Pauwels P J, van Assouw H P, De Ryck M, Leysen J E, Dom R, Van Gool D
Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Brain Res. 1993 Apr 30;610(1):8-15. doi: 10.1016/0006-8993(93)91210-j.
Neuronal cell survival was investigated in rat brain cortical cultures in the presence of increasing concentrations of human brain extracts or cerebrospinal fluid (CSF) from control and Senile Dementia of Alzheimer's type (SDAT) patients. Using hippocampal brain extracts, converted 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was compared to the content of the neuronal marker MAP2 in foetal rat brain neuronal cultures in order to test converted MTT as a quantitative parameter for neuronal cell survival. A significant correlation was found between both parameters. SDAT frontal cortex brain extracts induced a two four-fold increase in neuronal cell survival at 25 to 125 micrograms protein extract, whereas control brain extracts induced at similar protein concentrations a decline in neuronal cell survival. The enhanced survival yielded by SDAT brain extracts was fully abolished in the presence of control brain extract. Control CSF concentration-dependently increased neuronal cell survival in postnatal rat brain neuronal cultures independent of the difference in the protein content of CSF samples and age of the patients. SDAT CSF also concentration-dependently enhanced neuronal cell survival, however, the effect was more pronounced compared to control CSF. These observations are in favour of the hypothesis that there might be a higher neurotrophic activity in SDAT brain tissue.
在含有浓度不断增加的人脑提取物或来自对照及阿尔茨海默病型老年痴呆(SDAT)患者脑脊液(CSF)的大鼠脑皮质培养物中,对神经元细胞存活情况进行了研究。使用海马脑提取物,将转化的3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑(MTT)与胎鼠脑神经元培养物中神经元标志物微管相关蛋白2(MAP2)的含量进行比较,以测试转化的MTT作为神经元细胞存活的定量参数。发现这两个参数之间存在显著相关性。SDAT额叶皮质脑提取物在蛋白提取物浓度为25至125微克时可使神经元细胞存活增加两到四倍,而对照脑提取物在相似蛋白浓度下则导致神经元细胞存活下降。在对照脑提取物存在的情况下,SDAT脑提取物所产生的存活增强效应完全被消除。对照CSF在新生大鼠脑神经元培养物中浓度依赖性地增加神经元细胞存活,与CSF样本的蛋白含量及患者年龄的差异无关。SDAT CSF也浓度依赖性地增强神经元细胞存活,然而,与对照CSF相比,这种效应更为明显。这些观察结果支持这样一种假说,即SDAT脑组织中可能存在更高的神经营养活性。