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Identifier

000403330

Title

Role of genomic instability in CNS immune cells : cell autonomous response of microglia-specific Ercc1 knockout

Alternative Title

Ο ρόλος της γονιδιωματικής αστάθειας στην έμφυτη ανοσία του κεντρικού νευρικού συστήματος: κυτταροαυτόνομη απόκριση του Ercc1 knockout στα κύττρα μικρογλοίας

Author

Ρούσκα, Ηλιάνα Δ.

Thesis advisor

Γαρίνης, Γεώργιος

Reviewer

Ηλιόπουλος, Ελευθέριος
Μπερτσιάς, Γεώργιος

Abstract

Normal aging and progeroid syndromes have been associated with degenerative changes of Central Nervous System (CNS). Nowadays, increasing evidence suggest that abnormal reactionsof microglia, the immune cells of the brain, contribute tο age-related deterioration of the neuronal pathology. However, it is unclear whether the response is due to micro-environmental or intrinsic factors. In this master thesis, adult mice, bearing microglia-specific disruption of ERCC1-XPF damage factor, were examined, in order to delineate its cell autonomous response. According to our data the ERCC1 ablation causes accumulating, unrepaired DNA damage to the microglia, leading to activation of DNA damage response (DDR) dependent on the ATM pathway. Damage sensors were also detected to be present in the cytosol, but their role is not yet defined. Furthermore, we find change of cell morphology through a transition from resting to activated form, a phenotype connected to both activated and senescent microglia. Summarizing, our data show the first signs that increased genotoxic damage can alter the functional and morphological properties of microglial cells.

Language

English

Subject

ATM

Accelerating aging

Neurodegenerative abnormalities

Neurodevelopmental

Nucleotide Excision Repair (NER)

ΓΗ2ΑΧ

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