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Effects of Lateralized Hippocampal Damage and Pituitary Gonadotrope Dysfunction in a Mouse Model of Temporal Lobe Epilepsy
Effects of Lateralized Hippocampal Damage and Pituitary Gonadotrope Dysfunction in a Mouse...
Effects of Lateralized Hippocampal Damage and Pituitary Gonadotrope Dysfunction in a Mouse Model of Temporal Lobe Epilepsy

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202105245
ISBN  
9798291572818
DDC  
616
저자명  
Cutia, Cathryn A.
서명/저자  
Effects of Lateralized Hippocampal Damage and Pituitary Gonadotrope Dysfunction in a Mouse Model of Temporal Lobe Epilepsy
발행사항  
[Sl] : University of Illinois at Urbana-Champaign, 2023
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2023
형태사항  
172 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
주기사항  
Advisor: Christian-Hinman, Catherine.
학위논문주기  
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2023.
초록/해제  
요약Reproductive endocrine dysfunction is a common comorbidity of temporal lobe epilepsy (TLE). The specific mechanisms that link temporal lobe seizures to reproductive endocrine dysfunction remain unknown. However, clinical reports suggest that epilepsy-associated hypothalamic-pituitary-gonadal (HPG) axis dysfunction likely underlies the development of reproductive endocrine disorders. The intrahippocampal kainic acid (IHKA) mouse model of TLE also shows reproductive endocrine dysfunction as a majority of female IHKA treated animals display estrous cycle disruption. Furthermore, IHKA mice display alterations in the HPG axis as the activity of, and input to, hypothalamic gonadotropin-releasing hormone (GnRH) neurons is changed in IHKA females that develop estrous cycle elongation. However, further work in this model is needed to identify a specific mechanism that links the epilepsy-associated changes in hypothalamic circuitry to the development of reproductive endocrine dysfunction. The overall goal of this dissertation is to evaluate the progression and robustness of the reproductive endocrine dysfunction phenotype in female IHKA mice and to determine if epilepsy-associated hypothalamic changes in this model impact the pituitary. Chapter 2 investigates the differences in the presentation and progression of pituitary and gonadal phenotypic outcomes in female mice injected in the left vs. right dorsal hippocampus with KA. Chapter 3 continues to investigate the impacts of IHKA injection site by characterizing seizure burden differences in the left vs. right IHKA mice. Chapter 4 investigates the epilepsy-associated changes in pituitary release of gonadotropins and sensitivity to GnRH. The results from Chapter 2 and 3 indicate that the side of IHKA injection does not impact the development of comorbid estrous cycle disruption in females, but that KA injection site can impact pituitary gene expression and seizure burden in a sex- and estrous cycle-dependent manner. The results from Chapter 4 indicate that there are epilepsy-associated elevations in pituitary sensitivity to GnRH on certain estrous cycle stages in the absence of changes to the pattern of gonadotropin release. Overall, the data in this dissertation demonstrate that, within the IHKA model, lateralization of hippocampal damage can have implications on phenotypes present, and that temporal lobe seizures lead to altered pituitary function. This data demonstrates the usefulness of the IHKA model in the study of mechanisms linking temporal lobe seizures to altered reproductive endocrine function and vice versa.
일반주제명  
Neurosciences
일반주제명  
Physiology
일반주제명  
Health sciences
일반주제명  
Endocrinology
키워드  
Reproductive endocrine dysfunction
키워드  
Mouse model
키워드  
Temporal lobe epilepsy
키워드  
Intrahippocampal kainic acid
키워드  
Gonadotropin-releasing hormone
기타저자  
University of Illinois at Urbana-Champaign Neuroscience Program
기본자료저록  
Dissertations Abstracts International. 87-03B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aCutia,  Cathryn  A.
■24510▼aEffects  of  Lateralized  Hippocampal  Damage  and  Pituitary  Gonadotrope  Dysfunction  in  a  Mouse  Model  of  Temporal  Lobe  Epilepsy
■260    ▼a[Sl]▼bUniversity  of  Illinois  at  Urbana-Champaign▼c2023
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2023
■300    ▼a172  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-03,  Section:  B.
■500    ▼aAdvisor:  Christian-Hinman,  Catherine.
■5021  ▼aThesis  (Ph.D.)--University  of  Illinois  at  Urbana-Champaign,  2023.
■520    ▼aReproductive  endocrine  dysfunction  is  a  common  comorbidity  of  temporal  lobe  epilepsy  (TLE).  The  specific  mechanisms  that  link  temporal  lobe  seizures  to  reproductive  endocrine  dysfunction  remain  unknown.  However,  clinical  reports  suggest  that  epilepsy-associated  hypothalamic-pituitary-gonadal  (HPG)  axis  dysfunction  likely  underlies  the  development  of  reproductive  endocrine  disorders.  The  intrahippocampal  kainic  acid  (IHKA)  mouse  model  of  TLE  also  shows  reproductive  endocrine  dysfunction  as  a  majority  of  female  IHKA  treated  animals  display  estrous  cycle  disruption.  Furthermore,  IHKA  mice  display  alterations  in  the  HPG  axis  as  the  activity  of,  and  input  to,  hypothalamic  gonadotropin-releasing  hormone  (GnRH)  neurons  is  changed  in  IHKA  females  that  develop  estrous  cycle  elongation.  However,  further  work  in  this  model  is  needed  to  identify  a  specific  mechanism  that  links  the  epilepsy-associated  changes  in  hypothalamic  circuitry  to  the  development  of  reproductive  endocrine  dysfunction.  The  overall  goal  of  this  dissertation  is  to  evaluate  the  progression  and  robustness  of  the  reproductive  endocrine  dysfunction  phenotype  in  female  IHKA  mice  and  to  determine  if  epilepsy-associated  hypothalamic  changes  in  this  model  impact  the  pituitary.  Chapter  2  investigates  the  differences  in  the  presentation  and  progression  of  pituitary  and  gonadal  phenotypic  outcomes  in  female  mice  injected  in  the  left  vs.  right  dorsal  hippocampus  with  KA.  Chapter  3  continues  to  investigate  the  impacts  of  IHKA  injection  site  by  characterizing  seizure  burden  differences  in  the  left  vs.  right  IHKA  mice.  Chapter  4  investigates  the  epilepsy-associated  changes  in  pituitary  release  of  gonadotropins  and  sensitivity  to  GnRH.  The  results  from  Chapter  2  and  3  indicate  that  the  side  of  IHKA  injection  does  not  impact  the  development  of  comorbid  estrous  cycle  disruption  in  females,  but  that  KA  injection  site  can  impact  pituitary  gene  expression  and  seizure  burden  in  a  sex-  and  estrous  cycle-dependent  manner.  The  results  from  Chapter  4  indicate  that  there  are  epilepsy-associated  elevations  in  pituitary  sensitivity  to  GnRH  on  certain  estrous  cycle  stages  in  the  absence  of  changes  to  the  pattern  of  gonadotropin  release.  Overall,  the  data  in  this  dissertation  demonstrate  that,  within  the  IHKA  model,  lateralization  of  hippocampal  damage  can  have  implications  on  phenotypes  present,  and  that  temporal  lobe  seizures  lead  to  altered  pituitary  function.  This  data  demonstrates  the  usefulness  of  the  IHKA  model  in  the  study  of  mechanisms  linking  temporal  lobe  seizures  to  altered  reproductive  endocrine  function  and  vice  versa.
■590    ▼aSchool  code:  0090.
■650  4▼aNeurosciences
■650  4▼aPhysiology
■650  4▼aHealth  sciences
■650  4▼aEndocrinology
■653    ▼aReproductive  endocrine  dysfunction
■653    ▼aMouse  model
■653    ▼aTemporal  lobe  epilepsy
■653    ▼aIntrahippocampal  kainic  acid
■653    ▼aGonadotropin-releasing  hormone
■690    ▼a0317
■690    ▼a0566
■690    ▼a0409
■690    ▼a0719
■71020▼aUniversity  of  Illinois  at  Urbana-Champaign▼bNeuroscience  Program.
■7730  ▼tDissertations  Abstracts  International▼g87-03B.
■790    ▼a0090
■791    ▼aPh.D.
■792    ▼a2023
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359985▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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