Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid
碩士 === 國立陽明大學 === 神經科學研究所 === 103 === Alzheimer’s disease (AD) is the most prevalent age-related dementia and the majority of AD cases are sporadic. The hallmarks of AD include senile plaques, neurofibrillary tangles and neuroinflammation. The population-base studies show that diabetes mellitus (DM)...
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ndltd-TW-103YM0052910192019-05-15T22:17:02Z http://ndltd.ncl.edu.tw/handle/8xr7ck Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid 高血糖降低星狀膠細胞清除乙型類澱粉蛋白能力之研究 Shu-Meng Hsu 許書夢 碩士 國立陽明大學 神經科學研究所 103 Alzheimer’s disease (AD) is the most prevalent age-related dementia and the majority of AD cases are sporadic. The hallmarks of AD include senile plaques, neurofibrillary tangles and neuroinflammation. The population-base studies show that diabetes mellitus (DM) is a risk factor of AD. Hyperglycemia and insulin resistance are hallmark of DM. Insulin signaling dysfunction and the inflammatory synergy may mediate the accelerating AD pathology by DM. Previous studies used pure microglia and astrocyte culture showed that glucose induces glial inflammatory response as acute stimuli. However, whether long-term exposure to high glucose induces glial inflammation or modulates glial immune response remains unclear. In this study, the mixed glia of astrocytes and microglia grown in medium contains 25 mM or 5.5 mM glucose was used to study the impact of long-term hyperglycemia on mixed glia. Our aim was focused on whether long-term exposure to high glucose modulates the immune response of mixed glia to LPS stimuli and oligomeric beta-amyloid (oAβ) clearance. Immunocytochemistry, real-time PCR and ELISA were applied. Our data suggest that long-term exposure to high glucose did not elevate the basal inflammatory levels of mixed glia. LPS induced IL-1β and IL-10 mRNA expression level and secretion of IL-1β in mixed glia grown in high glucose medium were not different from mixed glia grown in low glucose medium. Therefore, long-term expose to high glucose medium does not enhance LPS-induced activation of mixed glia. In microglia of mixed glia cultured in high and low glucose internalization and degradation of oAβ are similar. However, astrocytes of mixed glia cultured in low glucose internalized more oAβ and degrade oAβ faster. Furthermore, internalized oAβ punta by astrocytes is not colocalized with lysosome. In addition, the degradation of oAβ can be attenuated by proteasome inhibitor, MG132, indicating that proteasome may be the prominent compartment for the degradation of oAβ. This study is the first study reveals that long-term exposure to high glucose attenuates oAβ internalization and degradation by astrocytes. Huey-Jen Tsay 蔡惠珍 2015 學位論文 ; thesis 47 en_US |
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碩士 === 國立陽明大學 === 神經科學研究所 === 103 === Alzheimer’s disease (AD) is the most prevalent age-related dementia and the majority of AD cases are sporadic. The hallmarks of AD include senile plaques, neurofibrillary tangles and neuroinflammation. The population-base studies show that diabetes mellitus (DM) is a risk factor of AD. Hyperglycemia and insulin resistance are hallmark of DM. Insulin signaling dysfunction and the inflammatory synergy may mediate the accelerating AD pathology by DM. Previous studies used pure microglia and astrocyte culture showed that glucose induces glial inflammatory response as acute stimuli. However, whether long-term exposure to high glucose induces glial inflammation or modulates glial immune response remains unclear.
In this study, the mixed glia of astrocytes and microglia grown in medium contains 25 mM or 5.5 mM glucose was used to study the impact of long-term hyperglycemia on mixed glia. Our aim was focused on whether long-term exposure to high glucose modulates the immune response of mixed glia to LPS stimuli and oligomeric beta-amyloid (oAβ) clearance. Immunocytochemistry, real-time PCR and ELISA were applied.
Our data suggest that long-term exposure to high glucose did not elevate the basal inflammatory levels of mixed glia. LPS induced IL-1β and IL-10 mRNA expression level and secretion of IL-1β in mixed glia grown in high glucose medium were not different from mixed glia grown in low glucose medium. Therefore, long-term expose to high glucose medium does not enhance LPS-induced activation of mixed glia. In microglia of mixed glia cultured in high and low glucose internalization and degradation of oAβ are similar. However, astrocytes of mixed glia cultured in low glucose internalized more oAβ and degrade oAβ faster. Furthermore, internalized oAβ punta by astrocytes is not colocalized with lysosome. In addition, the degradation of oAβ can be attenuated by proteasome inhibitor, MG132, indicating that proteasome may be the prominent compartment for the degradation of oAβ. This study is the first study reveals that long-term exposure to high glucose attenuates oAβ internalization and degradation by astrocytes.
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author2 |
Huey-Jen Tsay |
author_facet |
Huey-Jen Tsay Shu-Meng Hsu 許書夢 |
author |
Shu-Meng Hsu 許書夢 |
spellingShingle |
Shu-Meng Hsu 許書夢 Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid |
author_sort |
Shu-Meng Hsu |
title |
Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid |
title_short |
Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid |
title_full |
Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid |
title_fullStr |
Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid |
title_full_unstemmed |
Hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid |
title_sort |
hyperglycemia attenuates astrocytic degradation of oligomeric beta amyloid |
publishDate |
2015 |
url |
http://ndltd.ncl.edu.tw/handle/8xr7ck |
work_keys_str_mv |
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