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Identifier

000433993

Title

In vitro study of the effects of endogenous and synthetic neurotrophins in the survivability of neuronal cells

Alternative Title

In vitro μελέτη της επίδρασης ενδογενών και συνθετικών νευροτροφινών στην επιβίωση νευρικών κυττάρων

Author

Τσιμπόλης, Αλέξανδρος

Thesis advisor

Χαραλαμπόπουλος, Ιωάννης

Reviewer

Γραβάνης, Αχιλλέας
Ζαγανάς, Ιωάννης

Abstract

Neurotrophins are necessary for the normal development and functioning of the central nervous system (CNS). Acting primarily through their tyrosine receptor kinase (Trk) receptors, they protect the neurons and ensure their survival and well-being. Dehydroepiandrosterone (DHEA) steroid hormone and its novel synthesized derivatives, microneurotrophins (BNNs), also exhibit significant neuroprotective properties, which they too exert through Trk signaling. In vivo experiments in 5xFAD mice, revealed decreased Aβ plaque formation in the hippocampus and increased proliferation and neuronal generation in the dentate gyrus, thus indicating a positive implication in adult neurogenesis. In glial cell populations, like astrocytes, neurotrophins can act through TrkB receptor and affect their reactive state and the subsequent cytokine expression profile. In the present thesis, we investigated the neuroprotective effects of BNN27 and BNN237 initially in P7 hippocampal NSCs. We provide evidence of increased proliferation in these cell populations under extreme stress conditions. We were also able to identify important receptors and downstream signaling pathways implicated in this process. Simultaneously, we begin examining their effects in reactive astrocytes and how these effects can alter the levels of pro- and anti-inflammatory cytokines in the surrounding microenvironment.

Language

English

Subject

DHEA

Microneurotrophins

Μικρονευροτροφίνες

Issue date

2020-12-17

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses

Type of Work--Post-graduate theses

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