Kordower J H, Mufson E J, Fox N, Martel L, Emerich D F
Research Center for Brain Repair and Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Exp Neurol. 1997 Jun;145(2 Pt 1):586-91. doi: 10.1006/exnr.1997.6492.
The present study determined whether grafts of nerve growth factor-producing fibroblasts alter the expression of beta-amyloid in young or aged nonhuman primates. Aged monkeys serve as an animal model which normally exhibits beta-amyloid-laden plaques. Three young adult (7-12 years of age) and three aged (24-29 years of age) rhesus monkeys received intraventricular implants of polymer-encapsulated cells that were genetically modified to secrete human recombinant nerve growth factor (NGF). Three young adult and three aged rhesus monkeys received identical treatment except that the grafted cells were not genetically modified and thus differed only by a single gene construct. Five additional aged rhesus monkeys were ungrafted and also served as controls. Three to four weeks posttransplantation, young monkeys did not display beta-amyloid-immunoreactive profiles within any CNS structure regardless of treatment. Qualitative observations revealed that aged monkeys displayed numerous beta-amyloid plaque-like structures within the amygdala and hippocampus as well as limbic and neocortices. The amount of beta-amyloid immunoreactivity (beta-amyloid load) was quantified bilaterally within the temporal neocortex of these animals. The beta-amyloid load within the temporal neocortex of aged monkeys was highly variable but did not differ across treatment groups. These data indicate that chronic short-term administration of NGF does not affect the expression of beta-amyloid in the young or the aged primate brain.
本研究确定了产生神经生长因子的成纤维细胞移植是否会改变幼年或老年非人灵长类动物中β-淀粉样蛋白的表达。老年猴子作为一种动物模型，通常会出现富含β-淀粉样蛋白的斑块。三只年轻成年（7 - 12岁）和三只老年（24 - 29岁）恒河猴接受了聚合物包裹细胞的脑室内植入，这些细胞经过基因改造以分泌人重组神经生长因子（NGF）。三只年轻成年和三只老年恒河猴接受了相同的治疗，只是移植的细胞未经过基因改造，因此仅在一个基因构建上有所不同。另外五只老年恒河猴未进行移植，也作为对照。移植后三到四周，无论接受何种治疗，幼年猴子在任何中枢神经系统结构中均未显示出β-淀粉样蛋白免疫反应性特征。定性观察显示，老年猴子在杏仁核、海马以及边缘和新皮质内显示出大量β-淀粉样蛋白斑块样结构。对这些动物颞叶新皮质两侧的β-淀粉样蛋白免疫反应性（β-淀粉样蛋白负荷）进行了定量分析。老年猴子颞叶新皮质内的β-淀粉样蛋白负荷高度可变，但在各治疗组之间没有差异。这些数据表明，长期短期给予NGF不会影响幼年或老年灵长类动物大脑中β-淀粉样蛋白的表达。
