Post-graduate theses
Current Record: 775 of 6663
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| Identifier |
000444063 |
| Title |
Investigation of the prefrontal cortical structure and function following ablation of autophagy in projection neurons during adolescence |
| Alternative Title |
Μελέτη της δομής και λειτουργίας του προμετωπιαίου φλοιού έπειτα από μείωση της αυτοφαγίας στους προβλητικούς νευρώνες κατά την εφηβεία |
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Author
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Παραπέρα-Παπαντωνίου Λητώ Δ.
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Thesis advisor
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Σιδηροπούλου, Κυριακή
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Reviewer
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Νικολετουπούλου, Βασιλική
Χαραλαμπόπουλος, Ιωάννης
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| Abstract |
Autophagy is a cellular process that promotes the removal of dysfunctional or unnecessary products via lysosome-dependent pathways. Autophagy has been associated with the mechanisms underlying the pruning of excitatory synapses that normally occurs during development and it is believed that its dysregulation could lead to neurodevelopmental diseases. The prefrontal cortex is a brain area involved in higher-order cognitive function and exhibits slower maturation compared to other cortical areas. Here, we aimed to understand whether inhibiting autophagy during the synaptic pruning period of the PFC (post-natal day (P)35-p45) affects dendritic spine density in the PFC and its function. For this purpose, thy1-CreERT2;atg5f/f (KO) mice were generated, which lack Atg5-a gene necessary for the elongation of the phagophore during the process of autophagy-in projection neurons expressing Thy1. Tamoxifen (tmx) was post-injected to mice on P31-35 or P61-65 (as a control), to induce Cre activity and lead to autophagy impairment. A milder autophagy impairment was enabled in thy1-CreERT2;atg5+/fl (heterozygotes or Het) animals. After P80, all mice were tested in the following: Novel Object Recognition (NOR), Object-To-Place (OTP), Temporal Order Object Recognition (TOR) tasks, and Three-Chamber Sociability test. Dendritic spine morphology and density of these animals’ pyramidal neurons were studied using optical microscopy following Golgi-cox staining. A tendency towards increased spine densities, especially in the case of mature spines, in the PFC of animals whose neuronal autophagy was impaired during adolescence (P31-P35) or early adulthood (P61-P65) was observed. Autophagy impairment during adolescence or early adulthood did not exert significant effects on sociability or social memory. However, neuronal autophagy impairment during adolescence resulted in recency and spatial memory deficits, as well as in deficits in novelty-recognition. Deficits in spatial memory were also observed in animals with impaired autophagy during early adulthood. Therefore, our results suggest that deficient autophagy after P30 results in increased dendritic spine density in the PFC and impaired performance in NOR, OTP, and TOR tasks.
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| Language |
English |
| Subject |
Development |
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Prefrontal cortex |
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Synaptic pruning |
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Ανάπτυξη |
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Αυτοφαγία |
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Κλάδεμα συνάψεων |
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Προμετωπιαίος φλοιός |
| Issue date |
2022-07-29 |
| 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/9/1/5/metadata-dlib-1638349336-807970-2711.tkl
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| Views |
457 |
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