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印防己毒素对小鼠作用所诱导的神经内分泌、行为及巨噬细胞活性变化

Neuroendocrine, behavioral and macrophage activity changes induced by picrotoxin effects in mice.

作者信息

Stankevicius D, Rodrigues-Costa E C, Camilo Flório J, Palermo-Neto J

机构信息

Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, São Paulo, SP, Brazil.

出版信息

Neuropharmacology. 2008 Feb;54(2):300-8. doi: 10.1016/j.neuropharm.2007.09.011. Epub 2007 Oct 7.

Abstract

The relevance and property of studies related to stress effects on immune function are undisputable. All studies conducted on stress-immune relationships, however, provide from physical and/or psychological stressors. Indeed, as far as it is of our knowledge brain-innate immune responses were not analyzed after anxiogenic-like drugs use. The present experiment was then undertaken to analyze the effects of picrotoxin (0.3, 0.6 and 1.0mg/kg doses) on behavior, macrophage activity, serum corticosterone and noradrenaline (NE) levels and turnover in the brain of adult mice. Results showed that picrotoxin treatment in mice: (1) decreased motor and rearing activities in an open-field; (2) decreased the number of entries into the plus-maze open-arms and decreased the time spent in the exploration of the plus-maze open-arms; (3) decreased both motor activity and the level of holes exploration in the hole-board; (4) increased the levels of serum corticosterone in dose-dependent way; (5) increased noradrenaline (NE) and MHPG levels and NE turnover in the hypothalamus; and (6) increased Staphylococcus aureus and PMA-induced macrophage oxidative burst. However, and contrary to that reported after physical or psychological stress, this drug induced no effects on macrophage phagocytosis and NE levels and turnover in the frontal cortex. The present results are thus showing that picrotoxin induces some but not all neuro-innate immunity changes previously reported for inescapable foot-shock and psychological stressors in mice. These facts suggest that this chemical stressor triggers CNS pathways that might be somehow different from those fired by inescapable foot-shock and psychological stressors, leading to different neuro-innate immune responses.

摘要

与应激对免疫功能影响相关的研究的相关性和性质是无可争议的。然而,所有关于应激与免疫关系的研究均来自身体和/或心理应激源。事实上,就我们所知,在使用致焦虑样药物后,尚未分析脑内先天免疫反应。因此,本实验旨在分析印防己毒素(0.3、0.6和1.0mg/kg剂量)对成年小鼠行为、巨噬细胞活性、血清皮质酮和去甲肾上腺素(NE)水平以及脑内周转率的影响。结果表明,印防己毒素对小鼠的处理:(1)在旷场中降低运动和直立活动;(2)减少进入十字迷宫开放臂的次数,并减少在十字迷宫开放臂探索中花费的时间;(3)降低洞板中的运动活性和洞探索水平;(4)以剂量依赖方式增加血清皮质酮水平;(5)增加下丘脑去甲肾上腺素(NE)和3-甲氧基-4-羟基苯乙二醇(MHPG)水平以及NE周转率;(6)增加金黄色葡萄球菌和佛波酯诱导的巨噬细胞氧化爆发。然而,与身体或心理应激后报道的情况相反,该药物对额叶皮质中的巨噬细胞吞噬作用以及NE水平和周转率没有影响。因此,目前的结果表明,印防己毒素诱导了一些但并非所有先前报道的小鼠不可逃避的足部电击和心理应激源所引起的神经先天免疫变化。这些事实表明,这种化学应激源触发的中枢神经系统途径可能在某种程度上不同于不可逃避的足部电击和心理应激源所激发的途径,从而导致不同的神经先天免疫反应。

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