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https://hdl.handle.net/123456789/903
Τύπος: | Διδακτορική διατριβή |
Τίτλος: | Study of the effects of mutant alpha-synuclein in models of Parkinson’s disease |
Συγγραφέας: | [EL] Ζυγογιάννη, Ουρανία[EN] Zygogianni, Ourania |
Επιβλέπων διατριβής: | [EL] Στυλιανοπούλου, Φωτεινή[EN] Stylianopoulou, Fotini |
Συμβουλευτική επιτροπή: | [EL] Μάτσα, Ρεβέkκα[EN] Matsas, Rebecca [EL] Σταματάκης, Αντώνιος[EN] Stamatakis, Antonios |
Μέλος εξεταστικής επιτροπής: | [EL] Ευθυμιόπουλος, Σπυρίδων[EN] Efthimiopoulos, Spiros [EL] Στεφανής, Λεωνίδας[EN] Stefanis, Leonidas [EL] Παναγιωτακοπούλου, Μαρία[EN] Panayotacopoulou, Maria [EL] Θωμαΐδου, Δήμητρα[EN] Thomaidou, Dimitra |
Ημερομηνία: | 2019 |
Περίληψη: | Parkinson’s disease (PD) is the second most common neurodegenerative disorder. We have previously developed a disease-ina- dish model for familial PD using induced pluripotent stem cells (iPSCs) from two patients carrying the p.A53T α-synuclein (αSyn) mutation. By directed differentiation, we generated a model that displays disease-relevant phenotypes, including protein aggregation, compromised neurite outgrowth, axonal neuropathology and synaptic defects. Here we investigated the in vivo phenotypes of iPSCs, derived from one patient, after transplantation in a lesion mouse model established by unilateral intrastriatal 6-hydroxydopamine injection in the immunosuppressed NOD/SCID strain. Immunohistochemistry revealed that despite the disease-related characteristics that mutant cells displayed when maintained up to 70 days in vitro, they could survive and differentiate in vivo over a 12-week period. However, some differences were noted between patient-derived and control grafts, including a significant rise in αSyn immunoreactivity that might signal a first step towards pathology. Moreover, control-derived grafts appeared to integrate better than PD grafts within the host tissue extending projections that formed more contacts with host striatal neurons. Our data suggest that the distinct disease-related characteristics which p.A53T cells develop in vitro, may be attenuated or take longer to emerge in vivo after transplantation within the mouse brain. Further analysis of the phenotypes that patient cells acquire over longer periods of time as well as the use of multiple iPSC clones from different patients should extend our current proof-of-concept study and provide additional evidence for in vivo disease modeling. |
Γλώσσα: | Αγγλικά |
Τόπος δημοσίευσης: | Athens, Greece |
Σελίδες: | 181 |
Θεματική κατηγορία: | [EL] Ιατρική βιοχημεία[EN] Medical Biochemistry |
Λέξεις-κλειδιά: | a-synuclein |
Κάτοχος πνευματικών δικαιωμάτων: | © Ουρανία Ζυγογιάννη |
Όροι και προϋποθέσεις δικαιωμάτων: | For the English language all over the world. Intellectual property is obtained without any formulation and without the need for clause prohibiting its infringement. It should be noted, however, that under Law 2387/20 (as amended by Law No. 100/1975 and still in force) and under the International Convention of Berne (as ratified by Law No. 100/1975), republishing is prohibited, the storage in any saving system and generally the reproduction of the present work, in any way or form, in whole or in part, in the original or in translation or other adaptation without the written permission of the author. |
Διατίθεται ανοιχτά στην τοποθεσία: | https://www.didaktorika.gr/eadd/handle/10442/44960 |
Σημειώσεις: | Παρακαλώ να μην είναι διαθεσιμο το κείμενο μέχρι τον Ιανουάριο του 2022 (3 χρόνια από τη δημιούργία της διατιβής) O.Z. was awarded a scholarship from the State Scholarship Foundation (IKY) funded by the Action “Scholarships for post-graduate studies” (Operational Program “Education and Lifelong learning”, 2014-2020) and co-financed by the European Social Fund and the Greek government. |
Εμφανίζεται στις συλλογές: | Υποψήφιοι διδάκτορες |
Αρχεία σε αυτό το τεκμήριο:
Αρχείο | Περιγραφή | Σελίδες | Μέγεθος | Μορφότυπος | Έκδοση | Άδεια | |
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Zygogianni Ourania PhD.pdf | Διδακτορική Διατριβή | 181 σελίδες σελίδες | 5.96 MB | Adobe PDF | Άλλη | Δείτε/ανοίξτε |