Title : Stem cell-induced proliferation on the hippocampus after intranasal administration of Galanin receptor 2 and neuropeptide Y1 receptor agonists: Role in spatial memory and depression-like effects in rats
Abstract:
Several neurodegenereative diseases and depression are linked to dysregulation of hippocampal neurogenesis, where boosting hippocampal neurogenesis in these patients emerges as a potential therapeutic approach. Accumulating evidence for Neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-, cellular- and behavioral-specific levels. The purpose of the current work was to evaluate the role of NPY and GAL interaction in the neurogenic actions on the dorsal and ventral hippocampus. We studied the Y1R agonist and GAL effects on: hippocampal cell proliferation through the proliferating cell nuclear antigen (PCNA); the expression of neuroprotective and anti-apoptotic factors and the survival of neurons and neurite outgrowth on hippocampal neuronal cells. The functional outcome was evaluated in the object-in-Place task and the forced swimming test. We demonstrated that the Y1R agonist and GAL and promote cell proliferation and the induction of neuroprotective factors. These effects were mediated by the interaction of NPYY1 (Y1R) and GAL2 (GALR2) receptors, which mediate the increased survival and neurites outgrowth observed on neuronal hippocampal cells. These cellular effects are linked to the improved spatial-memory effects after the Y1R agonist and GAL coinjection at 24 hours in the object-in-place task and in the forced swimming test. Our results suggest the development of heterobivalent agonist pharmacophores, targeting Y1R-GALR2 heterocomplexes, therefore acting on the neuronal precursor cells of the DG in the dorsal hippocampus for the novel therapy of neurodegenerative cognitive-affecting and depressive diseases.
