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Sphingolipid Control of Neural Circuits Via Glial Catabolism
Sphingolipid Control of Neural Circuits Via Glial Catabolism
Sphingolipid Control of Neural Circuits Via Glial Catabolism

Detailed Information

Material Type  
 단행본
 
0017164289
Date and Time of Latest Transaction  
20250211152943
ISBN  
9798342136297
DDC  
500
Author  
Vaughen, John Philip.
Title/Author  
Sphingolipid Control of Neural Circuits Via Glial Catabolism
Publish Info  
[Sl] : Stanford University, 2024
Publish Info  
Ann Arbor : ProQuest Dissertations & Theses, 2024
Material Info  
119 p
General Note  
Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
General Note  
Advisor: Clandinin, Thomas R.
학위논문주기  
Thesis (Ph.D.)--Stanford University, 2024.
Abstracts/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  
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MARC

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■006m          o    d                
■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.

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