자료유형  

 학위논문

Control Number  

0017162060

International Standard Book Number  

9798383046500

Dewey Decimal Classification Number  

616

Main Entry-Personal Name  

Salzbank, Jacquelyn Moriya.

Publication, Distribution, etc. (Imprint  

[S.l.] : Columbia University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

156 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

General Note  

Advisor: Penn, Anna.

Dissertation Note  

Thesis (Ph.D.)--Columbia University, 2024.

Summary, Etc.  

요약The placenta plays a vital role in a healthy pregnancy by supporting the intricacies of fetal development. Over 10% of pregnancies experience impaired placental function, resulting in the loss of critical neuroactive steroids the fetal brain cannot yet make, thus leaving them vulnerable to perinatal brain injury and abnormal neurodevelopment. However, this vulnerability is not always equal. Many neurodevelopmental disorders exhibit a sex bias in incidence and severity. I hypothesize that loss of placental support during pregnancy results in sex differences in both behavioral presentation as well as on the cellular and transcriptomic levels. Utilizing the akr1c14cyp19aKO (plKO) mouse model, which features placenta-specific allopregnanolone (ALLO) knockdown, I investigated the sex specific impact of placental hormones on cerebellar development. Here I show that placental ALLO is essential for cerebellar white matter development and inflammatory regulation via microglial function. Male mice without placental ALLO exhibit signs of placental inflammation, accelerated postnatal myelination, and defects in microglial phagocytosis of excess myelin. Alternatively, females seem to be more resilient with a progressive anti-inflammatory profile across development and reduced myelination. Additionally male plKO show autism- like behaviors such as deficits in social behavior and increased stereotyped behavior. The females do not exhibit this phenotype. My main goals were threefold; to investigate how male and female inflammatory profiles differ and where this difference originates, to investigate how this inflammation impacts microglia and thereby oligodendrocytes, and how I can alter microglial function in a way to improve plKO outcomes. Mechanistically, these changes appear to be in part due to baseline sex differences in response to inflammatory stimuli which prime microglia to differentially support the surrounding white matter. Together, this work supports a novel link between placental ALLO loss, microglial function, and sex specific presentation of neurodevelopmental disorders.

Subject Added Entry-Topical Term  

Neurosciences.

Subject Added Entry-Topical Term  

Obstetrics.

Subject Added Entry-Topical Term  

Developmental psychology.

Index Term-Uncontrolled  

Autism spectrum disorder

Index Term-Uncontrolled  

Cerebellum

Index Term-Uncontrolled  

Microglia

Index Term-Uncontrolled  

Myelination

Index Term-Uncontrolled  

Neuroplacentology

Index Term-Uncontrolled  

Placenta

Added Entry-Corporate Name  

Columbia University Cellular Molecular and Biomedical Studies

Host Item Entry  

Dissertations Abstracts International. 85-12B.

Electronic Location and Access  

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Control Number  

joongbu:656766