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Characterization of Mnz (SwAPP-Tshrhyt), a Novel Hybrid Mouse in the Linkage Between Hypothyroidism and Alzheimer's Disease /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Characterization of Mnz (SwAPP-Tshrhyt), a Novel Hybrid Mouse in the Linkage Between Hypothyroidism and Alzheimer's Disease /Carolina N Muniz Partida.
作者:	Muniz Partida, Carolina N.,
面頁冊數:	1 electronic resource (150 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
附註:	Advisors: Walters, Eric Committee members: Sherif, Zaki; Richardson, Kimberlei; Allard, Joanne.
Contained By:	Dissertations Abstracts International86-03B.
標題:	Neurosciences.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31293344
ISBN:	9798384041344

Characterization of Mnz (SwAPP-Tshrhyt), a Novel Hybrid Mouse in the Linkage Between Hypothyroidism and Alzheimer's Disease /
Muniz Partida, Carolina N.,

Characterization of Mnz (SwAPP-Tshrhyt), a Novel Hybrid Mouse in the Linkage Between Hypothyroidism and Alzheimer's Disease /Carolina N Muniz Partida. - 1 electronic resource (150 pages)

Source: Dissertations Abstracts International, Volume: 86-03, Section: B.

The etiology of Alzheimer's disease (AD) remains unclear, to elucidate the molecular and biochemical mechanisms in AD pathology is an important subject of investigation. The formation of amyloid beta (Aβ) plaques in the brain cortex is linked to the cognitive dysfunction of AD. Research in AD is bolstered by the development of transgenic "humanized" mouse models that resemble accumulation of Aβ deposits in the CNS that results in the pathogenesis of AD. Recent findings suggest that clinical hypothyroidism and the use of anti-thyroid drugs in rodents may shed light on factors that affect AD phenotype, such as increased numbers of Aβ (insoluble deposits) and memory impairment. Development of a mouse model that displays characteristics of a) hypothyroidism and b) Aβ-plaque formation could bridge the gap of knowledge between these variables and AD pathology. The Tg-SwAPP transgenic mouse is an AD model that harbors mutations of the amyloid precursor protein (APP) leads to the development of Aβ plaques. The TSHR+/hyt mouse possesses a point mutation (Pro 556- Leu) in the thyroid stimulating hormone receptor (TSHR), that alters the synthesis of thyroxine, resulting in mild (+/hyt) or severe (hyt/hyt) forms of hypothyroidism. The first Aim of this study was to strategically breed of SwAPP and TSHR+/hyt mice and generate a hybrid mouse strain that displays hypothyroid and AD phenotypes. Aim 2 was to characterize key features and cellular phenotypes of the hybrid SwAPP-TSHR+/hyt brain cortical and hippocampus regions, such as Aβ plaque accumulation, proliferating cell nuclear antigen (PCNA), and glial fibrillary acidic protein (GFAP) (neuroinflammatory markers) levels in aged mice. The transcriptional levels of the secretases responsible (ADAM10) for APP processing were also be measured. Finally, Aim 3 assessed cognitive function and behavior of SwAPP-Tshrhyt relative to thyroid status and genotype, using the novel object recognition and Y-maze test to analyze retentive and working memory. This established SwAPP-Tshrhyt model has the potential to further elucidate the influence of hypothyroidism on the progression of AD. Immunohistochemistry and Western blot analyses revealed increased GFAP expression and Aβ plaque accumulation in hypothyroid T-SwAPP mice, particularly worsening with age, indicating a potential link between thyroid dysfunction and neuroinflammation. Furthermore, the observed differences in plaque accumulation between mild and severe hypothyroidism prompt intriguing questions regarding the role of endogenous APP in modulating Aβ deposition. Additionally, TSHR instability may contribute to altered hippocampal neurogenesis through mechanisms involving ER stress and GPCR misfolding, highlighting the complexity of TSHR signaling in AD pathology. Lastly, behavioral tests in the T-SwAPP mouse model underscore the importance of TSHR signaling in hippocampal-dependent memory formation, suggesting a potential therapeutic target for mitigating cognitive decline in AD.

English

ISBN: 9798384041344Subjects--Topical Terms:

211508
Neurosciences.
Subjects--Index Terms:

Immunohistochemistry

Characterization of Mnz (SwAPP-Tshrhyt), a Novel Hybrid Mouse in the Linkage Between Hypothyroidism and Alzheimer's Disease /
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520 $a The etiology of Alzheimer's disease (AD) remains unclear, to elucidate the molecular and biochemical mechanisms in AD pathology is an important subject of investigation. The formation of amyloid beta (Aβ) plaques in the brain cortex is linked to the cognitive dysfunction of AD. Research in AD is bolstered by the development of transgenic "humanized" mouse models that resemble accumulation of Aβ deposits in the CNS that results in the pathogenesis of AD. Recent findings suggest that clinical hypothyroidism and the use of anti-thyroid drugs in rodents may shed light on factors that affect AD phenotype, such as increased numbers of Aβ (insoluble deposits) and memory impairment. Development of a mouse model that displays characteristics of a) hypothyroidism and b) Aβ-plaque formation could bridge the gap of knowledge between these variables and AD pathology. The Tg-SwAPP transgenic mouse is an AD model that harbors mutations of the amyloid precursor protein (APP) leads to the development of Aβ plaques. The TSHR+/hyt mouse possesses a point mutation (Pro 556- Leu) in the thyroid stimulating hormone receptor (TSHR), that alters the synthesis of thyroxine, resulting in mild (+/hyt) or severe (hyt/hyt) forms of hypothyroidism. The first Aim of this study was to strategically breed of SwAPP and TSHR+/hyt mice and generate a hybrid mouse strain that displays hypothyroid and AD phenotypes. Aim 2 was to characterize key features and cellular phenotypes of the hybrid SwAPP-TSHR+/hyt brain cortical and hippocampus regions, such as Aβ plaque accumulation, proliferating cell nuclear antigen (PCNA), and glial fibrillary acidic protein (GFAP) (neuroinflammatory markers) levels in aged mice. The transcriptional levels of the secretases responsible (ADAM10) for APP processing were also be measured. Finally, Aim 3 assessed cognitive function and behavior of SwAPP-Tshrhyt relative to thyroid status and genotype, using the novel object recognition and Y-maze test to analyze retentive and working memory. This established SwAPP-Tshrhyt model has the potential to further elucidate the influence of hypothyroidism on the progression of AD. Immunohistochemistry and Western blot analyses revealed increased GFAP expression and Aβ plaque accumulation in hypothyroid T-SwAPP mice, particularly worsening with age, indicating a potential link between thyroid dysfunction and neuroinflammation. Furthermore, the observed differences in plaque accumulation between mild and severe hypothyroidism prompt intriguing questions regarding the role of endogenous APP in modulating Aβ deposition. Additionally, TSHR instability may contribute to altered hippocampal neurogenesis through mechanisms involving ER stress and GPCR misfolding, highlighting the complexity of TSHR signaling in AD pathology. Lastly, behavioral tests in the T-SwAPP mouse model underscore the importance of TSHR signaling in hippocampal-dependent memory formation, suggesting a potential therapeutic target for mitigating cognitive decline in AD.
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