Abstract | AIMS: METHODS: APP/PS1 mice and AD cell model induced by Aβ 25-35 were selected as the research objects. APP/PS1 mice were daily administrated intragastrically with progesterone and The Morris Water Maze test was performed to detect the learning and memory abilities. Intracellular cholesterol was measured by Cholesterol/ Cholesteryl Ester Quantitation Assay. The structure of MAMs were observed with transmission electron microscopy. The expression of acyl-CoA: cholesterol acyltransferase 1 (ACAT1), ERK1/2 and p-ERK1/2 were detected with western blotting, immunohistochemistry or immunofluorescence. RESULTS:
Progesterone suppressed the accumulation of intracellular CE, shortened the length of abnormally prolonged MAM in cortex of APP/PS1 mice. Progesterone decreased the expression of ACAT1, which could be blocked by progesterone receptor membrane component 1 (PGRMC1) inhibitor AG205. The ERK1/2 pathway maybe involved in the progesterone mediated regulation of ACAT1 in AD models, rather than the PI3K/Akt and the P38 MEPK pathways. SIGNIFICANCE: The results supported a line of evidence that progesterone regulates CE level and the structure of MAM in neurons of AD models, providing a promising treatment against AD on the dysfunction of cholesterol metabolism.
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Authors | Wenjing Shi, Hang Wu, Sha Liu, Zhigang Wu, Honghai Wu, Jianfang Liu, Yanning Hou |
Journal | Brain research bulletin
(Brain Res Bull)
Vol. 173
Pg. 162-173
(08 2021)
ISSN: 1873-2747 [Electronic] United States |
PMID | 34044033
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 Elsevier Inc. All rights reserved. |
Chemical References |
- Amyloid beta-Protein Precursor
- Cholesterol Esters
- Presenilin-1
- Progesterone
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Topics |
- Alzheimer Disease
(genetics, metabolism)
- Amyloid beta-Protein Precursor
(genetics, metabolism)
- Animals
- Brain
(drug effects, metabolism)
- Cholesterol Esters
(metabolism)
- Disease Models, Animal
- Esterification
- Male
- Mice
- Mice, Transgenic
- Neurons
(metabolism)
- Presenilin-1
(genetics, metabolism)
- Progesterone
(pharmacology)
- Rats
- Rats, Sprague-Dawley
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