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Prodromal Dysfunction in Vagal Systems in the Pink1-/- Rat Model of Parkinson Disease
Prodromal Dysfunction in Vagal Systems in the Pink1-/- Rat Model of Parkinson Disease
Prodromal Dysfunction in Vagal Systems in the Pink1-/- Rat Model of Parkinson Disease

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202105132
ISBN  
9798291572504
DDC  
616
저자명  
Krasko, Maryann N.
서명/저자  
Prodromal Dysfunction in Vagal Systems in the Pink1-/- Rat Model of Parkinson Disease
발행사항  
[Sl] : The University of Wisconsin - Madison, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
285 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-02, Section: A.
주기사항  
Advisor: Ciucci, Michelle R.
학위논문주기  
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2025.
초록/해제  
요약Parkinson disease (PD) is increasingly understood as a disorder that affects multiple systems. Although best known for its hallmark motor disturbances, non-motor and other motor signs can manifest years prior to diagnosis during what is known as the prodromal stage of disease. These early signs often implicate vagal functions, resulting in early changes to gastrointestinal (GI) motility, swallowing, and vocalization. Despite their early manifestation, these prodromal signs remain understudied due to the challenges of identifying PD during its prodromal phase. Moreover, how sex influences the manifestation of these dysfunctions is not well understood. This dissertation uses the Pink1-/- rat, a well-established model of early-onset PD, to investigate vagal and non-vagal behaviors in both male and female rats in the prodromal stage.First, a preliminary study was completed to validate the Pink1-/- model for its use in studying swallowing and GI changes in 4-6-month-old male rats compared to wildtype (WT) controls. We hypothesized that Pink1-/- rats would demonstrate deficits in oropharyngeal swallowing and gastrointestinal motility at 4 months of age compared to healthy WT control rats. Results supported these hypotheses, as Pink1-/- rats exhibited slower mastication rates, reduced pharyngoesophageal bolus transit, increased abnormal swallowing behaviors, delayed colonic motility, and constipation-like signs. These findings confirmed the model's suitability for studying prodromal vagal dysfunction.Building on this foundation, the primary study examined vagally and non-vagally mediated behaviors at 4 months of age, expanding to include female rats, as well. Vocalizations (via ultrasonic vocalization analysis), swallowing and GI function (via videofluoroscopy), and limb motor performance (via Tapered Balance Beam) were assessed. We hypothesized that (1) Pink1-/- rats would show significantly decreased measures in vagal functions compared to WT controls, (2) Pink1-/- male rats would show significantly decreased measures in vagal functions compared to Pink1-/- females, and (3) male and female Pink1-/- rats would show significantly greater changes to vagal functions than limb motor function. Findings largely supported these hypotheses, as Pink1-/- rats showed significant deficits in GI function and semi-solid swallowing, as well as some vocal changes, while limb motor function remained relatively preserved. Sex-specific differences emerged primarily in GI outcomes, with Pink1-/- males showing the most pronounced deficits. Interestingly, sex differences in vocalization observed in WT rats were absent in Pink1-/- animals.Together, these findings indicate that vagally mediated functions are affected early in PD pathogenesis, potentially preceding traditional motor impairments. The identification of Pink1-/- and sex-specific patterns in prodromal dysfunction not only enhances our understanding of disease progression but also supports the use of vagal biomarkers for earlier diagnosis and targeted intervention strategies.
일반주제명  
Neurosciences
일반주제명  
Health sciences
일반주제명  
Speech therapy
일반주제명  
Communication
키워드  
Gastrointestinal motility
키워드  
Limb motor
키워드  
Parkinson disease
키워드  
Swallowing
키워드  
Vagus nerve
키워드  
Voice
기타저자  
The University of Wisconsin - Madison Communicative Disorders
기본자료저록  
Dissertations Abstracts International. 87-02A.
전자적 위치 및 접속  
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■035    ▼a(MiAaPQ)AAI32239266
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a616
■1001  ▼aKrasko,  Maryann  N.
■24510▼aProdromal  Dysfunction  in  Vagal  Systems  in  the  Pink1-/-  Rat  Model  of  Parkinson  Disease
■260    ▼a[Sl]▼bThe  University  of  Wisconsin  -  Madison▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a285  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-02,  Section:  A.
■500    ▼aAdvisor:  Ciucci,  Michelle  R.
■5021  ▼aThesis  (Ph.D.)--The  University  of  Wisconsin  -  Madison,  2025.
■520    ▼aParkinson  disease  (PD)  is  increasingly  understood  as  a  disorder  that  affects  multiple  systems.  Although  best  known  for  its  hallmark  motor  disturbances,  non-motor  and  other  motor  signs  can  manifest  years  prior  to  diagnosis  during  what  is  known  as  the  prodromal  stage  of  disease.  These  early  signs  often  implicate  vagal  functions,  resulting  in  early  changes  to  gastrointestinal  (GI)  motility,  swallowing,  and  vocalization.  Despite  their  early  manifestation,  these  prodromal  signs  remain  understudied  due  to  the  challenges  of  identifying  PD  during  its  prodromal  phase.  Moreover,  how  sex  influences  the  manifestation  of  these  dysfunctions  is  not  well  understood.  This  dissertation  uses  the  Pink1-/-  rat,  a  well-established  model  of  early-onset  PD,  to  investigate  vagal  and  non-vagal  behaviors  in  both  male  and  female  rats  in  the  prodromal  stage.First,  a  preliminary  study  was  completed  to  validate  the  Pink1-/-  model  for  its  use  in  studying  swallowing  and  GI  changes  in  4-6-month-old  male  rats  compared  to  wildtype  (WT)  controls.  We  hypothesized  that  Pink1-/-  rats  would  demonstrate  deficits  in  oropharyngeal  swallowing  and  gastrointestinal  motility  at  4  months  of  age  compared  to  healthy  WT  control  rats.  Results  supported  these  hypotheses,  as  Pink1-/-  rats  exhibited  slower  mastication  rates,  reduced  pharyngoesophageal  bolus  transit,  increased  abnormal  swallowing  behaviors,  delayed  colonic  motility,  and  constipation-like  signs.  These  findings  confirmed  the  model's  suitability  for  studying  prodromal  vagal  dysfunction.Building  on  this  foundation,  the  primary  study  examined  vagally  and  non-vagally  mediated  behaviors  at  4  months  of  age,  expanding  to  include  female  rats,  as  well.  Vocalizations  (via  ultrasonic  vocalization  analysis),  swallowing  and  GI  function  (via  videofluoroscopy),  and  limb  motor  performance  (via  Tapered  Balance  Beam)  were  assessed.  We  hypothesized  that  (1)  Pink1-/-  rats  would  show  significantly  decreased  measures  in  vagal  functions  compared  to  WT  controls,  (2)  Pink1-/-  male  rats  would  show  significantly  decreased  measures  in  vagal  functions  compared  to  Pink1-/-  females,  and  (3)  male  and  female  Pink1-/-  rats  would  show  significantly  greater  changes  to  vagal  functions  than  limb  motor  function.  Findings  largely  supported  these  hypotheses,  as  Pink1-/-  rats  showed  significant  deficits  in  GI  function  and  semi-solid  swallowing,  as  well  as  some  vocal  changes,  while  limb  motor  function  remained  relatively  preserved.  Sex-specific  differences  emerged  primarily  in  GI  outcomes,  with  Pink1-/-  males  showing  the  most  pronounced  deficits.  Interestingly,  sex  differences  in  vocalization  observed  in  WT  rats  were  absent  in  Pink1-/-  animals.Together,  these  findings  indicate  that  vagally  mediated  functions  are  affected  early  in  PD  pathogenesis,  potentially  preceding  traditional  motor  impairments.  The  identification  of  Pink1-/-  and  sex-specific  patterns  in  prodromal  dysfunction  not  only  enhances  our  understanding  of  disease  progression  but  also  supports  the  use  of  vagal  biomarkers  for  earlier  diagnosis  and  targeted  intervention  strategies.
■590    ▼aSchool  code:  0262.
■650  4▼aNeurosciences
■650  4▼aHealth  sciences
■650  4▼aSpeech  therapy
■650  4▼aCommunication
■653    ▼aGastrointestinal  motility
■653    ▼aLimb  motor
■653    ▼aParkinson  disease
■653    ▼aSwallowing
■653    ▼aVagus  nerve
■653    ▼aVoice
■690    ▼a0317
■690    ▼a0566
■690    ▼a0460
■690    ▼a0459
■71020▼aThe  University  of  Wisconsin  -  Madison▼bCommunicative  Disorders.
■7730  ▼tDissertations  Abstracts  International▼g87-02A.
■790    ▼a0262
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359523▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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