VEGF加载在纳米粒中增强APP/PS1阿尔茨海默病模型小鼠海马神经发生

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:

关键词: 阿尔茨海默病，APP/PS1，纳米微球，神经，PLGA，VEGF。

摘要: 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.

Cite this article as:

E. Herran, R. Perez- Gonzalez, M. Igartua, J.L. Pedraz, E. Carro and R.M. Hernandez , Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer's Disease After Implantation of VEGF-loaded PLGA Nanospheres, Current Alzheimer Research 2015; 12 (10) . https://dx.doi.org/10.2174/1567205012666151027121622