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Sphingolipid Control of Neural Circuits Via Glial Catabolism.
Sphingolipid Control of Neural Circuits Via Glial Catabolism.
- 자료유형
- 학위논문
- Control Number
- 0017164289
- International Standard Book Number
- 9798342136297
- Dewey Decimal Classification Number
- 500
- Main Entry-Personal Name
- Vaughen, John Philip.
- Publication, Distribution, etc. (Imprint
- [S.l.] : Stanford University., 2024
- Publication, Distribution, etc. (Imprint
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- Physical Description
- 119 p.
- General Note
- Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
- General Note
- Advisor: Clandinin, Thomas R.
- Dissertation Note
- Thesis (Ph.D.)--Stanford University, 2024.
- Summary, Etc.
- 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.
- Subject Added Entry-Topical Term
- Neurodegeneration.
- Subject Added Entry-Topical Term
- Membranes.
- Subject Added Entry-Topical Term
- Behavior.
- Subject Added Entry-Topical Term
- Neurons.
- Subject Added Entry-Topical Term
- Homeostasis.
- Subject Added Entry-Topical Term
- CRISPR.
- Subject Added Entry-Topical Term
- Alzheimer's disease.
- Subject Added Entry-Topical Term
- Blood-brain barrier.
- Subject Added Entry-Topical Term
- Hydrocarbons.
- Subject Added Entry-Topical Term
- Regulation.
- Subject Added Entry-Topical Term
- Pacemakers.
- Subject Added Entry-Topical Term
- Disease.
- Subject Added Entry-Topical Term
- Biosynthesis.
- Subject Added Entry-Topical Term
- Mutation.
- Subject Added Entry-Topical Term
- Carbon.
- Subject Added Entry-Topical Term
- Cholesterol.
- Subject Added Entry-Topical Term
- Brain.
- Subject Added Entry-Topical Term
- Insects.
- Subject Added Entry-Topical Term
- Metabolism.
- Subject Added Entry-Topical Term
- Circadian rhythm.
- Subject Added Entry-Topical Term
- Lipids.
- Subject Added Entry-Topical Term
- Bioengineering.
- Subject Added Entry-Topical Term
- Bioinformatics.
- Subject Added Entry-Topical Term
- Neurosciences.
- Subject Added Entry-Topical Term
- Physiology.
- Added Entry-Corporate Name
- Stanford University.
- Host Item Entry
- Dissertations Abstracts International. 86-04B.
- Electronic Location and Access
- 로그인을 한후 보실 수 있는 자료입니다.
- Control Number
- joongbu:657668