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Gene Expression, Regulation, and Implication in the Rat Models of Opioid Use Disorder
Gene Expression, Regulation, and Implication in the Rat Models of Opioid Use Disorder
Gene Expression, Regulation, and Implication in the Rat Models of Opioid Use Disorder

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202103539
ISBN  
9798290912530
DDC  
150
저자명  
Liu, Shirelle Xinyue.
서명/저자  
Gene Expression, Regulation, and Implication in the Rat Models of Opioid Use Disorder
발행사항  
[Sl] : University of Minnesota, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
199 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-01, Section: B.
주기사항  
Advisor: Gewirtz, Jonathan C.;Tran, Phu V.
학위논문주기  
Thesis (Ph.D.)--University of Minnesota, 2025.
초록/해제  
요약Substance use disorders (SUDs), including opioid use disorder (OUD), remain a major global health problem with substantial individual differences in vulnerability. Given the chronic nature of SUDs and the long-term impact of early-life experiences (e.g., childhood trauma) on addiction vulnerability in adulthood, changes in SUD vulnerability likely involve long-term epigenetic dysregulation. However, molecular mechanisms in the brain underlying individual differences in SUD vulnerability remain unclear. The goal of this dissertation was to evaluate how early-life experiences affect epigenetic regulation into adulthood using a prenatal-neonatal iron deficiency and choline supplementation rat model, and to characterize transcriptional and epigenetic signatures associated with morphine exposure and individual differences in OUD vulnerability in rat models capturing 3 distinct stages of human OUD. Study 1 showed that early-life ID and choline supplementation interacted to epigenetically regulate the expression of genes encoding JmjC-ARID domain-containing protein 1B and brain-derived neurotrophic factor, a potential biomarker for heroin use, in the rat hippocampus into adulthood. Study 2 showed that repeated exposure to the opioid morphine activated synaptogenesis and other neuroplasticity-related gene networks in the dorsomedial prefrontal cortex of rats. Study 3 showed that differential gene expression and chromatin accessibility in the medial prefrontal cortex were associated with individual differences in rat behavioral models of OUD. Overall, these studies emphasized the significant long-term effects of environmentally induced epigenetic dysregulation and extended the understanding of brain molecular mechanisms underlying individual differences in OUD vulnerability in rat models.
일반주제명  
Behavioral sciences
일반주제명  
Psychobiology
일반주제명  
Molecular biology
일반주제명  
Genetics
키워드  
Substance use disorders
키워드  
Opioid use disorder
키워드  
Gene expression
키워드  
Molecular mechanisms
기타저자  
University of Minnesota Psychology
기본자료저록  
Dissertations Abstracts International. 87-01B.
전자적 위치 및 접속  
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■035    ▼a(MiAaPQ)AAI32040791
■040    ▼aMiAaPQ▼cMiAaPQ
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■1001  ▼aLiu,  Shirelle  Xinyue.
■24510▼aGene  Expression,  Regulation,  and  Implication  in  the  Rat  Models  of  Opioid  Use  Disorder
■260    ▼a[Sl]▼bUniversity  of  Minnesota▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a199  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-01,  Section:  B.
■500    ▼aAdvisor:  Gewirtz,  Jonathan  C.;Tran,  Phu  V.
■5021  ▼aThesis  (Ph.D.)--University  of  Minnesota,  2025.
■520    ▼aSubstance  use  disorders  (SUDs),  including  opioid  use  disorder  (OUD),  remain  a  major  global  health  problem  with  substantial  individual  differences  in  vulnerability.  Given  the  chronic  nature  of  SUDs  and  the  long-term  impact  of  early-life  experiences  (e.g.,  childhood  trauma)  on  addiction  vulnerability  in  adulthood,  changes  in  SUD  vulnerability  likely  involve  long-term  epigenetic  dysregulation.  However,  molecular  mechanisms  in  the  brain  underlying  individual  differences  in  SUD  vulnerability  remain  unclear.  The  goal  of  this  dissertation  was  to  evaluate  how  early-life  experiences  affect  epigenetic  regulation  into  adulthood  using  a  prenatal-neonatal  iron  deficiency  and  choline  supplementation  rat  model,  and  to  characterize  transcriptional  and  epigenetic  signatures  associated  with  morphine  exposure  and  individual  differences  in  OUD  vulnerability  in  rat  models  capturing  3  distinct  stages  of  human  OUD.  Study  1  showed  that  early-life  ID  and  choline  supplementation  interacted  to  epigenetically  regulate  the  expression  of  genes  encoding  JmjC-ARID  domain-containing  protein  1B  and  brain-derived  neurotrophic  factor,  a  potential  biomarker  for  heroin  use,  in  the  rat  hippocampus  into  adulthood.  Study  2  showed  that  repeated  exposure  to  the  opioid  morphine  activated  synaptogenesis  and  other  neuroplasticity-related  gene  networks  in  the  dorsomedial  prefrontal  cortex  of  rats.  Study  3  showed  that  differential  gene  expression  and  chromatin  accessibility  in  the  medial  prefrontal  cortex  were  associated  with  individual  differences  in  rat  behavioral  models  of  OUD.  Overall,  these  studies  emphasized  the  significant  long-term  effects  of  environmentally  induced  epigenetic  dysregulation  and  extended  the  understanding  of  brain  molecular  mechanisms  underlying  individual  differences  in  OUD  vulnerability  in  rat  models.
■590    ▼aSchool  code:  0130.
■650  4▼aBehavioral  sciences
■650  4▼aPsychobiology
■650  4▼aMolecular  biology
■650  4▼aGenetics
■653    ▼aSubstance  use  disorders
■653    ▼aOpioid  use  disorder
■653    ▼aGene  expression
■653    ▼aMolecular  mechanisms
■690    ▼a0602
■690    ▼a0349
■690    ▼a0369
■690    ▼a0307
■71020▼aUniversity  of  Minnesota▼bPsychology.
■7730  ▼tDissertations  Abstracts  International▼g87-01B.
■790    ▼a0130
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357634▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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