Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer's Disease After Implantation of VEGF-loaded PLGA Nanospheres
Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer's Disease After Implantation of VEGF-loaded PLGA Nanospheres
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DOI：
10.2174/1567205012666151027121622
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发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Hernandez, R. M.
中科院分区：
文献类型：
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作者：
Herran, E.;Perez-Gonzalez, R.;Hernandez, R. M.
在成年期，海马是参与神经发生的重要脑区。在这个区域中新产生的神经元细胞的产生和细胞死亡在脑维持中具有关键作用，并且在阿尔茨海默病（AD）中观察到这些过程中的改变。为了进行神经再生策略的目的，我们提出了一种新的方法的基础上封装的血管内皮生长因子（VEGF）在聚（乳酸共-乙醇酸）（PLGA）可生物降解的纳米球（NS）通过开颅手术给药，以刺激AD的转基因小鼠模型中的神经元前体细胞的增殖。通过复乳溶剂蒸发技术制备负载VEGF的纳米球，获得具有双相释放曲线的200 nm纳米球。在证明它们在神经元细胞培养物的增殖和分化中的功效后，进行了体内研究。将VEGF-NS直接植入APP/Ps1小鼠大脑皮层3个月后，对整个海马区，特别是齿状回BrdU（+）细胞的测定表明，VEGF-NS治疗组的细胞增殖显著增强。这些结果也得到证实，显示DCX+和NeuN（+）细胞数量增加。因此，PLGA-VEGF纳米球可能是调节海马区增殖神经元祖细胞的潜在策略，因此，为AD的未来治疗方法提供了新的见解。
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.