Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand.
Neurochem Res. 2012 Jan;37(1):143-52. doi: 10.1007/s11064-011-0592-1. Epub 2011 Sep 11.
Alzheimer's disease (AD) is characterized by the depositions of amyloid-β (Aβ) proteins, resulting in a reduction of choline acetyltransferase (ChAT) activity of AD brain in the early stages of the disease. Several growth factors, including brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF)-1 and glial cell-derived neurotrophic factor (GDNF) are known to protect neuronal cell death in several neurodegenerative both in vitro and in vivo models. In this study, septal neurons were prepared from septal nucleus of embryonic (day 16-17) rat brain and treated with monomeric, oligomeric or fibrillar Aβ(1-42) peptide. Oligomeric Aβ(1-42), (10 μM) was the most potent at sublethal dose. Septal neuron cultures treated with BDNF, IGF-1 or GDNF or co-cultured with genetically modified human neural progenitor cells (hNPCs) secreting these neurotrophic factors (but not allowing contact between the two cell types), were protected from oligomeric Aβ(1-42) peptide-induced cell death, and these trophic factors enhanced cholinergic functions by increasing ChAT expression level. These results indicate the potential of employing transplanted hNPCs for treatment of AD.
阿尔茨海默病（AD）的特征是淀粉样蛋白-β（Aβ）蛋白的沉积，导致 AD 大脑中的胆碱乙酰转移酶（ChAT）活性在疾病的早期阶段降低。几种生长因子，包括脑源性神经营养因子（BDNF）、胰岛素样生长因子（IGF）-1 和胶质细胞源性神经营养因子（GDNF），已知可在体外和体内模型中保护神经元细胞死亡，包括几种神经退行性疾病。在这项研究中，从胚胎（第 16-17 天）大鼠脑的隔核中制备隔神经元，并将其与单体、寡聚体或纤维状 Aβ（1-42）肽一起处理。寡聚体 Aβ（1-42）（10 μM）在亚致死剂量下最有效。用 BDNF、IGF-1 或 GDNF 处理的隔神经元培养物或与遗传修饰的人神经祖细胞（hNPC）共培养，这些 hNPC 分泌这些神经营养因子（但不允许两种细胞类型之间接触），可防止寡聚体 Aβ（1-42）肽诱导的细胞死亡，这些营养因子通过增加 ChAT 表达水平增强了胆碱能功能。这些结果表明，移植 hNPC 用于治疗 AD 的潜力。
