Jetté N, Cole M S, Fahnestock M
Department of Biomedical Sciences, McMaster University, Hamilton, Ont., Canada.
Brain Res Mol Brain Res. 1994 Sep;25(3-4):242-50. doi: 10.1016/0169-328x(94)90159-7.
Alzheimer's disease (AD) is characterized by neuronal dysfunction and degeneration in certain brain regions such as cortex, hippocampus and basal forebrain. Specific neurochemical defects such as decreases in cholinergic enzymes and in the amounts of mRNA in AD brain have also been reported. Nerve growth factor (NGF), a protein necessary for the development, regulation and survival of basal forebrain cholinergic neurons (BFCN), is synthesized in target areas of BFCN (cortex, hippocampus) and is supplied to BFCN by retrograde transport. Thus, NGF is under investigation both as a potential therapeutic agent and for its possible involvement in the pathogenesis of AD. In this study, postmortem brain tissues from both control and AD cases were investigated for amounts of poly (A)+ mRNA and NGF mRNA in the frontal cortex, a region rich in cholinergic afferents. Yields of poly(A)+ mRNA were similar from normal and AD tissues. Human NGF mRNA comigrated with murine NGF mRNA on Northern blots. Additionally, dot blot quantitation demonstrated that NGF mRNA levels do not differ in the inferior frontal gyrus of normal and AD patients. Thus, we conclude that levels of mRNA in general, and of NGF mRNA in particular, are unchanged in the frontal cortex of individuals affected by AD.
阿尔茨海默病(AD)的特征是在某些脑区,如皮质、海马体和基底前脑,出现神经元功能障碍和退化。也有报道称AD大脑存在特定的神经化学缺陷,如胆碱能酶减少和mRNA量减少。神经生长因子(NGF)是基底前脑胆碱能神经元(BFCN)发育、调节和存活所必需的一种蛋白质,在BFCN的靶区域(皮质、海马体)合成,并通过逆向转运供应给BFCN。因此,NGF作为一种潜在的治疗剂以及其可能参与AD发病机制的研究正在进行中。在本研究中,对对照病例和AD病例的死后脑组织进行了研究,以检测额叶皮质(富含胆碱能传入纤维的区域)中多聚(A)+mRNA和NGF mRNA的量。正常组织和AD组织的多聚(A)+mRNA产量相似。在Northern印迹上,人NGF mRNA与小鼠NGF mRNA共迁移。此外,斑点印迹定量显示,正常人和AD患者额下回的NGF mRNA水平没有差异。因此,我们得出结论,在受AD影响的个体的额叶皮质中,一般mRNA水平,特别是NGF mRNA水平没有变化。