Histamine infusion induces a selective dopaminergic neuronal death along with an inflammatory reaction in rat substantia nigra
Histamine infusion induces a selective dopaminergic neuronal death along with an inflammatory reaction in rat substantia nigra
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DOI：
10.1046/j.1471-4159.2000.0750540.x
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发表时间：
2000-08-01
影响因子：
4.7
通讯作者：
Machado, A
中科院分区：
文献类型：
--
作者：
Vizuete, ML;Merino, M;Machado, A
我们评估了直接输注组胺作为炎症反应介质对黑质、纹状体、内侧隔膜和内侧丘系的影响。在黑质中注射 100 和 250 nmol 组胺对多巴胺能神经元产生选择性损伤，表现为酪氨酸羟化酶 mRNA 表达细胞、酪氨酸羟化酶免疫标记阳性细胞体以及多巴胺和 3,4-二羟基苯乙酸水平的损失。与此同时，我们发现急性炎症反应，表现为神经胶质原纤维酸性蛋白免疫标记星形胶质细胞的丧失，并且在完全相同的区域，小胶质细胞被激活。在纹状体中，只有高剂量（500 nmol）才会产生明显的终末变性。黑质中谷氨酸脱羧酶 mRNA 的转录未改变，证明了组胺对多巴胺能细胞的选择性神经毒性。此外，间隔内注射 100 nmol 组胺未能改变胆碱乙酰转移酶 mRNA 表达细胞的模式。在内侧丘系实质内注射组胺未能改变血清素免疫标记细胞的模式。我们的结论是，黑质对组胺衍生的神经毒性高度敏感，其中组胺介导的炎症过程可能在组胺输注后导致多巴胺能神经元损伤的病理变化中发挥重要作用。
We have evaluated the effects of a direct infusion of histamine, as mediator of inflammatory response, in substantia nigra, striatum, medial septum, and medial lemniscus. Injection of 100 and 250 nmol of histamine in substantia nigra produced a selective damage in dopaminergic neurons evidenced by the loss of tyrosine hydroxylase mRNA-expressing cells, tyrosine hydroxylase-immunolabeled-positive cell bodies, and dopamine and 3,4-dihydroxyphenylacetic acid levels. In parallel we found an acute inflammatory response manifested by a loss of glial fibrillary acidic protein-immunolabeled astrocytes and, at precisely the same area, an activation of microglia. In the striatum, only high doses (500 nmol) produced an evident terminal degeneration. The selective neurotoxicity of histamine for dopaminergic cells was demonstrated by the unaltered transcription of glutamic acid decarboxylase mRNA in substantia nigra. Moreover, intraseptal injection of 100 nmol of histamine failed to alter the pattern of choline acetyltransferase mRNA-expressing cells. and intraparenchymal injection of histamine in medial lemniscus failed to alter the pattern of serotonin-immunolabeled cells. We conclude that the substantia nigra is highly sensitive to histamine-derived neurotoxicity, where inflammatory processes mediated by histamine could be important in the pathological changes that lead to dopaminergic neuronal damage after histamine infusion.