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Identifier |
000458952 |
Title |
The role of myelinophagy in central nervous system (CNS) development |
Alternative Title |
Ο ρόλος της μυελινοφαγίας στην ανάπτυξη του κεντρικού νευρικού συστήματος (ΚΝΣ) |
Author
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Κτένα, Νίκη
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Thesis advisor
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Καραγωγέως, Δόμνα
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Reviewer
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Νικολετοπούλου, Βασιλική
Σιδηροπούλου, Κυριακή
Ζούπη, Λήδα
Βιδάκη, Μαρίνα
Μπαζοπούλου, Δάφνη
Χαραλαμπόπουλος, Ιωάννης
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Abstract |
Macro)autophagy consists an evolutionarily conserved pathway delivering unwanted cytoplasmic material, including damaged organelles and toxic protein aggregates, to lysosomes for degradation. Despite certain investigations linking autophagy to central nervous system (CNS) demyelinating disorders, its precise role, especially concerning mature oligodendrocytes and CNS myelin, remains insufficiently explored. In this study, through both pharmacological and genetic inhibition of the autophagic process, we present compelling evidence that autophagy constitutes a vital mechanism governing oligodendrocyte maturation in vitro. Moreover, our findings unveil that two fundamental myelin proteins, namely proteolipid protein (PLP) and myelin basic protein (MBP), are incorporated into autophagosomes in oligodendrocytes, subsequently leading to their degradation. Furthermore, by selectively ablating the core autophagic gene atg5 within myelinating glial cells in vivo through tamoxifen administration (plp-CreERT2; atg5 f/f) at different developmental windows, we provide evidence about the role of autophagy in myelin formation, myelin maintenance in adulthood and myelin maintenance during aging. Our data indicate that autophagy depletion prior to myelination onset does not have any significant impact in myelin status. Conversely, autophagy depletion in adulthood leads to severe structural defects in the adult myelin membrane coupled with increased axonal degeneration. Consequently, these mice display behavioral deficits, such as motor learning impairments. Similar deficiencies are also observed in aged mice, simultaneously accompanied by increased microglia activation. To summarize, our findings underscore the necessity of a fully operational autophagic process for maintaining myelin homeostasis in the adult and aged CNS, providing evidence that autophagy within oligodendrocytes may intercede myelin turnover.
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Language |
English |
Subject |
Autophagy |
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Myelin |
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Oligodendrocyte |
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Αυτοφαγία |
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Μυελίνη |
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Ολιγοδενδροκύτταρο |
Issue date |
2023-12-08 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/f/a/2/metadata-dlib-1696233027-828351-28906.tkl
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Views |
1033 |
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