Kordower J H, Winn S R, Liu Y T, Mufson E J, Sladek J R, Hammang J P, Baetge E E, Emerich D F
Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10898-902. doi: 10.1073/pnas.91.23.10898.
Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricular transplants of polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reductions in the number of choline acetyltransferase- (57-75%) and p75 NGF receptor- (53%) immunoreactive medial septal neurons ipsilateral to the lesion/implant. In contrast, monkeys receiving transplants of encapsulated hNGF-secreting cells display only a modest loss of choline acetyltransferase- (0-36%) and p75 NGF receptor-(7-22.4%) immunoreactive septal neurons. Additionally, all monkeys receiving the hNGF-secreting implants, but none receiving control implants, displayed robust sprouting of cholinergic fibers within the septum ipsilateral to the transplant. Just prior to sacrifice, the capsules were retrieved and found to contain viable BHK cells releasing biologically relevant levels of hNGF. These data demonstrate that hNGF can provide trophic and tropic influences to aged primate basal forebrain neurons undergoing lesion-induced degeneration, supporting the contention that hNGF may prevent the degeneration of basal forebrain neurons in Alzheimer disease.
6只年龄在24至29岁之间的恒河猴接受了穹窿单侧横断手术。然后，3只猴子接受了聚合物包裹的经基因改造以分泌人神经生长因子（hNGF）的幼仓鼠肾（BHK）成纤维细胞的脑室内移植。其余3只猴子接受了相同的移植，但细胞未被改造以分泌hNGF。接受穹窿横断和对照移植的猴子，其损伤/植入同侧的胆碱乙酰转移酶免疫反应性（57 - 75%）和p75神经生长因子受体免疫反应性（53%）内侧隔区神经元数量大幅减少。相比之下，接受包裹的分泌hNGF细胞移植的猴子，胆碱乙酰转移酶免疫反应性（0 - 36%）和p75神经生长因子受体免疫反应性（7 - 22.4%）的隔区神经元仅出现适度损失。此外，所有接受分泌hNGF植入物的猴子，但接受对照植入物的猴子均未出现，在移植同侧的隔区内显示出胆碱能纤维的强劲发芽。在处死前，取出胶囊，发现其中含有释放生物学相关水平hNGF的活BHK细胞。这些数据表明，hNGF可以对经历损伤诱导退变的老年灵长类基底前脑神经元提供营养和向性影响，支持了hNGF可能预防阿尔茨海默病中基底前脑神经元退变的观点。
