Joyce J N, Myers A J, Gurevich E
Christopher Parkinson's Disease Research Center, Sun Health Research Institute, Sun City, AZ, 85372, USA.
Brain Res. 1998 Feb 16;784(1-2):7-17. doi: 10.1016/s0006-8993(97)01005-6.
A modular organization of bands enriched in high concentrations of D2 receptors are observed throughout the rostral to caudal aspects of the temporal cortex of the normal human at postmortem, but are most frequently observed in the inferior and superior temporal cortices [S. Goldsmith, J.N. Joyce, Dopamine D2 receptors are organized in bands in normal human temporal cortex, Neuroscience 74 (1996) 435-451]. In the tissue derived at postmortem from Alzheimer's disease cases (AD), these D2 receptor-enriched modules were found to be largely absent at rostral and mid-levels of the temporal cortex. Regions exhibiting this loss of receptor binding also showed a marked reduction in the number of pyramidal neurons stained for D2 mRNA. In addition, the AD material exhibited numerous thioflavin-positive plaques and tangle-filled extraneuronal (ghost) pyramidal neurons that were D2 mRNA-negative. Regions that are the earliest affected and most susceptible to classical AD pathology are also most sensitive to the loss of D2 receptors. These results, along with our previous data [J.N. Joyce, C. Kaeger, H. Ryoo, S. Goldsmith, Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease, Neurosci. Lett. 154 (1993) 171-174; H. Ryoo, J. N. Joyce, The loss of dopamine D2 receptors varies along the rostrocaudal axis of the hippocampal complex in Alzheimer's disease, J. Comp. Neurol. 348 (1994) 94-110], indicate that specific pathways enriched with D2 receptors, including that within modules of higher order association cortices of the temporal lobe and continued through segregated pathways within the parahippocampus and hippocampus, are particularly susceptible to the loss in AD. These dopamine D2 receptor-enriched modules may play an important role in the reciprocal activity of large groups of neurons in these high-order association cortical regions. Hence, the loss of the D2 receptor-enriched modules in Alzheimer's disease contributes to disturbances in information processing in these high-order association cortices, and may promote the cognitive and non-cognitive impairments observed in Alzheimer's disease.
在正常人类尸检时，从颞叶皮质的嘴侧到尾侧均观察到富含高浓度D2受体的条带呈模块化组织，但在颞下回和颞上回中最为常见[S. 戈德史密斯、J.N. 乔伊斯，多巴胺D2受体在正常人类颞叶皮质中呈条带状组织，《神经科学》74 (1996) 435 - 451]。在阿尔茨海默病（AD）患者尸检获得的组织中，发现在颞叶皮质的嘴侧和中间水平，这些富含D2受体的模块大多缺失。显示受体结合丧失的区域，D2 mRNA染色的锥体神经元数量也显著减少。此外，AD组织中有大量硫黄素阳性斑块和充满缠结的神经元外（幽灵）锥体神经元，这些神经元D2 mRNA呈阴性。最早受影响且最易患典型AD病理改变的区域，对D2受体丧失也最为敏感。这些结果，连同我们之前的数据[J.N. 乔伊斯、C. 凯格、H. 柳、S. 戈德史密斯，阿尔茨海默病中海马体和杏仁核中的多巴胺D2受体，《神经科学快报》154 (1993) 171 - 174；H. 柳、J.N. 乔伊斯，阿尔茨海默病中多巴胺D2受体丧失沿海马复合体的嘴尾轴变化，《比较神经学杂志》348 (1994) 94 - 110]表明，富含D2受体的特定通路，包括颞叶高阶联合皮质模块内的通路，并通过海马旁回和海马内的分离通路延续，在AD中特别容易丧失。这些富含多巴胺D2受体的模块可能在这些高阶联合皮质区域的大量神经元的相互活动中起重要作用。因此，阿尔茨海默病中富含D2受体模块的丧失导致这些高阶联合皮质中信息处理的紊乱，并可能促进阿尔茨海默病中观察到的认知和非认知障碍。
