On the Role of Neuropeptide Y Receptor 1 (NPY1R)-Galanin Receptor 2 (GALR2) Heteroreceptor Complexes in Enhancing Adult Hippocampal Neurogenesis and Cognitive Function

Abstract

This PhD thesis investigates the roles of Neuropeptide Y receptor 1 (NPY1R) homo- and heteroreceptor complexes, specifically NPY1R- galanin receptor 2 (GALR2) heteroreceptor complexes, within the Central Nervous System (CNS), focusing on hippocampal neuronal cells and their implications for neurogenesis, mood regulation, and cognitive functions. These receptor complexes introduce a novel dimension to molecular neuroscience, as allosteric receptor-receptor interactions can modify receptor function, signaling pathways, and pharmacological responses. The research explores how these complexes influence hippocampal neurogenesis and cognition under physiological and pathological conditions, with two primary objectives. First, the study aims to examine whether intranasal administration of GALR2 and NPY1R agonists stimulates adult neurogenesis in the ventral hippocampus and induces antidepressant-like effects. By analyzing the activation of the ventral hippocampus through c-Fos and PCNA expression and the formation of NPY1R-GALR2 heteroreceptor complexes using in situ proximity ligation assays (PLA), the research highlights increased cell proliferation, particularly in neuroblasts, without affecting quiescent progenitors or astrocytes. The study reveals that these effects are mediated by increased BDNF expression, a crucial neurotrophic factor involved in neurogenesis and mood regulation.