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Investigating Morphological and Cytoskeletal Dynamics of Hippocampal Astrocyte Across Progressive Tauopathy
Investigating Morphological and Cytoskeletal Dynamics of Hippocampal Astrocyte Across Progressive Tauopathy
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103614
- ISBN
- 9798315761525
- DDC
- 616
- 서명/저자
- Investigating Morphological and Cytoskeletal Dynamics of Hippocampal Astrocyte Across Progressive Tauopathy
- 발행사항
- [Sl] : University of California, Los Angeles, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 70 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-11, Section: B.
- 주기사항
- Advisor: Hinman, Jason D.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Los Angeles, 2025.
- 초록/해제
- 요약Astrocytes, an extremely abundant glial cell found throughout the central nervous system, are largely considered to be the primary regulators of brain homeostasis. They fulfill a variety of different functions critical to maintaining a healthy brain, including recycling of neurotransmitters, maintaining the blood brain barrier, and secretion of neurotrophic factors. A key feature of astrocytes that is essential to their myriads of homeostatic functions is their branched cytoskeleton and highly ramified morphology. Their cellular morphology and abundance mean that every cell type within the brain is either contacting or within nanometer proximity to an astrocytic process. Additionally, during brain injury, disease or repair, astrocytes alter their gene transcription, cytoskeleton, and morphology to respond to the noxious stimuli, in a process called activation. Due to their importance in healthy brain function, researchers have expanded their investigations into the role of astrocytes in neurodegenerative disease such as Alzheimer's disease (AD). During the prodromal stage of AD, researchers have found that there are age-associated, region-specific changes in glial-cell gene transcription and activation. Additionally, they observed alterations to the primary component of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP) suggesting that hippocampal astrocytes display disease-associated cytoskeletal atrophy. These cytoskeletal atrophy-associated changes are well-recognized in many amyloid-based mouse models of AD. However, whether this cytoskeletal atrophy translates into alterations of astrocyte morphology, territory occupied by non GFAP filled processes, are only beginning to be conducted. Additionally, research into if a similar phenotype occurs among astrocytes in tau-mediated neurodegeneration remains unexplored. Using an adeno-associated virus to sparsely label the full morphology of hippocampal astrocytes along with confocal microscopy and 3D volumetric reconstruction of individual cells, I aim to investigate in this dissertation if cytoskeletal and morphological alterations occur in hippocampal astrocytes during progressive tauopathy as modeled by the PS19 tau mouse model. In chapter one of this dissertation, I will provide an overview of astrocyte development, form, and function in both healthy and pathological brain states. I will also detail advances in techniques that enable greater visualization of astrocytes ramified morphology. In chapter two, I will detail the observed morphological alterations occurring in the PS19 tau mouse model. Finally in chapter three, I will discuss the impact of my findings within the broader landscape of AD pathology and therapeutics. Early and progression-dependent morphological and cytoskeletal atrophy of astrocytes could drive AD pathology through disruption of astrocyte cell to cell contact, impacting their ability to maintain brain homeostasis. Ultimately, restoring astrocytic form and function in neurodegenerative diseases stands as area ripe for therapeutic development.
- 일반주제명
- Neurosciences
- 일반주제명
- Pathology
- 일반주제명
- Molecular biology
- 일반주제명
- Morphology
- 키워드
- Astrocytes
- 키워드
- Tauopathy
- 기타저자
- University of California, Los Angeles Neuroscience 004F
- 기본자료저록
- Dissertations Abstracts International. 86-11B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798315761525
■035 ▼a(MiAaPQ)AAI32044260
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616
■1001 ▼aMcReynolds, Roy Calvin, III.
■24510▼aInvestigating Morphological and Cytoskeletal Dynamics of Hippocampal Astrocyte Across Progressive Tauopathy
■260 ▼a[Sl]▼bUniversity of California, Los Angeles▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a70 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-11, Section: B.
■500 ▼aAdvisor: Hinman, Jason D.
■5021 ▼aThesis (Ph.D.)--University of California, Los Angeles, 2025.
■520 ▼aAstrocytes, an extremely abundant glial cell found throughout the central nervous system, are largely considered to be the primary regulators of brain homeostasis. They fulfill a variety of different functions critical to maintaining a healthy brain, including recycling of neurotransmitters, maintaining the blood brain barrier, and secretion of neurotrophic factors. A key feature of astrocytes that is essential to their myriads of homeostatic functions is their branched cytoskeleton and highly ramified morphology. Their cellular morphology and abundance mean that every cell type within the brain is either contacting or within nanometer proximity to an astrocytic process. Additionally, during brain injury, disease or repair, astrocytes alter their gene transcription, cytoskeleton, and morphology to respond to the noxious stimuli, in a process called activation. Due to their importance in healthy brain function, researchers have expanded their investigations into the role of astrocytes in neurodegenerative disease such as Alzheimer's disease (AD). During the prodromal stage of AD, researchers have found that there are age-associated, region-specific changes in glial-cell gene transcription and activation. Additionally, they observed alterations to the primary component of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP) suggesting that hippocampal astrocytes display disease-associated cytoskeletal atrophy. These cytoskeletal atrophy-associated changes are well-recognized in many amyloid-based mouse models of AD. However, whether this cytoskeletal atrophy translates into alterations of astrocyte morphology, territory occupied by non GFAP filled processes, are only beginning to be conducted. Additionally, research into if a similar phenotype occurs among astrocytes in tau-mediated neurodegeneration remains unexplored. Using an adeno-associated virus to sparsely label the full morphology of hippocampal astrocytes along with confocal microscopy and 3D volumetric reconstruction of individual cells, I aim to investigate in this dissertation if cytoskeletal and morphological alterations occur in hippocampal astrocytes during progressive tauopathy as modeled by the PS19 tau mouse model. In chapter one of this dissertation, I will provide an overview of astrocyte development, form, and function in both healthy and pathological brain states. I will also detail advances in techniques that enable greater visualization of astrocytes ramified morphology. In chapter two, I will detail the observed morphological alterations occurring in the PS19 tau mouse model. Finally in chapter three, I will discuss the impact of my findings within the broader landscape of AD pathology and therapeutics. Early and progression-dependent morphological and cytoskeletal atrophy of astrocytes could drive AD pathology through disruption of astrocyte cell to cell contact, impacting their ability to maintain brain homeostasis. Ultimately, restoring astrocytic form and function in neurodegenerative diseases stands as area ripe for therapeutic development.
■590 ▼aSchool code: 0031.
■650 4▼aNeurosciences
■650 4▼aPathology
■650 4▼aMolecular biology
■650 4▼aMorphology
■653 ▼aAlzheimer's disease
■653 ▼aAstrocytes
■653 ▼aTauopathy
■653 ▼aCytoskeletal dynamics
■653 ▼aHippocampal astrocyte
■690 ▼a0317
■690 ▼a0307
■690 ▼a0287
■690 ▼a0571
■71020▼aUniversity of California, Los Angeles▼bNeuroscience 004F.
■7730 ▼tDissertations Abstracts International▼g86-11B.
■790 ▼a0031
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357895▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
