Strain S M, Tasker R A
Department of Anatomy & Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
Neuroscience. 1991;44(2):343-52. doi: 10.1016/0306-4522(91)90059-w.
The effect of systemic administration of domoic acid, a potent structural analogue of kainic acid, on the mouse hippocampus has been studied using light and electron microscopic techniques. Intraperitoneal injections of either domoic acid (4 mg/kg) or kainic acid (32 mg/kg) produced a series of behavioural changes including sedation, rigidity, stereotypy (scratching, head nodding), balance loss, and discrete or generalized convulsions. Both qualitative and quantitative histological analysis revealed similar but not identical patterns of neuronal damage in the hippocampal formation of domoic acid- and kainic acid-treated mice. With both toxins the most extensive damage was always observed in the CA3 region of the hippocampus, with lesser degrees of damage observed in other hippocampal regions (CA4 greater than CA1 greater than CA2 greater than dentate granule cells). In general, neuronal damage was more widespread following administration of kainic acid than domoic acid. In the CA3 region, however, the percentage of cells exhibiting damage was greater following domoic acid (82.1%) than kainic acid (58.8%) following systemic administration. No damage was found in the hippocampi of vehicle control-treated mice. Electron microscopy of the CA3 region following domoic acid revealed two subpopulations of damaged neurons: (1) swollen cells that exhibited vacuolization of their cytoplasm and (2) shrunken irregularly shaped electron-dense cells. Swollen processes of astroglial origin were observed surrounding electron-dense cells, and electron-dense processes were often found extending into the neuropil. These results suggest that although domoic acid and kainic acid produce similar changes in both open field behaviour and hippocampal neuropathology, responses to these toxins are not identical at equitoxic doses. Lesions in the domoic acid-treated mice are more selective for the CA3 hippocampal region than are those produced by kainic acid following systemic administration. Domoic acid may, therefore, be a better tool for studying certain aspects of excitatory amino acid neurotoxicity.
已使用光学和电子显微镜技术研究了海人酸的一种强效结构类似物——软骨藻酸全身给药对小鼠海马体的影响。腹腔注射软骨藻酸（4毫克/千克）或海人酸（32毫克/千克）会引发一系列行为变化，包括镇静、僵硬、刻板行为（抓挠、点头）、平衡失调以及离散性或全身性惊厥。定性和定量组织学分析均显示，在软骨藻酸和海人酸处理的小鼠海马结构中，神经元损伤模式相似但不完全相同。使用这两种毒素时，海马体CA3区域的损伤总是最为广泛，其他海马区域（CA4＞CA1＞CA2＞齿状颗粒细胞）的损伤程度较轻。一般而言，海人酸给药后神经元损伤比软骨藻酸更广泛。然而，在CA3区域，全身给药后显示损伤的细胞百分比，软骨藻酸组（82.1%）高于海人酸组（58.8%）。在溶剂对照处理的小鼠海马体中未发现损伤。软骨藻酸处理后CA3区域的电子显微镜观察显示有两类受损神经元亚群：（1）细胞肿胀，细胞质出现空泡化；（2）细胞皱缩，形状不规则，电子密度高。观察到源自星形胶质细胞的肿胀突起围绕着电子密度高的细胞，且常常发现电子密度高的突起延伸至神经毡。这些结果表明，尽管软骨藻酸和海人酸在旷场行为和海马神经病理学方面产生相似变化，但在等毒性剂量下对这些毒素的反应并不相同。软骨藻酸处理的小鼠海马损伤对CA3区域的选择性高于全身给药后海人酸造成的损伤。因此，软骨藻酸可能是研究兴奋性氨基酸神经毒性某些方面的更好工具。
