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Neurobiological Mechanisms of Mammary Tumor-Induced Neuroinflammation in a Female Mouse Model
Neurobiological Mechanisms of Mammary Tumor-Induced Neuroinflammation in a Female Mouse Model
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105707
- ISBN
- 9798270221553
- DDC
- 616
- 서명/저자
- Neurobiological Mechanisms of Mammary Tumor-Induced Neuroinflammation in a Female Mouse Model
- 발행사항
- [Sl] : The Ohio State University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 189 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
- 주기사항
- Advisor: Pyter, Leah.
- 학위논문주기
- Thesis (Ph.D.)--The Ohio State University, 2024.
- 초록/해제
- 요약Patients with breast cancer experience debilitating behavioral side effects and exhibit elevated concentrations of circulating inflammatory mediators, even prior to treatment. Inflammation is a proposed mechanism underlying the etiology of cognitive and mood disturbances and thus may be contributing to tumor-induced behavioral side effects. Preclinical rodent models likewise display impairments in learning/memory and anxiety-and depressive-like behaviors. In addition to tumor-induced elevations of circulating inflammatory mediators, tumor-bearing rodent models display neuroinflammation in brain regions important in regulating behavior. However, the cellular and molecular mechanisms by which tumor-induced behavioral side effects occur remain unknown. Estrogen is not only implicated in the etiology of breast cancer, but also in regulating inflammation and behavior; therefore, estrogen signaling may mediate the relationships between tumor-induced neuroinflammation and behavioral side effects. Here, I examine the extent to which 1. estrogen modulates tumor-induced neuroinflammatory and behavioral outcomes and 2. different cells in the brain (i.e., microglia and endothelial cells) contribute to the observed tumor-induced neuroinflammatory phenotype using orthotopic and syngeneic mammary tumors in female mice. In Chapter 2, I demonstrate that ovarian status modulates tumor-induced endocrine and neuroinflammatory outcomes. Most notably, I show that a mammary tumor in ovary-intact mice reduces circulating estradiol and alters estrogen-related signaling in the brain. Further, tumors in ovariectomized mice increase circulating estradiol and modestly exacerbate tumor-induced peripheral and central inflammation. Next, in Chapter 3 I demonstrate that brain-specific estradiol supplementation attenuates tumor-induced fatigue in group-housed mice, but not singly housed mice; the attenuation of tumor-induced fatigue in group-housed mice is not mediated by neuroinflammatory mediators. In Chapter 4, I demonstrate that a mammary tumor increases the reactivity of microglia and astrocytes in the hippocampus and amygdala using immunofluorescent analyses. Moreover, I identify a causal role of microglia in tumor-induced amygdalar inflammation. Finally, in Chapter 5, I demonstrate that a mammary tumor increases inflammatory transcriptional, protein, and functional changes in brain endothelial cells. Identifying tumor-induced endocrine and neurobiological alterations can inform how brain responses may be altered with subsequent cancer-related immune challenges and inform targeted, individualized interventions to ameliorate the debilitating behavioral side effects.
- 일반주제명
- Neurosciences
- 일반주제명
- Neurobiology
- 일반주제명
- Cellular biology
- 일반주제명
- Oncology
- 키워드
- Cancer
- 키워드
- Brain
- 키워드
- Inflammation
- 키워드
- Microglia
- 키워드
- Astrocytes
- 기타저자
- The Ohio State University Neuroscience Graduate Studies Program
- 기본자료저록
- Dissertations Abstracts International. 87-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616
■1001 ▼aStrehle, Lindsay Danielle.
■24510▼aNeurobiological Mechanisms of Mammary Tumor-Induced Neuroinflammation in a Female Mouse Model
■260 ▼a[Sl]▼bThe Ohio State University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a189 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-06, Section: B.
■500 ▼aAdvisor: Pyter, Leah.
■5021 ▼aThesis (Ph.D.)--The Ohio State University, 2024.
■520 ▼aPatients with breast cancer experience debilitating behavioral side effects and exhibit elevated concentrations of circulating inflammatory mediators, even prior to treatment. Inflammation is a proposed mechanism underlying the etiology of cognitive and mood disturbances and thus may be contributing to tumor-induced behavioral side effects. Preclinical rodent models likewise display impairments in learning/memory and anxiety-and depressive-like behaviors. In addition to tumor-induced elevations of circulating inflammatory mediators, tumor-bearing rodent models display neuroinflammation in brain regions important in regulating behavior. However, the cellular and molecular mechanisms by which tumor-induced behavioral side effects occur remain unknown. Estrogen is not only implicated in the etiology of breast cancer, but also in regulating inflammation and behavior; therefore, estrogen signaling may mediate the relationships between tumor-induced neuroinflammation and behavioral side effects. Here, I examine the extent to which 1. estrogen modulates tumor-induced neuroinflammatory and behavioral outcomes and 2. different cells in the brain (i.e., microglia and endothelial cells) contribute to the observed tumor-induced neuroinflammatory phenotype using orthotopic and syngeneic mammary tumors in female mice. In Chapter 2, I demonstrate that ovarian status modulates tumor-induced endocrine and neuroinflammatory outcomes. Most notably, I show that a mammary tumor in ovary-intact mice reduces circulating estradiol and alters estrogen-related signaling in the brain. Further, tumors in ovariectomized mice increase circulating estradiol and modestly exacerbate tumor-induced peripheral and central inflammation. Next, in Chapter 3 I demonstrate that brain-specific estradiol supplementation attenuates tumor-induced fatigue in group-housed mice, but not singly housed mice; the attenuation of tumor-induced fatigue in group-housed mice is not mediated by neuroinflammatory mediators. In Chapter 4, I demonstrate that a mammary tumor increases the reactivity of microglia and astrocytes in the hippocampus and amygdala using immunofluorescent analyses. Moreover, I identify a causal role of microglia in tumor-induced amygdalar inflammation. Finally, in Chapter 5, I demonstrate that a mammary tumor increases inflammatory transcriptional, protein, and functional changes in brain endothelial cells. Identifying tumor-induced endocrine and neurobiological alterations can inform how brain responses may be altered with subsequent cancer-related immune challenges and inform targeted, individualized interventions to ameliorate the debilitating behavioral side effects.
■590 ▼aSchool code: 0168.
■650 4▼aNeurosciences
■650 4▼aNeurobiology
■650 4▼aCellular biology
■650 4▼aOncology
■653 ▼aCancer
■653 ▼aBrain
■653 ▼aInflammation
■653 ▼aMicroglia
■653 ▼aBrain endothelial cells
■653 ▼aAstrocytes
■690 ▼a0317
■690 ▼a0379
■690 ▼a0992
■71020▼aThe Ohio State University▼bNeuroscience Graduate Studies Program.
■7730 ▼tDissertations Abstracts International▼g87-06B.
■790 ▼a0168
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17361110▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
