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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 Μουάτσου, Χρυσή
Thesis advisor Καράλη, Κανελίνα
Χαραλαμπόπουλος, Ιωάννης
Reviewer Γιακουμάκη, Στέλλα
Σιδηροπούλου, Κυριακή
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.
Language English
Subject Adult neurogenesis
DHEA synthetic analog
Dentate gyrus
Microneurotrophins
Subventricular zone
Ενήλικη νευρογένεση
Μικρονευροτροφίνες
Οδοντωτή έλικα
Συνθετικό ανάλογο δευδροεπιανδροστερόνης
Υποκοιλιακή ζώνη
Issue date 2023-12-08
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/d/9/a/metadata-dlib-1701170327-689959-9325.tkl Bookmark and Share
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