Johnson S A, Lampert-Etchells M, Pasinetti G M, Rozovsky I, Finch C E
Neurogerontology Division, Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Neurobiol Aging. 1992 Nov-Dec;13(6):641-8. doi: 10.1016/0197-4580(92)90086-d.
This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.
本研究描述了在成年人类和大鼠大脑中存在编码两种补体（C）蛋白C1qB和C4的mRNA的证据。C蛋白是外周组织中体液免疫和炎症的重要效应因子，但以往未被认为正常存在于大脑中。先前的免疫细胞化学研究表明，C蛋白与阿尔茨海默病（AD）中的斑块、缠结和营养不良性神经突有关，但其来源尚不清楚。免疫细胞化学和原位杂交技术相结合显示，锥体神经元中有C4 mRNA，小胶质细胞中有C1qB mRNA。原代大鼠神经元培养物中也显示有C1qB mRNA。在AD大脑的皮质中，C1qB mRNA和C4 mRNA增加了两到三倍，C1qB mRNA患病率的增加部分与小胶质细胞有关。作为AD的模型，我们检查了大鼠大脑内嗅皮质穿通通路横断，这导致同侧海马体和内嗅皮质中C1qB mRNA迅速增加，而对侧则没有。现在可以结合与细胞变性和/或细胞保存及突触可塑性相关的C蛋白功能，来考虑AD和实验性损伤期间大脑源性急性和慢性C诱导的作用。
