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Manuel Narvaez Pelaez , Speaker at Speaker for Pharma 2023
University of Malaga, Spain
Title : Intranasal delivery of Galanin receptor 2 and Neuropeptide Y1 receptor agonists enhances spatial memory and antidepressant effects in rats: Linking to hippocampal neurogenesis.

Abstract:

Dysregulation of hippocampal neurogenesis is linked to several neurodegenereative diseases and depression, 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.

Biography:

Manuel Narvaez Peláez cursed Medicine and surgery with the best academic record of his promotion. Our team has contributed to the GPCR receptor-receptor interactions field focusing in CNS diseases, such as depression, Parkinson's, addiction to drugs and Alzheimer's. As a professor, he is performing an independent and emergent line of research, aim to understand the molecular mechanisms and potential relevance of Y1R heterocomplexes interactions in depression and Alzheimer's disease, in line with my pioneering work in this field. The research results have been published successively in congresses of international and national relevance. In addition, innovative articles have been published, including in the first quartile of the impact index in its category and with quality indices, including high cite numbers. I belong to the CTS-156 of the Junta de Andalucía and the Malaga Biomedical Research Institute (IBIMA). I have reviewed international research projects from CONACYT, Mexico and recently as an evaluator for the Call 'Marie SkÅ‚odowska-Curie Actions Doctoral Networks' (HE-MSCA-DN-2021).

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