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Identifier |
000460392 |
Title |
Sex differences in cholesteol metabolism in two Alzheimer's disease mouse models |
Alternative Title |
Φυλετικές διαφορές στον μεταβολισμό της χοληστερόλης σε δύο μοντέλα μυών με νόσο Alzheimer |
Author
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Νικολιδάκης, Ορέστης
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Thesis advisor
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Silvia maioli
Maria Latorre Leal
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Reviewer
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Χαραλαμπόπουλος, Ιωάννης
Ζαγανάς, Ιωάννης
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Abstract |
Alzheimer’s disease (AD) is a severe neurodegenerative disorder affecting older people worldwide, with a characteristic progressive cognitive decline. Some of the most important risk factors include elevated levels of serum cholesterol and the carriage of the lipoprotein transporter apolipoprotein E (ApoE) allele ε4. Since the brain is separated from peripheral circulation by the blood brain barrier (BBB), brain cholesterol is almost completely synthesized in situ. Cholesterol homeostasis in the central nervous system (CNS) is regulated through the conversion of cholesterol into oxidized metabolites called oxysterols, mainly consisting of 24-(S)-hydroxycholesterol (24S-OH) and 27-hydroxycholesterol (27-OHC) that unlike cholesterol, can diffuse through BBB. 24S-OH is formed in the brain, flows into the circulation and is further catabolized into bile acids in the liver, while 27-OH enters the brain from the periphery. These oxysterols have been reported to be altered in AD and probably play an important role in the development and progression of the disease. In this study, we determined how genes involved in cholesterol synthesis and homeostasis change in AD mouse models (APP-knock in), at different ages and whether they show sex-dependent differences. Our results showed that in the NLGF mice, there is a chronologically differentiated gene expression between the two sexes. These alterations initiate from 2 to 6 months in the males while they start after 6 expanding to 12 months in the females. These results were further supported by protein levels showing a correlation between CYP46A1, inflammation and lipid droplets marker levels. On the other hand, NLF mice don’t seem to show any significant sex differences across the ages measured probably due to the milder amyloid pathology of the model. Further studies should be conducted in human samples to validate our results and better understand the mechanism underlying these sex differences.
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Language |
English |
Subject |
27-υδροχοληστερόλη |
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Cholesterol homeostasis |
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Lipid droplets |
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Oxysterols |
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Ομοιόσταση χοληστερόλης |
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Οξυστερόλες |
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Σταγονίδια λιπιδίων |
Issue date |
2023-12-08 |
Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/a/f/f/metadata-dlib-1700135572-393912-21962.tkl
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Views |
933 |
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