Pro-inflammatory immune-to-brain signaling is involved in neuroendocrine responses to acute emotional stress
Pro-inflammatory immune-to-brain signaling is involved in neuroendocrine responses to acute emotional stress
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促炎性免疫脑信号传导参与对急性情绪压力的神经内分泌反应
DOI：
10.1016/j.bbi.2017.02.003
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Sawchenko PE
中科院分区：
文献类型：
--
作者：
Serrats J;Grigoleit JS;Alvarez-Salas E;Sawchenko PE
炎症应激源（如细菌脂多糖）激活下丘脑-垂体-肾上腺（HPA）轴被认为涉及循环细胞因子的血管转导，血管周围巨噬细胞（pvm）和内皮细胞，通过诱导（环氧化酶-2或cox -2依赖性）前列腺素合成影响HPA控制回路的激活。为了测试这种机制的应激源特异性，我们研究了pvm消融或COX活性的药物阻断是否会影响HPA对一种代表性情绪应激源——约束的反应。将大鼠暴露在单一30分钟的急性抑制发作中，应激后0-2小时，至少有一种促炎细胞因子、IL-6、小胶质细胞活化和多种脑血管活化指标（包括COX-2表达和脑前列腺素e2水平升高）的血浆水平升高。非选择性COX抑制剂吲哚美辛预处理，icv （10 μg / 5 μl）或iv （1 mg/kg）均可显著降低室旁下丘脑核（PVH）中抑制诱导的Fos表达，较对照降低45%。在脑pvm消融后5-7天暴露于急性抑制的大鼠中，通过静脉注射包封双膦酸盐药物氯膦酸盐的脂质体，可以观察到PVH激活反应降低75%。注射氯膦酸脂质体的大鼠体内ACTH和皮质酮的基础血浆水平没有改变，但与预先注射含盐脂质体的动物相比，抑制诱导的HPA分泌反应的峰值幅度大大降低。这些发现支持了pvm诱导前列腺素合成在HPA对急性抑制（一种典型的情绪应激源）的反应中意想不到的突出作用。
Activation of the hypothalamo-pituitary-adrenal (HPA) axis by inflammatory stressors (e.g., bacterial lipopolysaccharide) is thought to involve vascular transduction of circulating cytokines, with perivascular macrophages (PVMs) along with endothelia, effecting activation of HPA control circuitry via inducible (cyclooxygenase-2- or COX-2-dependent) prostaglandin synthesis. To test the stressor-specificity of this mechanism, we examined whether ablation of PVMs or pharmacologic blockade of COX activity affected HPA responses to a representative emotional stressor, restraint. Exposing rats to a single 30 min acute restraint episode provoked increased plasma levels of at least one proinflammatory cytokine, IL-6, microglial activation and multiple indices of cerebrovascular activation, including COX-2 expression and increased brain prostaglandin E2levels at 0–2 h after stress. Pretreatment with the nonselective COX inhibitor, indomethacin, either icv (10 μg in 5 μl) or iv (1 mg/kg) significantly reduced restraint-induced Fos expression in the paraventricular hypothalamic nucleus (PVH) by 45%, relative to vehicle-injected controls. A 75% reduction of the PVH activational response was seen in rats exposed to acute restraint 5–7 days after ablation of brain PVMs by icv injection of liposomes encapsulating the bisphosphonate drug, clodronate. Basal plasma levels of ACTH and corticosterone were not altered in clodronate liposome-injected rats, but the peak magnitude of restraint-induced HPA secretory responses was substantially reduced, relative to animals pretreated with saline-filled liposomes. These findings support an unexpectedly prominent role for inducible prostaglandin synthesis by PVMs in HPA responses to acute restraint, a prototypic emotional stressor.
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截然不同的急性应激源在下丘脑室旁核中引起不同的转录谱。
DOI：
10.1523/jneurosci.23-13-05607.2003
发表时间：
2003
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Reyes,TeresaM;Walker,JohnR;DeCino,Casey;Hogenesch,JohnB;Sawchenko,PaulE
通讯作者：
Sawchenko,PaulE
固定应激可能通过中枢和外周儿茶酚胺增加血浆白介素 6。
影响因子：
2.4
作者：
A. Takaki;Qin;A. Somogyvári;A. Arimura
通讯作者：
A. Arimura
影响因子：
2.9
作者：
Helfferich, F;Palkovits, M
通讯作者：
Palkovits, M
影响因子：
7.6
作者：
Madrigal, JLM;Moro, MA;Leza, JC
通讯作者：
Leza, JC
炎症：抑郁症迷在高温下火焰和盛宴。
DOI：
10.1176/appi.ajp.2015.15020152
发表时间：
2015-11-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Kiecolt-Glaser JK;Derry HM;Fagundes CP
通讯作者：
Fagundes CP