Methamphetamine sensitization attenuates the febrile and neuroinflammatory response to a subsequent peripheral immune stimulus.
Methamphetamine sensitization attenuates the febrile and neuroinflammatory response to a subsequent peripheral immune stimulus.
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DOI：
10.1016/j.bbi.2009.12.008
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Johnson RW
中科院分区：
文献类型：
--
作者：
Buchanan JB;Sparkman NL;Johnson RW
甲基苯丙胺 (MA) 的使用与小胶质细胞的激活有关，高剂量时可引起神经毒性。考虑到与 MA 相关的神经炎症环境的变化，我们研究了 MA 致敏（一种刺激性精神病模型和药物成瘾指标）是否会干扰对后续外周免疫刺激的体温调节和神经炎症反应。 C57BL6/J 小鼠腹腔注射 1mg/kg MA 或生理盐水。每天一次，持续 5 天，以产生行为敏感性。最后一次MA注射后72小时，将100μg/kg LPS或盐水与1mg/kg MA或盐水共同施用，并收集血液和脑。在此我们报告，虽然同时给予 LPS 和 MA 并不影响 LPS 诱导的中枢细胞因子 mRNA 的增加，但对 MA 敏感的小鼠表现出对 LPS 的中枢反应减弱。有趣的是，外周对 LPS 的反应不受 MA 致敏的影响。 LPS 后，所有组中血浆细胞因子的增加相似。此外，孤束核中的 c-Fos 表达在各组之间没有差异，这表明 MA 致敏小鼠的外周到大脑的免疫信号是完整的，并且缺陷在于中央细胞因子区室。我们还发现，与非致敏小鼠相比，MA 致敏降低了 LPS 或急性 MA 诱导的小胶质细胞 Iba1 表达。总而言之，这些数据表明 MA 致敏会干扰正常的中枢免疫反应，阻止中枢神经系统有效地响应来自外周免疫系统的信号。
Methamphetamine (MA) use is associated with activation of microglia and, at high doses, can induce neurotoxicity. Given the changes in the neuroinflammatory environment associated with MA, we investigated whether MA sensitization, a model of stimulant psychosis and an indicator of drug addiction, would interfere with the thermoregulatory and neuroinflammatory response to a subsequent peripheral immune stimulus. C57BL6/J mice were given either 1mg/kg MA or saline i.p. once a day for 5 days to produce behavioral sensitization. Seventy-two hours following the last MA injection, 100μg/kg LPS or saline was co-administered with 1mg/kg MA or saline and blood and brains were collected. Here we report that while co-administration of LPS and MA did not affect the LPS-induced increase in central cytokine mRNA, mice sensitized to MA showed an attenuated central response to LPS. Interestingly, the peripheral response to LPS was not affected by MA sensitization. Plasma cytokines increased similarly in all groups after LPS. Further, c-Fos expression in the nucleus of the solitary tract did not differ between groups, suggesting that the periphery-to-brain immune signal is intact in MA-sensitized mice and that the deficit lies in the central cytokine compartment. We also show that MA sensitization decreased LPS- or acute MA-induced microglial Iba1 expression compared to non-sensitized mice. Taken together, these data show that MA sensitization interferes with the normal central immune response, preventing the CNS from efficiently responding to signals from the peripheral immune system.
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影响因子：
5
作者：
Danaceau, Jonathan P.;Deering, Cassandra E.;Wilkins, Diana G.
通讯作者：
Wilkins, Diana G.
影响因子：
8.3
作者：
Ito, D;Tanaka, K;Fukuuchi, Y
通讯作者：
Fukuuchi, Y
DOI：
10.1016/s0169-328x(98)00040-0
发表时间：
1998-06-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
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通讯作者：
Kohsaka, S
影响因子：
2.6
作者：
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通讯作者：
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影响因子：
2.7
作者：
Gaykema, RPA;Goehler, LE;Watkins, LR
通讯作者：
Watkins, LR