In vivo characterization of the interaction between angiotensin fragments and the central neurotransmitter systems

Besides the well-known renin-angiotensin system (RAS) in the kidney, there exists a RAS in the brain. This central system also regulates blood pressure, but other functions such as motor control, learning and memory have been proposed. The main peptide of the RAS is angiotensin II (Ang II), that exerts its effects via AT1 and AT2 receptors. Recently, fragments of Ang II, such as Ang IV and Ang (1-7) have been suggested to influence the RAS and to have specific functions in the brain. Indeed, central Ang II influences the dopaminergic system of the basal ganglia, which may explain the role of Ang II in motor control and its link with pathologies such as Parkinsons and Huntingtons disease. Ang II and Ang IV, have been suggested to play a role in hippocampal physiology and epilepsy since they modulate the glutamatergic and GABA-ergic system. A role of these peptides in cognition has been explained by a Ang IV-acetylcholine interaction.
However, only few in vivo data exist explaining the effects of these peptides in the brain. In this project we will study the effects of Ang II, and its fragments Ang IV and Ang (1-7) on the neurotransmitter release (noradrenaline, dopamine, serotinine, glutamate, GABA and acetylcholine) in the striatum, hippocampus and prefrontal cortex of the freely moving rat using in vivo microdialysis. This fundamental study will allow us to characterize the interaction between these Ang peptides and different neurotransmittersystems in vivo. In a second step, the observed effects will be linked to different disease states. The fragments will be studied in animal models for certain pathologies, such as Parkinsons disease and epilepsy, already developed in the laboratory and characterized by changes in neurotransmitter release.