Manuel Narváez Peláez

Title : Galanin and Neuropeptide Y interaction enhances proliferation of granule precursor cells and expression of neuroprotective factors in the rat hippocampus with consequent augmented spatial memory

Abstract:

Dysregulation of hippocampal neurogenesis is linked to several neurodegenereative diseases, 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 neu-rogenic actions on the dorsal hippocampus. We studied the Y1R agonist and GAL effects on: hip-pocampal 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. 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 ob-served on neuronal hippocampal cells. These cellular effects are linked to the improved spa-tial-memory effects after the Y1R agonist and GAL coinjection at 24 hours in the object-in-place task. 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 diseases.

What will audience learn from your presentation?

• Understanding Neuropeptide Y and GAL interaction through Y1R-GALR2 heteroreceptor complex.
• How the the Y1R agonist and GAL may promote cell proliferation in the DG of the dorsal hip-pocampus and the induction of neuroprotective factors, such as BDNF and Bcl-2.
• How Y1R-GALR2 heteroreceptor complexes mediate survival and neurites outgrowth on neuronal hippocampal cells.
• How these cellular effects may be linked to spatial-memory effects.
• 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 diseases.

Biography:

Manuel Narváez cursed Medicine and surgery degree in 2005, with the best academic record of his promotion, in 2006 I obtained a competitive pre-doctoral excellence scholarship from the Andalusian board. The research activity developed allowed him to carry out 5 months visits during 2009 and 2010 at the Karolinska Institute in Stockholm to obtain the European mention. In 2012 I obtained the European PhD thesis with cum laude qualification, the extraordinary PhD award from the faculty of medicine, thesis prize from medical college of Malaga (2012) and the prize from college of pharmacists of Malaga (2013). Up to 6 postdoctoral visits to the Karolinska Institute in Stockholm collaborating on multiple research projects establishing collaborative links with the Swedish research group, during the years 2012-2021, total more than 1 year. 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 impact index in its category and with quality indices, including high cite numbers. Our team has performed multidisciplinary research and worked in a highly integrative manner at different systems levels, we have contributed to the GPCR receptor-receptor interactions field focus in CNS diseases, such as depression, Parkinson, addiction drugs and Alzheimer.