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Search command : Author="Τσακάνι"
And Author="Εντισόνα"
And Author="Π."
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Identifier |
000434255 |
Title |
DNA damage – induced inflammation in neurodegeneration |
Alternative Title |
Μελέτη του ρόλου της φλεγμόνης που επάγεται από την συσσώρευση γενετικών βλαβών |
Author
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Τσακάνι, Εντισόνα Π.
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Thesis advisor
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Γαρίνης, Γεώργιος
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Abstract |
Microglia cells are the tissue-resident macrophages of the Central Nervous System (CNS), which
therefore act as the first and main form of active immune defense in the brain. Microglia promote
phagocytic clearance, provide trophic support to ensure tissue repair, protect neurons and maintain
brain homeostasis. In this study we used a monocyte/macrophage-specific Ercc1-/- mouse
(Cx3cr1-Cre) model, which was generated for the investigation of the consequences of DNA repair
impairment in tissue-resident macrophages. Led by the animal’s phenotype, which resembled
cerebellar ataxia- like neuropathology, we shifted our focus on microglia in the cerebellum. Here,
we demonstrate that DNA damage accumulation in microglia cells, results in the presence of
cytoplasmic damaged chromatin fragments, potentially through nucleophagy. Cytoplasmic DNA not
only triggers microglia priming in a cell autonomous manner through type I IFN response, but is
also carried in exosomes, and therefore get secreted to the extracellular space. We suggest that the
combination of type I IFN response activation and exososomal secretion promotes Purkinje cell
apoptosis and thus neurodegeneration. Overall, this research aims at investigating if DNA damage
accumulation occuring in microglia affects or results in age-related neuropathology. In vivo
experiments, using exosomes loaded with DnaseI were also performed as an attempt for potential
therapy and reversion of the animal’s phenotype.
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Language |
English, Greek |
Subject |
Microglia |
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Γενετικές βλάβες |
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Μικρογλοία |
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Νευροεκφυλισμός |
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Φλεγμόνη |
Issue date |
2020-11-27 |
Collection
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School/Department--School of Sciences and Engineering--Department of Biology--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/d/7/9/metadata-dlib-1606376261-836311-17533.tkl
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Views |
326 |