Institutional creator:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Contributor:

Kalita-Bykowska, Katarzyna : Supervisor

Publisher:

Instytut Biologii Doświadczalnej im. M. Nenckiego PAN

Place of publishing:

Warszawa

Description:

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

Degree grantor:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Type of object:

Thesis

Abstract:

The transmission of information between neurons in the central nervous system (CNS) occurs mainly at synapses. The postsynaptic part of most excitatory synapses in the brain is located at dendritic spines, which are small membranous protrusions of nerve cells. Dendritic spines are highly dynamic structures, undergoing structural and functional plasticity. Changes in the dendritic spine shape correlate with the degree of maturation of synapses and the strength of neuronal connections. The proper synapse function is crucial for effective memory and learning. Furthermore, abnormalities in the maturation process or in the number of dendritic spines are frequently observed in the clinical picture of different neurodevelopmental diseases such as autism spectrum disorders, fragile X syndrome or Rett syndrome. Formation and maturation of dendritic spines is a very complex phenomenon, and despite numerous studies, the molecular mechanisms underlying the processes of synapse formation, and development are still not fully understood. Recent analyses have shown a correlation between the occurrence of certain neurodevelopmental disorders in humans and point mutations within genes whose expression is regulated by Serum Response Factor (SRF) or its cofactors. SRF protein is a transcription factor significantly involved in both physiological and pathological processes occurring in neurons. SRF regulates long-term potentiation (LTP), long-term depression (LTD), neuronal activity-dependent gene expression, neuronal network formation or epileptogenesis. SRF activity is controlled by its coactivators including myocardin-related transcription factors, MRTF. Moreover, there is also a relationship between single nucleotide mutations within mrtf genes, and the occurrence of autism spectrum disorders or schizophrenia. Until now, the role of SRF protein and its coactivators on the process of dendritic spine formation and maturation was unknown. The results presented herein showed that SRF or MRTF regulates dendritic spike maturation and synapse function in developing neurons. Silencing SRF expression in vitro and in vivo impaired dendritic spine structure and increased the number of immature spines with no apparent changes in their overall density. Moreover, downregulation of MRTF protein had a similar effect on dendritic spike morphology as SRF depletion. Additionally, the observed structural changes were

Detailed Resource Type:

PhD Dissertations

Resource Identifier:

oai:rcin.org.pl:236540

Source:

IBD PAN, call no. 20077

Language:

pol

Language of abstract:

eng

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