Evaluation of a Potential Mechanism of Sudden Unexpected Death in Epilepsy in a Mouse Model of Dravet Syndrome- [electronic resource]
Evaluation of a Potential Mechanism of Sudden Unexpected Death in Epilepsy in a Mouse Model of Dravet Syndrome- [electronic resource]
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214100109
- ISBN
- 9798380130356
- DDC
- 615
- 저자명
- Goh, Min-Jee.
- 서명/저자
- Evaluation of a Potential Mechanism of Sudden Unexpected Death in Epilepsy in a Mouse Model of Dravet Syndrome - [electronic resource]
- 발행사항
- [S.l.]: : The University of Utah., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(173 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-02, Section: B.
- 주기사항
- Advisor: Metcalf, Cameron Spencer.
- 학위논문주기
- Thesis (Ph.D.)--The University of Utah, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약The incidence of Sudden Unexpected Death in Epilepsy (SUDEP) is especially high in those with Dravet syndrome (DS), a rare, pediatric genetic epilepsy. Respiratory dysfunction has been shown to be a primary contributor to SUDEP, but the mechanism by which this sudden death occurs is not fully understood. We assess baseline and post-seizure breathing patterns in a mouse model of DS. We determine neuronal excitability in a key brainstem respiratory center to determine if its hypoactivity may contribute to diminished breathing patterns. We also investigate a potential glial-mediated mechanism of respiratory dysregulation and SUDEP, investigating markers of glial reactivity and inflammation in several brainstem respiratory nuclei. Glia play active roles in maintaining neuronal function and CNS homeostasis. When glia such as astrocytes and microglia become reactive, as they do with CNS insults such as seizures, they lose their homeostatic functions and can cause neuronal dysfunction. A longitudinal whole body plethysmography study revealed diminished breathing in the Scn1aA1783V DS mice, particularly after seizure in younger DS animals that are most susceptible to death. This diminished breathing was characterized by a slow, low effort inhalation, possibly implicating inspiration-generating centers of the brain in SUDEP. The nucleus of the solitary tract (NTS), a key brainstem center involved in regulating breathing, did not differ in excitability or synaptic efficacy in DS mice compared to WT and may not be directly involved in the breathing patterns we observed in the DS mice. There was no glial reactivity or inflammation in the NTS; however, astrocyte reactivity and pro-inflammatory cytokine IL-6 upregulation were present in the amygdala, a brain region that has been documented as producing apnea when stimulated experimentally or by a seizure. These data elucidate detailed breathing patterns that occur after seizure in DS and allow us to begin to understand a potential role of astrocyte reactivity and inflammation in SUDEP. These results also provide new direction for future studies, such as further investigating the amygdala and inspiration-generating centers of the ventral respiratory column and the neuronal consequences on astrocyte reactivity and IL-6 elevation.
- 일반주제명
- Pharmacology.
- 일반주제명
- Neurosciences.
- 일반주제명
- Toxicology.
- 키워드
- Dravet syndrome
- 기타저자
- The University of Utah Pharmacology and Toxicology
- 기본자료저록
- Dissertations Abstracts International. 85-02B.
- 기본자료저록
- Dissertation Abstract International
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