Title:Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer's Disease After Implantation of VEGF-loaded PLGA Nanospheres
VOLUME: 12 ISSUE: 10
Author(s):E. Herran, R. Perez- Gonzalez, M. Igartua, J.L. Pedraz, E. Carro and R.M. Hernandez
Affiliation:Neuroscience Laboratory, Research Center, Hospital Universitario 12 de Octubre, Spain.
Keywords:Alzheimer’s disease, APP/Ps1, Nanospheres, neurogenesis, PLGA, VEGF.
Abstract:During adult life, hippocampus is an important brain region involved in neurogenesis. The
generation and cell death of newly generated neuronal cells in this region have critical roles in brain
maintenance and alterations in these processes are seen in Alzheimer’s disease (AD). For the purpose
of carrying out a neuroregenerative strategy, we propose a novel approach based on the encapsulation
of vascular endothelial growth factor (VEGF) in poly (lactic co-glycolic acid) (PLGA) biodegradable nanospheres (NS)
administered by craniotomy to stimulate the proliferation of neuronal precursors in a transgenic mouse model of AD.
VEGF loaded nanospheres were prepared by double emulsion solvent evaporation technique, obtaining 200 nm nanospheres
with a biphasic release profile. After demonstrating their efficacy in the proliferation and differentiation of neuronal
cell cultures, in vivo studies were carried out. 3 months after VEGF-NS were implanted directly into the cerebral
cortex of APP/Ps1 mice, the determination of BrdU+ cells in the whole hippocampal region and specifically in the dentate
gyrus, demonstrated a significantly enhanced cellular proliferation in VEGF-NS treated group. These results were also
confirmed showing an increased number of DCX+ and NeuN+ cells. Hence, PLGA-VEGF nanospheres may be a potential
strategy to modulate proliferative neuronal progenitors in the hippocampal region, and therefore, provide new insight for
future therapeutic approaches in AD.
