Fosse V M, Fonnum F
Brain Res. 1986 Sep 24;383(1-2):28-37. doi: 10.1016/0006-8993(86)90004-1.
In this study we have performed surgical, chemical and combined surgical/chemical lesions in order to elucidate neurotransmitter mechanisms in the superior colliculus (SC) of albino rats. Visual cortex (VC) ablation reduced high affinity (HA) uptake of D-Asp by 32% in the deafferented SC. Local injection of kainic acid (KA) into SC reduced HA D-Asp uptake selectively in the lower dose range (less than 1 nmol) by 50-60%. The GABAergic marker glutamate decarboxylase (GAD) was decreased by maximally 60% only at doses exceeding 2 nmol. Choline acetyltransferase (ChAT), however, was not affected at any of the doses administered. VC ablation provided an almost complete protection against 1 nmol KA. When KA was injected 2 days prior to VC ablation an additive effect on HA D-Asp uptake of the two lesions was observed. From these observations we infer that the notion of a glutamatergic projection from VC to SC has been strengthened. Moreover, local neurons in intermediate layers account for about 60% of the HA D-Asp uptake in SC, and these are most likely impinged upon by the glutamatergic afferents. The neurotoxic effects of KA were compared with those of some suspected endogenous excitotoxins, i.e. N-methyl tetrahydrofolic acid (Me-THF), other folates and the tryptophan metabolite quinolinic acid (QA). N-methyl tetrahydrofolic acid, Me-THF (4 and 10 nmol) reduced HA D-Asp uptake by about 50%, only when coinjected with ascorbic acid. GAD and ChAT were not affected at either of the doses. QA was about 100-fold less potent than KA on a molar basis, and the maximal reduction of GAD was similar in QA and KA injected animals, whereas the maximal reduction of HA D-Asp was only 40% after QA injection in SC. We conclude that Me-THF, QA and KA exert their neurotoxic actions by different mechanisms as judged by the behavioral, histopathological and biochemical sequelae seen after local injections of the respective substances in intermediate layers of SC and corroborate data obtained from other brain areas.
在本研究中，我们进行了手术、化学及手术/化学联合损伤，以阐明白化大鼠上丘（SC）中的神经递质机制。视觉皮层（VC）切除使去传入神经的SC中D-天冬氨酸的高亲和力（HA）摄取减少32%。向下丘局部注射海藻酸（KA）在低剂量范围（小于1 nmol）时选择性地使HA D-天冬氨酸摄取减少50 - 60%。仅在剂量超过2 nmol时，GABA能标记物谷氨酸脱羧酶（GAD）最大减少60%。然而，胆碱乙酰转移酶（ChAT）在任何给药剂量下均未受影响。VC切除对1 nmol KA提供了几乎完全的保护作用。当在VC切除前2天注射KA时，观察到两种损伤对HA D-天冬氨酸摄取有相加作用。从这些观察结果我们推断，从VC到SC存在谷氨酸能投射这一观点得到了加强。此外，中间层的局部神经元约占SC中HA D-天冬氨酸摄取的60%，并且这些神经元很可能受到谷氨酸能传入纤维的影响。将KA的神经毒性作用与一些可疑的内源性兴奋性毒素，即N-甲基四氢叶酸（Me-THF）、其他叶酸以及色氨酸代谢产物喹啉酸（QA）的神经毒性作用进行了比较。仅在与抗坏血酸共同注射时，N-甲基四氢叶酸，Me-THF（4和10 nmol）使HA D-天冬氨酸摄取减少约50%。两种剂量下GAD和ChAT均未受影响。按摩尔计算，QA的效力比KA弱约100倍，并且在注射QA和KA的动物中，GAD的最大减少相似，而在SC中注射QA后，HA D-天冬氨酸的最大减少仅为40%。我们得出结论，根据在SC中间层局部注射各自物质后观察到的行为、组织病理学和生化后遗症判断，Me-THF、QA和KA通过不同机制发挥其神经毒性作用，并证实了从其他脑区获得的数据。
