Geddes J W, Ułas J, Brunner L C, Choe W, Cotman C W
Division of Neurosurgery, University of California, Irvine 92717.
Neuroscience. 1992 Sep;50(1):23-34. doi: 10.1016/0306-4522(92)90379-g.
Quantitative receptor autoradiography was used to examine the density and distribution of [3H]kainic acid and [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding sites in the hippocampal formation and parahippocampal gyrus obtained at autopsy from 10 Alzheimer's disease and eight normal control individuals. In control and Alzheimer's disease individuals, [3H]kainic acid saturation binding analysis in the outer molecular layer of the dentate gyrus fitted a single-site model. Added calcium ions did not alter the density of [3H]kainic acid binding in the human tissues. These results suggest that calcium-sensitive high-affinity kainic acid binding sites are not present in the human brain in contrast to kainic acid receptors in the rat brain. [3H]AMPA binding was also slightly different in the human brain as compared to the rat, being greatest in the inner third as compared to the outer two-thirds of the dentate gyrus molecular layer. In both control and Alzheimer's disease individuals, [3H]kainic acid and [3H]AMPA binding densities were similar at anterior and posterior levels of the hippocampal formation. In Alzheimer's disease patients, there was a significant increase in [3H]AMPA binding in the infragranular layer. In some, but not all Alzheimer's disease patients, there was an increase in [3H]kainic acid binding densities in the outer half of the dentate gyrus molecular layer. The same individuals which exhibited an increase in [3H]kainic acid binding in the outer molecular layer also displayed increased [3H]AMPA binding in the hilar region. Similar alterations in [3H]kainic acid binding have been observed in rats which had received fimbria-fornix lesions, a model of chronic epilepsy and in individuals with temporal lobe epilepsy. Advanced Alzheimer's disease patients are at risk of developing seizures. The results suggest that several factors including cortical and subcortical pathology and seizure activity may contribute to the alterations in [3H]kainic acid and [3H]AMPA binding observed in the hippocampal formation in Alzheimer's disease.
采用定量受体放射自显影术，检测了10例阿尔茨海默病患者及8例正常对照者尸检获取的海马结构和海马旁回中[3H] kainic酸和[3H]α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）结合位点的密度及分布。在对照者和阿尔茨海默病患者中，齿状回外分子层的[3H] kainic酸饱和结合分析符合单点模型。添加钙离子并未改变人体组织中[3H] kainic酸结合的密度。这些结果表明，与大鼠脑内的kainic酸受体不同，人体大脑中不存在钙敏感的高亲和力kainic酸结合位点。与大鼠相比，人脑内的[3H] AMPA结合也略有不同，在齿状回分子层内三分之一处的结合量最大，而在外三分之二处结合量较小。在对照者和阿尔茨海默病患者中，海马结构前后水平的[3H] kainic酸和[3H] AMPA结合密度相似。在阿尔茨海默病患者中，颗粒下层的[3H] AMPA结合显著增加。在部分（但并非全部）阿尔茨海默病患者中，齿状回分子层外半层的[3H] kainic酸结合密度增加。在齿状回外分子层中表现出[3H] kainic酸结合增加的个体，其海马门区的[3H] AMPA结合也增加。在接受穹窿海马伞损伤的大鼠（一种慢性癫痫模型）以及颞叶癫痫患者中，也观察到了类似的[3H] kainic酸结合改变。晚期阿尔茨海默病患者有发生癫痫发作的风险。结果表明，包括皮质和皮质下病理改变以及癫痫活动在内的多种因素，可能导致了阿尔茨海默病患者海马结构中观察到的[3H] kainic酸和[3H] AMPA结合改变。
