Shin K
Rinsho Shinkeigaku. 1991 Dec;31(12):1313-5.
A single systemic injection of acromelic acid, a novel kainate analogue, caused long-lasting spastic paraparesis in the rat. Two rats that developed paraparesis were neuropathologically examined one week and three months after the injection, respectively. Numerous degenerated neurons with marked reactive gliosis were scattered in the gray matter of the spinal cord of the rat with paraparesis for one week. Degenerated neurons were most abundant in the core part of lumbar and sacral segments. The cytometry on the 1st sacral segment disclosed that the number of small neurons was significantly decreased. No morphological sign of neuron damage was demonstrated in the rest of the central nervous system. These pathological changes were responsible for the development of characteristic behavioral changes which were quite different from those induced by kainic acid. The regional difference between the neuron damage induced by acromelic acid and that induced by kainic acid suggests the presence of plural kinds of kainate receptor subtypes in the rat central nervous system. This assumption is supported by receptor binding studies on glutamate receptor subtypes, indicating the low affinity of acromelic acid for both kainate and AMPA binding sites. Acromelic acid may exert its potent depolarizing and neurotoxic effects through activating a new class of kainate receptor subtypes.
单次全身注射一种新型的红藻氨酸类似物——肢端黑素酸，可导致大鼠出现持久的痉挛性截瘫。分别在注射后1周和3个月对2只出现截瘫的大鼠进行神经病理学检查。在出现截瘫1周的大鼠脊髓灰质中，散在分布着许多变性神经元以及明显的反应性胶质细胞增生。变性神经元在腰段和骶段的核心部位最为丰富。对第1骶段进行细胞计数发现，小神经元数量显著减少。中枢神经系统的其他部位未发现神经元损伤的形态学迹象。这些病理变化导致了特征性行为改变的出现，这些改变与红藻氨酸诱导的改变截然不同。肢端黑素酸诱导的神经元损伤与红藻氨酸诱导的损伤之间的区域差异表明，大鼠中枢神经系统中存在多种红藻氨酸受体亚型。这一假设得到了谷氨酸受体亚型受体结合研究的支持，该研究表明肢端黑素酸对红藻氨酸和AMPA结合位点的亲和力较低。肢端黑素酸可能通过激活一类新的红藻氨酸受体亚型来发挥其强大的去极化和神经毒性作用。
