The hypothalamo-pituitary axis responses to lipopolysaccharide-induced endotoxemia in mice lacking inducible nitric oxide synthase
The hypothalamo-pituitary axis responses to lipopolysaccharide-induced endotoxemia in mice lacking inducible nitric oxide synthase
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DOI：
10.1016/j.brainres.2006.02.112
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发表时间：
2006-05-17
期刊：
影响因子：
2.9
通讯作者：
Matsumoto, Tetsuro
中科院分区：
文献类型：
--
作者：
Akasaka, Soichiro;Nomura, Masayoshi;Matsumoto, Tetsuro
诱导型NO合成酶（iNOS）产生的一氧化氮（NO）可能与中枢神经系统对免疫刺激的生物学反应有关。为了阐明iNOS在下丘脑-垂体轴对内毒素血症反应中的作用，我们使用iNOS敲除（KO）小鼠，检测了在脂多糖（LPS）诱导的内毒素血症期间，室旁核（PVN）和中央杏仁核（CeAMY）中神经激活标志物c-fos和促肾上腺皮质激素释放激素（CRH）基因转录水平。此外，血清促肾上腺皮质激素（ACTH）水平也检查在内毒素血症。腹腔注射LPS （1 mg/kg）后，无论基因型如何，PVN和CeAMY中c-fas基因表达水平均显著升高。然而，与对照组小鼠相比，iNOS基因的破坏导致PVN中c-fos基因的诱导显著减少。LPS处理导致PVN和CeAMY中CRH mRNA水平显著升高，与基因型无关。然而，与对照组小鼠相比，lps诱导的CRH mRNA上调在iNOS - KO小鼠PVN中明显减弱。相比之下，在CeAMY中没有观察到神经活性或CRH基因转录的基因型差异。与对照组小鼠相比，iNOS KO小鼠血清ACTH对LPS的反应也明显减弱。这些结果表明，inos衍生的NO可能因此在内毒素血症期间对下丘脑-垂体轴的活性起刺激作用。(c) 2006 Elsevier B.V.版权所有
Nitric oxide (NO) generated by inducible NO synthase (iNOS) may be implicated in the biological responses of the central nervous system to immune stimuli. To elucidate the role of iNOS in the hypothalamo-pituitary axis in responses to endotoxemia, using iNOS knockout (KO) mice, we examined the levels of c-fos, a neural activational marker, and corticotropin-releasing hormone (CRH) gene transcription in the paraventricular nucleus (PVN) and central amygdala (CeAMY) during lipopolysaccharide (LPS)-induced endotoxemia. In addition, the serum adrenocorticotropic hormone (ACTH) levels were also examined during endotoxemia. Following the intraperitoneal administration of LPS (1 mg/kg), the levels of the c-fas gene expression significantly increased in the PVN and the CeAMY regardless of the genotype. However, the disruption of the iNOS gene resulted in a significant decrease in the c-fos gene induction in the PVN in comparison to that observed in control mice. LPS administration caused a significant increase in CRH mRNA levels in the PVN and CeAMY regardless of genotype. However, the LPS-induced upregulation of CRH mRNA was significantly attenuated in the PVN of iNOS KO mice in comparison to that in the control mice. In contrast, no such genotype differences in the neural activity or CRH gene transcription were observed in the CeAMY. The serum ACTH responses to LPS were also significantly blunted in the iNOS KO mice in comparison to the control mice. These results suggest that iNOS-derived NO may therefore play a stimulatory role in the activity of the hypothalamo-pituitary axis during endotoxemia. (c) 2006 Elsevier B.V. All rights reserved.