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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: Date issued/created: Description:117 pages : illustrations ; 30 cm ; Bibliography ; Summary in English
Degree grantor:Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN
Type of object: Subject and Keywords:Dendritic spine ; Depression ; MMP-9 ; Receptor 5-HT7 ; Synaptic plasticity
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.
Resource type: Detailed Resource Type: Source: Language: Language of abstract: Digitizing institution:Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Original in:Library of the Nencki Institute of Experimental Biology PAS
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