Różnice w plastyczności synaptycznej w podregionach hipokampu zależne od receptora 5-HT7 : praca doktorska

Masternak, Julia

Skip to main menu
Skip to search engine
Skip to content
Skip to footer

Różnice w plastyczności synaptycznej w podregionach hipokampu zależne od receptora 5-HT7 : praca doktorska

Download

Description
Information

Title: Różnice w plastyczności synaptycznej w podregionach hipokampu zależne od receptora 5-HT7 : praca doktorska

Abstract:

The World Health Organization estimates that 5% of adults all over the world suffer from major depression disorder (MDD). The most important symptoms of MDD are feeling sadness, irritation, emptiness, loss of interest and happiness, low self-esteem and chronic fatigue. They are not very always noticed and people suffering from depression can often hide them well. In extreme cases, untreated or ineffectively treated depression can lead to suicidal thoughts or even suicide attempts. The main studies related to this issue are based on understanding of the molecular mechanisms leading to depression. Among multiple serotonin receptors involved in this disorder, serotonin receptor 7 (5-HT7R) has recently raised considerable interest. Depression is now thought to result from structural changes in specific areas of the brain. Numerous neurological and neuropsychiatric diseases (including depression) contribute to abnormalities in the density and shape of small protuberances on the dendrites (dendritic spines). The shape of dendritic spines usually correlates with their function and the physiological strength of the synaptic connection. The discovery of the exact mechanisms modulating spines shape is extremely important and may represent a breakthrough in the treatment of depression. Morphometric analysis of dendritic spines has shown that activation of 5-HT7R leads to the elongation of dendritic spines in CA1, while spines maturation was observed in the DG subregion. These changes were also shown to be transient. Using a combination of biochemical and biophysical methods, a detailed investigation of the mechanisms underlying CA1- and DG- specific differences in structural plasticity following 5-HT7R stimulation was conducted. The activation profiles of the key regulators of the actin cytoskeleton, the Cdc42 and RhoA proteins, were examined in hippocampal subregions. Differential effects of 5-HT7R agonists on the shape and density of dendritic spines, as well as on animal behaviour, have been demonstrated. This study confirms the crucial and multidimensional involvement of 5-HT7R activation in modulating structural plasticity in the hippocampus.