Discriminable excitotoxic effects of ibotenic acid, AMPA, NMDA and quinolinic acid in the rat laterodorsal tegmental nucleus
Discriminable excitotoxic effects of ibotenic acid, AMPA, NMDA and quinolinic acid in the rat laterodorsal tegmental nucleus
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DOI：
10.1016/s0006-8993(97)00101-7
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发表时间：
1997-04-25
期刊：
影响因子：
2.9
通讯作者：
Semba, K
中科院分区：
文献类型：
--
作者：
Inglis, WL;Semba, K
兴奋毒素是神经科学研究中的宝贵工具，因为它们可以帮助我们发现某些神经元对不同类型行为的必要程度。它们具有独特的神经毒性作用，这取决于它们被注入的位置，本研究的目的是描述兴奋性毒素在背外侧被盖核（LDTg）的神经毒性特征。在戊巴比妥或Avertin麻醉下，将0.1 M鹅膏蕈氨酸盐、0.1 M喹啉酸盐、0.04-0.1 M NMDA或0.05-0.015 M AMPA的两次0.1 μ l输注单侧注入LDTg。注射针在中外侧平面中与垂直方向成24度角。23-27天后，使用标准组织学程序处理通过中桥脑被盖的切片，用于NADPH-黄递酶组织化学、酪氨酸羟化酶或5-羟色胺免疫组织化学和甲酚紫。根据受损区域的大小（通过反应性胶质增生确定）、中桥脑被盖胆碱能细胞损失的程度（通过计数NADPH-黄递酶阳性神经元）以及蓝斑和中缝背核诱导的神经元损失来评估病变。鹅膏蕈氨酸在LDTg中引起致密病变（超过80%的胆碱能损失），对蓝斑和中缝背核的损伤很小。喹啉酸盐和低剂量的AMPA和NMDA的胆碱能损失小于35%的非常小的病变，而在较高的剂量，AMPA和NMDA诱导大面积的反应性胶质增生，但只杀死一部分的胆碱能神经元。AMPA似乎对蓝斑中的去甲肾上腺素能神经元具有特别的亲和力，注射到LDTg中的0.015 M剂量通常会破坏大多数这些神经元。结果进行了讨论的背景下，什么是已知的兴奋性毒素和谷氨酸受体的中桥脑神经元的机制。
Excitotoxins are valuable tools in neuroscience research as they can help us to discover the extent to which certain neurones are necessary for different types of behaviour. They have distinctive neurotoxic effects depending on where they are infused, and this study was conducted to delineate the neurotoxic profiles of excitotoxins in the laterodorsal tegmental nucleus (LDTg). Two 0.1 mu l infusions of 0.1 M ibotenate, 0.1 M quinolinate, 0.04-0.1 M NMDA, or 0.05-0.015 M AMPA, were made unilaterally into the LDTg under either pentobarbitone or Avertin anaesthesia. The injection needle was oriented at an angle of 24 degrees from vertical in the mediolateral plane. After 23-27 days, sections through the mesopontine tegmentum were processed using standard histological procedures for NADPH-diaphorase histochemistry, tyrosine hydroxylase or 5-hydroxytryptamine immunohistochemistry, and Cresyl violet. Lesions were assessed in terms of the size of the damaged area (identified by reactive gliosis), the extent of cholinergic cell loss in the mesopontine tegmentum (by counting NADPH-diaphorase-positive neurones), and neuronal loss induced in the locus coeruleus and dorsal raphe nucleus. Ibotenate induced compact lesions in the LDTg (more than 80% cholinergic loss) and did little damage to the locus coeruleus and dorsal raphe nucleus. Quinolinate and low doses of AMPA and NMDA made very small lesions with less than 35% cholinergic loss, while at higher doses, AMPA and NMDA induced large areas of reactive gliosis but killed only a proportion of the cholinergic neurones. AMPA appeared to have a particular affinity for noradrenergic neurones in the locus coeruleus, with the 0.015 M dose injected into the LDTg typically destroying the majority of these neurones. The results are discussed in the context of what is known about the mechanisms of excitotoxins and the glutamate receptor profile of mesopontine neurones.