Hippocampal lesions indicate differences between the excitotoxic properties of acidic amino acids
Hippocampal lesions indicate differences between the excitotoxic properties of acidic amino acids
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海马损伤表明酸性氨基酸的兴奋毒性特性之间存在差异
DOI：
10.1016/0006-8993(79)91018-7
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发表时间：
1979
期刊：
影响因子：
2.9
通讯作者：
K. Fuxe
中科院分区：
文献类型：
--
作者：
C. Köhler;R. Schwarcz;K. Fuxe
kainic acid（一种构象受限的谷氨酸类似物）损伤纹状体神经元，为亨廷顿病（HD）提供了一种动物模型2,5。经形态学和生化评估，将kainic acid立体定向显微注射到其他脑区也会导致选择性神经元变性5,1a, 14,15。在海马形成过程中，KA引起的颗粒细胞变性依赖于谷氨酸传导通路纤维的完整性7。这一点，以及去皮后纹状体神经元的类似保护，表明谷氨酸在KA 1,9的神经毒性作用中起主要作用。ibotenic acid （Ibo）是一种从蘑菇Amanita muscaria中分离出来的异恶唑，在肠腔内注射ibotenic acid （Ibo）会导致与KA输注后非常相似的病变模式。在本研究中，我们调查，在大鼠海马形成，这些酸性氨基酸之间的分歧的可能性，关于它们的神经毒性特性。所有实验均以Wistar品系雄性Sprague-Dawley白化大鼠（Anticimex，瑞典，250-300 g体重）为实验对象。在注射氨基酸前3至5天，根据先前描述的方法横切穿孔路径和海马连接纤维7。所有动物的联合系统与穿孔通路一起被切断，因为有报道称同侧退变后对侧穿孔通路可能在齿状体中萌发19。
Lesions of striatal neurons with kainic acid (KA), a conformationally restricted analogue of glutamic acid, provide an animal model for Huntington's disease (HD) 2, s. Stereotaxic microinjection of KA into other brain regions too, causes selective neuronal degeneration as assessed morphologically and biochemically 5, 1a, 14, 1s. In the hippocampal formation, degeneration of granule cells by KA has been shown to depend on the integrity of glutamatergic perforant path fibres 7. This, as well as analogous protection of striatal neurons after decortication, suggests a major role of glutamate in the neurotoxic action of KA 1, 9. Intrastriatal injections of ibotenic acid (Ibo), an isoxazole isolated from the mushroom Amanita muscaria, result in a lesion pattern which closely resembles that after KA infusions15, in. In the present study we investigate, in the hippocampal formation of the rat, the possibility of divergences between those acidic amino acids, concerning their neurotoxic properties.All experiments were carried out on male Sprague-Dawley albino rats of the Wistar strain (Anticimex, Sweden, 250-300 g body weight). Three to five days before injection of the amino acids the perforant path and the hippocampal commissural fibres were transected according to a previously described method 7. All animals had the commissural system cut together with the perforant path, since it has been reported that the contralateral perforant path may sprout in the dentate after ipsilateral degeneration 19.