23:56:34Z |
| format | Article |
| id | doaj.art-43ad44cc99904a32951da5d1b6649a1e |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-10T23:56:34Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-43ad44cc99904a32951da5d1b6649a1e2023-01-10T12:14:27ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532023-01-011610.3389/fnbeh.2022.10672981067298Cancer treatment induces neuroinflammation and behavioral deficits in miceKimberly Demos-Davies0Jessica Lawrence1Jessica Lawrence2Allison Rogich3Erin Lind4Davis Seelig5Davis Seelig6Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, Saint Paul, MN, United StatesDepartment of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, Saint Paul, MN, United StatesMasonic Cancer Center, University of Minnesota, Minneapolis, MN, United StatesDepartment of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, Saint Paul, MN, United StatesDepartment of Neuroscience, University of Minnesota, Minneapolis, MN, United StatesDepartment of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, Saint Paul, MN, United StatesMasonic Cancer Center, University of Minnesota, Minneapolis, MN, United StatesIntroduction: Cancer survivors are increasingly diagnosed with a syndrome of neurocognitive dysfunction termed cancer-related cognitive impairment (CRCI). Chemotherapy and radiation therapy have been implicated in CRCI; however, its underlying pathogenesis remains unclear, hindering effective prevention or treatment.Methods: We used the hairless strain SKH1 (11–12-week-old) and treated the mice with radiation to the right hindlimb, doxorubicin (a chemotherapy agent), concurrent radiation, and doxorubicin, or no treatment (control). Neurocognition was evaluated via standardized behavioral testing following treatment. Mice were subsequently humanely euthanized, and plasma and brains were collected to identify inflammatory changes.Results: Mice treated with radiation, doxorubicin, or both radiation and doxorubicin demonstrated equivalent hippocampal dependent memory deficits and significant increases in activated microglia and astrocytes compared to control mice. Doxorubicin-treated mice had significantly increased plasma IL-6 and failed to gain weight compared to control mice over the study period.Discussion: This study demonstrates that non-brain directed radiation induces both gliosis and neurocognitive deficits. Moreover, this work presents the first characterization of SKH1 mice as a relevant and facile animal model of CRCI. This study provides a platform from which to build further studies to identify potential key targets that contribute to CRCI such that strategies can be developed to mitigate unintended neuropathologic consequences associated with anticancer treatment.https://www.frontiersin.org/articles/10.3389/fnbeh.2022.1067298/fullcancer treatmentneuroinflammationneurobehaviorcancer-related cognitive impairmentSKH1 mice |
| spellingShingle | Kimberly Demos-Davies Jessica Lawrence Jessica Lawrence Allison Rogich Erin Lind Davis Seelig Davis Seelig Cancer treatment induces neuroinflammation and behavioral deficits in mice Frontiers in Behavioral Neuroscience cancer treatment neuroinflammation neurobehavior cancer-related cognitive impairment SKH1 mice |
| title | Cancer treatment induces neuroinflammation and behavioral deficits in mice |
| title_full | Cancer treatment induces neuroinflammation and behavioral deficits in mice |
| title_fullStr | Cancer treatment induces neuroinflammation and behavioral deficits in mice |
| title_full_unstemmed | Cancer treatment induces neuroinflammation and behavioral deficits in mice |
| title_short | Cancer treatment induces neuroinflammation and behavioral deficits in mice |
| title_sort | cancer treatment induces neuroinflammation and behavioral deficits in mice |
| topic | cancer treatment neuroinflammation neurobehavior cancer-related cognitive impairment SKH1 mice |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2022.1067298/full |
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