Brady D R, Mufson E J
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, U.S.A.
Neuroscience. 1997 Oct;80(4):1113-25. doi: 10.1016/s0306-4522(97)00068-7.
The number and topographic distribution of immunocytochemically stained parvalbumin interneurons was determined in the hippocampal formation of control and Alzheimer's diseased brain. In control hippocampus, parvalbumin interneurons were aspiny and pleomorphic, with extensive dendritic arbors. In dentate gyrus, parvalbumin cells, as well as a dense plexus of fibers and puncta, were associated with the granule cell layer. A few cells also occupied the molecular layer. In strata oriens and pyramidale of CA1-CA3 subfields, parvalbumin neurons gave rise to dendrites that extended into adjacent strata. Densely stained puncta and beaded fibers occupied stratum pyramidale, with less dense staining in adjacent strata oriens and radiatum. Virtually no parvalbumin profiles were observed in stratum lacunosum-moleculare or the alveus. Numerous polymorphic parvalbumin neurons and a dense plexus of fibers and puncta characterized the deep layer of the subiculum and the lamina principalis externa of the presubiculum. In Alzheimer's diseased hippocampus, there was an approximate 60% decrease in the number of parvalbumin interneurons in the dentate gyrus/CA4 subfield (P<0.01) and subfields CA1-CA2 (P<0.01). In contrast, parvalbumin neurons did not statistically decline in subfields CA3, subiculum or presubiculum in Alzheimer's diseased brains relative to controls. Concurrent staining with Thioflavin-S histochemistry did not reveal degenerative changes within parvalbumin-stained profiles. These findings reveal that parvalbumin interneurons within specific hippocampal subfields are selectively vulnerable in Alzheimer's disease. This vulnerability may be related to their differential connectivity, e.g., those regions connectionally related to the cerebral cortex (dentate gyrus and CA1) are more vulnerable than those regions connectionally related to subcortical loci (subiculum and presubiculum).
在对照和阿尔茨海默病大脑的海马结构中,确定了免疫细胞化学染色的小白蛋白中间神经元的数量和拓扑分布。在对照海马中,小白蛋白中间神经元无棘且形态多样,具有广泛的树突分支。在齿状回中,小白蛋白细胞以及密集的纤维丛和斑点与颗粒细胞层相关。少数细胞也占据分子层。在CA1 - CA3亚区的海马伞和锥体层中,小白蛋白神经元产生延伸至相邻层的树突。密集染色的斑点和串珠状纤维占据锥体层,相邻的海马伞层和辐射层染色较淡。在腔隙-分子层或海马槽中几乎未观察到小白蛋白形态。大量多形性小白蛋白神经元以及密集的纤维丛和斑点是海马下托深层和前海马下托外侧主层的特征。在阿尔茨海默病海马中,齿状回/CA4亚区(P<0.01)和CA1 - CA2亚区(P<0.01)的小白蛋白中间神经元数量减少了约60%。相比之下,与对照相比,阿尔茨海默病大脑中CA3亚区、海马下托或前海马下托的小白蛋白神经元数量在统计学上没有下降。硫黄素-S组织化学的同时染色未显示小白蛋白染色形态内的退行性变化。这些发现表明,特定海马亚区内的小白蛋白中间神经元在阿尔茨海默病中具有选择性易损性。这种易损性可能与其不同的连接性有关,例如,那些与大脑皮层连接相关的区域(齿状回和CA1)比那些与皮层下位点连接相关的区域(海马下托和前海马下托)更易受损。