Institutional creator:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Contributor:

Włodarczyk, Jakub : Supervisor ; Bijata, Monika : Assistant supervisor

Publisher:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Place of publishing:

Warszawa

Description:

117 pages : illustrations ; 30 cm ; Bibliography ; Summary in English

Degree name:

PhD in Biological Sciences

Degree discipline :

Biological Sciences

Degree grantor:

Nencki Institute of Experimental Biology PAS ; degree obtained: 14.04.2023

Type of object:

Thesis

Abstract:

Depression is a global medical problem frequently leading to suicides. It is assumed that depressive symptoms occur as a result of aberrant excitatory synaptic plasticity developed after chronic stress. Synaptic plasticity is an ability of neurons to modulate the strength of synaptic connections manifested by structural alterations of dendritic spines on which excitatory synapses are located. Recently discovered activation of the serotonin type 7 receptor (5-HT7R)-dependent signaling pathway leads to aberrant structural and functional synaptic plasticity in the hippocampal neurons in vitro. However, whether this signaling pathway exists in vivo or not and what its role is, it has not yet been investigated.Using a combination of behavioral, biochemical, and imaging methods, it has been demonstrated that the 5-HT7R-dependent signaling pathway is activated in the murine hippocampus and underlies the depressive-like phenotype. Additionally, the results confirmed that the activation of the 5-HT7R-dependent signaling pathway is associated with the structural remodeling of dendritic spines of anhedonic animals. The stress-resilient animals did not display the aforementioned biochemical and structural alterations indicating the specificity of the obtained results. Moreover, the implementation of the chronic unpredictable stress procedure with specific silencing of htr7 gene expression in the CA1 hippocampal subregion enabled to discover that silencing of 5-HT7R in the hippocampus is sufficient to prevent the development of anhedonia.The obtained results point out a crucial role of 5-HT7R in the pathogenesis of depressive-like behavior and the dendritic spine structure as a possible decisive molecular target for promoting stress resilience in future pharmacotherapies.

Detailed Resource Type:

PhD Dissertations

Resource Identifier:

oai:rcin.org.pl:238068

Source:

IBD PAN, call no. 20185

Language:

pol

Language of abstract:

eng

Rights:

Rights Reserved - Free Access

Terms of use:

Copyright-protected material. May be used within the limits of statutory user freedoms

Copyright holder:

Publication made available with the written permission of the author

Digitizing institution:

Nencki Institute of Experimental Biology of the Polish Academy of Sciences

Original in:

Library of the Nencki Institute of Experimental Biology PAS

Access:

Open