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Identifier |
000460611 |
Title |
Investigating the neurogenic effects of BNN237 in mouse model of stress |
Alternative Title |
Η διερεύνηση των επιδράσεων του ΒΝΝ237 στη νευρογένεση σε έννα ζωικό μοντέλο στρες |
Author
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Μουάτσου, Χρυσή
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Thesis advisor
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Καράλη, Κανελίνα
Χαραλαμπόπουλος, Ιωάννης
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Reviewer
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Γιακουμάκη, Στέλλα
Σιδηροπούλου, Κυριακή
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Abstract |
Background: Adult neurogenesis represents a dynamic field of neuroscience research,
as accumulating evidence supports that the generation of new neurons and their integration into
the existing neural circuits within the adult mammalian brain is associated with various
functional outcomes. Its potential role in brain plasticity renders adult neurogenesis a
compelling target for exploration in the context of therapeutic interventions for
neurodegenerative diseases. The process of neurogenesis is regulated by various factors,
including stress exposure and neurotrophins. Although chronic stress is associated with
diminished neurogenic capacity, the exact underlying mechanisms are not fully understood.
Conversely, neurotrophins are linked with enhanced neurogenesis, while it is suggested that
they might play a significant role in the association between neurogenesis and stress. The aim
of the present study was to investigate the neurogenic effects of BNN237, a novel blood-brainbarrier-
permeable steroid derivative of dehydroepiandrosterone (DHEA), in a mouse model of
stress. Methods: Using immunofluorescence analysis, the densities of newborn, proliferating
cells and immature neurons were evaluated in the two main neurogenic brain areas, the
subventricular zone (SVZ) and the dentate gyrus (DG) of mice receiving placebo or BNN237
via subcutaneous pellet under control or chronic stress conditions. In addition, mRNA levels of
various genes were assessed using rt-PCR analysis. Results: Our results confirmed preliminary
data demonstrating that BNN237 can increase newly formed proliferating cells in the SVZ. In
the olfactory bulbs (OB), the area where SVZ-derived newborn cells migrate, we observed a
diminishing effect of stress in the number of neuroblasts, but also a significant interaction
emerged between BNN237 treatment and stress, resulting in enhanced DCX-positive neuroblast
density in non-stress conditions. Interestingly, BNN237 did not exhibit significant effects on
the neurogenic capacity of the DG, while stress appeared to induce a trend toward reduced
proliferation in this area. Finally, we did not detect differences in the expression levels of
neurogenesis- and neurotrophin-related genes. Conclusions: Our findings confirm the proneurogenic
effects of BNN237 in the SVZ, while differences between the two main neurogenic
niches of the brain (SVZ and DG) may explain the restriction of these effects only in SVZ.
Furthermore, future studies should emphasize the interplay between neurotrophins and stress
hormones, as a possible mediator of the stress-related suppression of adult neurogenesis.
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Language |
English |
Subject |
Adult neurogenesis |
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DHEA synthetic analog |
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Dentate gyrus |
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Microneurotrophins |
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Subventricular zone |
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Ενήλικη νευρογένεση |
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Μικρονευροτροφίνες |
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Οδοντωτή έλικα |
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Συνθετικό ανάλογο δευδροεπιανδροστερόνης |
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Υποκοιλιακή ζώνη |
Issue date |
2023-12-08 |
Collection
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School/Department--School of Medicine--Department of Medicine--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/9/a/metadata-dlib-1701170327-689959-9325.tkl
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Views |
1151 |
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