Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Anichstr. 35, A-6020 Innsbruck Medical University, Austria.
Brain Res. 2010 Feb 2;1312:108-19. doi: 10.1016/j.brainres.2009.11.062. Epub 2009 Dec 11.
Alzheimer's disease is an age-dependent brain disorder, characterized by progressive memory deficits and cognitive decline and loss of cholinergic neurons. Nerve growth factor (NGF) is the most potent protein to protect cholinergic neurons against degeneration. However, problems of delivery to the brain limit the therapeutical use of NGF. The aim of the present study was to test, if primary rat monocytes can be loaded with recombinant NGF and pass an in vitro monolayer of brain capillary endothelial cells (BCEC), release NGF, and support the cholinergic neurons in an organotypic brain slice model. Monocytes were isolated from rat blood by negative magnetic selection, loaded with recombinant NGF using Bioporter. The monocytes adhered and migrated through an in vitro rat BCEC-monolayer. NGF released at the basolateral side counteracted degeneration of cholinergic basal nucleus of Meynert neurons. In conclusion, our present study shows a proof-of-principle, that primary monocytes secreting NGF might be useful tools to deliver NGF into the brain, however, further in vivo studies are necessary.
阿尔茨海默病是一种与年龄相关的脑疾病，其特征是进行性记忆缺失、认知能力下降和胆碱能神经元丧失。神经生长因子（NGF）是保护胆碱能神经元免受退化的最有效蛋白。然而，向大脑输送的问题限制了 NGF 的治疗用途。本研究的目的是测试原代大鼠单核细胞是否可以负载重组 NGF 并通过体外脑毛细血管内皮细胞（BCEC）单层释放 NGF，并在器官型脑切片模型中支持胆碱能神经元。单核细胞通过负磁选择从大鼠血液中分离出来，使用 Bioporter 负载重组 NGF。单核细胞在体外大鼠 BCEC 单层上黏附和迁移。在基底外侧释放的 NGF 对抗胆碱能基底核 Meynert 神经元的退化。总之，本研究证明了一个原理，即分泌 NGF 的原代单核细胞可能是将 NGF 递送到大脑的有用工具，但是还需要进一步的体内研究。
