Involvement of brain endogenous histamine in the degeneration of dopaminergic neurons in 6-hydroxydopamine-lesioned rats
Involvement of brain endogenous histamine in the degeneration of dopaminergic neurons in 6-hydroxydopamine-lesioned rats
复制标题
DOI：
10.1016/j.neuropharm.2007.08.014
复制
发表时间：
2007-12-01
影响因子：
4.7
通讯作者：
Luo, Jian-Hong
中科院分区：
文献类型：
--
作者：
Liu, Chun-Qing;Chen, Zhong;Luo, Jian-Hong
先前的研究表明脑组织胺参与帕金森病（PD）的发病机制，但内源性组胺在黑质致密部（SNpc）多巴胺能神经元变性中的作用仍不清楚。我们的目的是通过在 PD 动物模型（即 6-羟基多巴胺 (6-OHDA) 损伤的大鼠）中给予组胺能药物和施用组胺受体拮抗剂来改变脑组胺水平来研究这个问题。在盐水处理的动物中，6-OHDA 输注导致阿扑吗啡诱导的转向率逐渐增加，并导致 SNpc 中酪氨酸羟化酶免疫反应性 (TH-ir) 神经元的损失，在 6-OHDA 输注后 1、7 或 14 天之前每天给予组胺能药物。组氨酸（500 mg/kg，腹腔注射）。它是组胺的前体，增加了转变率（第7天分别为27%和第14天为26%，P < 0.05），并且TH-ir神经元的损失也增加，但仅在第1天和第7天（损失分别为67% vs 47%和90.4% vs 74%，P < 0.05）。相比之下。 α-氟甲基组氨酸（α-FMH，25μg，静脉注射）。组氨酸脱羧酶 (HDC) 的不可逆抑制剂，显着降低了转变率（第 7 天为 25%，第 14 天为 26%，P < 0.05），并且仅在第 1 天和第 7 天防止了 TH-ir 神经元的损失（损失分别为 28% vs 47% 和 58% vs 74%，P < 0.05）。此外。组胺 H1 受体拮抗剂吡拉明（5 μg，静脉注射），而非 H1 受体拮抗剂西咪替丁（5 μg，静脉注射）也降低了转化率（第 7 天分别为 38%，第 14 天为 21%，P < 0.05），并防止了第 1 天和第 7 天的 TH-ir 神经元损失（38% vs 5 1% 和 60% vs 6-OHDA损伤后第14天，所有不同治疗组的TH-ir神经元数量没有显着差异，这些结果表明，内源性组胺可能通过其H1受体加速多巴胺能神经元的退化，而组胺传递的减弱可能在6-OHDA损伤发展的早期对其起到保护作用。 PD 大鼠。(c) 2007 Elsevier Ltd. 保留所有权利。
Previous studies have suggested that brain histamine is involved in the pathogenesis of Parkinson's disease (PD), but the role of endogenous histamine in the degeneration of dopaminergic neurons in the substantia nigra pars compact (SNpc) remains unclear. We aimed to investigate this issue by changing the brain histamine levels by giving histaminergic agents, and administrating histamine receptor antagonists in the PD animal model, i.e. the 6-hydroxydopamine (6-OHDA)-lesioned rat. In saline-treated animals, 6-OHDA infusion produced a progressive increase in apomorphine-induced turning rate and a loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the SNpc, Histaminergic agents were given prior and daily for 1, 7 or 14 days after 6-OHDA infusion. Histidine (500 mg/kg, i.p.). it precursor of histamine, increased the turning rate (27% on day 7 and 26% on day 14, respectively, P < 0.05) and also the loss of TH-ir neurons, but only on day 1 and 7 (67% vs 47% and 90.4% vs 74% loss, respectively, P < 0.05). In contrast. alpha-fluoromethylhistidine (alpha-FMH, 25 mu g, i.c.v.). an irreversible inhibitor of histidine decarboxylase (HDC), significantly decreased the turning rate (25% on day 7 and 26% on day 14, respectively P < 0.05) and prevented the loss of TH-ir neurons, also only on day 1 and day 7 (28% vs 47% and 58% vs 74% loss, respectively P < 0.05). In addition. the histamine H, receptor antagonist pyrilamine (5 mu g, i.c.v.), but not the H, receptor antagonist cimetidine (5 mu g. i.c.v.), also decreased the turning rate (38% on day 7 and 21 % on day 14, respectively, P < 0.05) and prevented the loss of TH-ir neurons on day I and (lay 7 (38% vs 5 1 % and 60% vs 78% loss, respectively, P < 0.05). On day 14 after 6-OHDA lesion, there were no significant differences in the number of TH-ir neurons among all the different treatment groups. Taken together, these findings indicate that enclogenous histamine may accelerate the degeneration of dopaminergic neurons via its H, receptor, while attenuation of histamine transmission may play a protective role on it in the early stage of development of 6-OHDA lesioned PD rats. (c) 2007 Elsevier Ltd. All rights reserved.