Abstract |
The κ- opioid system, composed of the κ- opioid receptor (κ-OR) and its endogenous ligand dynorphin, is widely expressed in the CNS. Apart from pain perception and analgesia, the κ- opioid system is implicated in the manifestation and treatment of several diseases, such as anxiety and depression disorders, drug addiction and epilepsy. Moreover, activation of the κ-OR directly regulates neurotransmission and synaptic plasticity in key brain regions, such as the cortex, the hippocampus, the ventral striatum and several midbrain structures, however the molecular mechanisms that serve these functions are not well characterized. Recent observations from Dr. Georgoussi lab indicate that activation of the κ-OR by the specific agonist U50,488H induces autophagy in the neuroblastoma Neuro2A cell line (unpublished data). Autophagy is a dynamic and tightly regulated multistep procedure, responsible for the degradation of malfunctioning or superfluous proteins, macromolecules and organelles in order to maintain cellular homeostasis and quality control. The aim of this master thesis was to examine the interplay between κ-OR activation and autophagy in the nervous system, under physiological conditions. Our results demonstrate that activation of κ-OR can induce autophagy in a dose and time dependent manner in vitro in primary neuronal cultures and upregulate de novo autophagosomal biogenesis. Moreover, our preliminary data support that activation of κ-OR in vivo differentially regulates autophagy in the mouse cortex, hippocampus and striatum. These findings will be the starting point of my PhD study, where we intent to further investigate the role of κ-OR induced autophagy in vivo and access its involvement in physiology and behavior.
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