NEUROPROTECTIVE EFFECTS OF VEGF-B IN A MODEL OF SELECTIVE AND LATE NEURONAL DEATH

Neurodegenerative diseases represent a major challenge and require substantial economic investment in both social and healthcare systems. Our group has extensive experience in the analysis of an animal model used to develop neuroprotective strategies, the PCD mouse, which suffers neuronal death affecting the olfactory bulb (OB). Such degeneration mimics some of the most prevalent features of human neurodegenerative processes, as it is late-onset and prolonged over time. Here, we aimed at demonstrating the neuroprotective properties of Vascular Endothelial Growth Factor type B (VEGF-B). Specifically, we investigated whether systemic administration of this neurotrophic factor could reduce neuronal death in the OB of PCD mice. To this end, two different schedules of periodic intraperitoneal VEGF-B administration were performed: from postnatal day 40 (P40) to P90 or from P50 to P90, with injections every five days. Animals underwent olfactory behavioural tests and were subsequently sacrificed for immunofluorescence analysis of the OB. Preliminary results suggest that VEGF-B increases mitral cell survival in PCD mice, as evidenced by an increase in neuronal number, soma size, and dendritic trunk diameter. These morphological changes may be reflected in improved olfactory capabilities. In addition, the density of vascular endothelial growth factor receptor 1 (VEGFR1) in mitral cells shows an opposite distribution, with higher expression in untreated PCD mice. Overall, these findings represent a further step toward the development of effective neuroprotective therapy using VEGF-B. Moreover, we are now developing new systems of VEGF-B though its overexpression in transplanted bone marrow stem cells.