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Sphingolipid Control of Neural Circuits Via Glial Catabolism
Sphingolipid Control of Neural Circuits Via Glial Catabolism
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152943
- ISBN
- 9798342136297
- DDC
- 500
- 서명/저자
- Sphingolipid Control of Neural Circuits Via Glial Catabolism
- 발행사항
- [Sl] : Stanford University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 119 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
- 주기사항
- Advisor: Clandinin, Thomas R.
- 학위논문주기
- Thesis (Ph.D.)--Stanford University, 2024.
- 초록/해제
- 요약Sphingolipids are critical amphipathic molecules present in all eukaryotic cell membranes that are enriched in the developing and adult brain. Though strongly implicated in most neurological diseases, how sphingolipids function in and between brain cells in vivo remains largely enigmatic. Here we dissect the brain functions of Glucocerebrosidase (GBA), a conserved lysosomal hydrolase for sphingolipid catabolism, in a Drosophila model. We identify that glia produce GBA for sphingolipid degradation and neural lysosomal function, and demonstrate that glial gba1bknockout causes diurnal protein aggregate formation, sleep loss, and impaired neurite remodeling in a dynamic circadian circuit that grows and shrinks each day. Remarkably, lipidomics targeted across both time and age revealed diurnal fluctuations in sphingolipids during adulthood as well as a unique sphingolipidome during brain development. The developmental sphingolipidome is characterized by glial catabolism and coordinated neural biosynthesis, and developmental sphingolipids dominate adult patterns of substrate accumulation in glial catabolic mutants. The striking compartmentalization of sphingolipid metabolism between glia and neurons likely acts to finetune neuronal structure and function during both development, adult remodeling, and disease.
- 일반주제명
- Neurodegeneration
- 일반주제명
- Membranes
- 일반주제명
- Behavior
- 일반주제명
- Neurons
- 일반주제명
- Homeostasis
- 일반주제명
- CRISPR
- 일반주제명
- Alzheimer's disease
- 일반주제명
- Blood-brain barrier
- 일반주제명
- Hydrocarbons
- 일반주제명
- Regulation
- 일반주제명
- Pacemakers
- 일반주제명
- Disease
- 일반주제명
- Biosynthesis
- 일반주제명
- Mutation
- 일반주제명
- Carbon
- 일반주제명
- Cholesterol
- 일반주제명
- Brain
- 일반주제명
- Insects
- 일반주제명
- Metabolism
- 일반주제명
- Circadian rhythm
- 일반주제명
- Lipids
- 일반주제명
- Bioengineering
- 일반주제명
- Bioinformatics
- 일반주제명
- Neurosciences
- 일반주제명
- Physiology
- 기타저자
- Stanford University.
- 기본자료저록
- Dissertations Abstracts International. 86-04B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■007cr#unu||||||||
■020 ▼a9798342136297
■035 ▼a(MiAaPQ)AAI31591793
■035 ▼a(MiAaPQ)Stanfordwn900ms6337
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a500
■1001 ▼aVaughen, John Philip.
■24510▼aSphingolipid Control of Neural Circuits Via Glial Catabolism
■260 ▼a[Sl]▼bStanford University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a119 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-04, Section: B.
■500 ▼aAdvisor: Clandinin, Thomas R.
■5021 ▼aThesis (Ph.D.)--Stanford University, 2024.
■520 ▼aSphingolipids are critical amphipathic molecules present in all eukaryotic cell membranes that are enriched in the developing and adult brain. Though strongly implicated in most neurological diseases, how sphingolipids function in and between brain cells in vivo remains largely enigmatic. Here we dissect the brain functions of Glucocerebrosidase (GBA), a conserved lysosomal hydrolase for sphingolipid catabolism, in a Drosophila model. We identify that glia produce GBA for sphingolipid degradation and neural lysosomal function, and demonstrate that glial gba1bknockout causes diurnal protein aggregate formation, sleep loss, and impaired neurite remodeling in a dynamic circadian circuit that grows and shrinks each day. Remarkably, lipidomics targeted across both time and age revealed diurnal fluctuations in sphingolipids during adulthood as well as a unique sphingolipidome during brain development. The developmental sphingolipidome is characterized by glial catabolism and coordinated neural biosynthesis, and developmental sphingolipids dominate adult patterns of substrate accumulation in glial catabolic mutants. The striking compartmentalization of sphingolipid metabolism between glia and neurons likely acts to finetune neuronal structure and function during both development, adult remodeling, and disease.
■590 ▼aSchool code: 0212.
■650 4▼aNeurodegeneration
■650 4▼aMembranes
■650 4▼aBehavior
■650 4▼aNeurons
■650 4▼aHomeostasis
■650 4▼aCRISPR
■650 4▼aAlzheimer's disease
■650 4▼aBlood-brain barrier
■650 4▼aHydrocarbons
■650 4▼aRegulation
■650 4▼aPacemakers
■650 4▼aDisease
■650 4▼aBiosynthesis
■650 4▼aMutation
■650 4▼aCarbon
■650 4▼aCholesterol
■650 4▼aBrain
■650 4▼aInsects
■650 4▼aMetabolism
■650 4▼aCircadian rhythm
■650 4▼aLipids
■650 4▼aBioengineering
■650 4▼aBioinformatics
■650 4▼aNeurosciences
■650 4▼aPhysiology
■690 ▼a0202
■690 ▼a0715
■690 ▼a0317
■690 ▼a0719
■71020▼aStanford University.
■7730 ▼tDissertations Abstracts International▼g86-04B.
■790 ▼a0212
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164289▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.


