一个中枢炎性免疫诱发长时程抑郁样行为的新模型
A New Animal Model of Depression Induced by Repeated Central Lipopolysaccharide Administration
查看参考文献37篇
|
文摘
|
脂多糖(lipopolysaccharide, LPS)免疫激活模型是研究抑郁症细胞因子假说的重要动物模型, 目前国际上常用外周单次LPS 注射诱发抑郁样行为, 但该模型中抑郁样行为持续仅有数小时。为建立诱发较长时程抑郁样行为的免疫激活动物模型, 本研究尝试侧脑室注射LPS 激活大鼠中枢免疫炎性反应, 考察单次以及重复中枢LPS 注射诱发抑郁样行为的效果, 以及中枢炎性免疫诱发行为改变的时程。结果显示:单次中枢LPS 注射后24 h 只能诱发旷场自发活动和探索行为下降等部分抑郁样行为, 未能诱导糖水偏好下降和悬尾不动时间增加; 3次重复注射则在末次LPS 注射后24 h 表现出显著的糖水偏好下降, 自发活动和探索行为减少, 悬尾不动时间增加等行为。且自发活动、探索行为减少和悬尾不动时间增加能够延续至末次LPS注射后72 h。这些结果表明脑室重复LPS 注射可诱发较长时程的抑郁样行为, 这种新的中枢炎性免疫激活诱发的抑郁症模型, 为研究抑郁症炎性免疫机制提供了更为有效的动物模型, 有助于深入探讨行为和免疫功能间的复杂关系。 |
|
其他语种文摘
|
The administration of lipopolysaccharide (LPS), a component of the cell wall of gram negative bacteria, is commonly-used method to cause immune activation and the release of cytokines both in the periphery and in the brain in rodents. The cytokine theory of depression indicated that pro-inflammatory cytokines play an important role in the pathological mechanism of depression. Many studies used the peripheral administration of LPS to induce depressive-like behaviors. However, in these studies, the altered behaviors usually last only a few hours, seldom longer than 24h. Such short-term depressive behavior can hardly be regarded as a model of depression.. Thus, the aim of the present study was therefore to develop a new animal model of depression with apparent depressive-like behavior at - and after- 24h post-LPS injection. In this study, single and triple central LPS administration were used to induce depressive-like behavior respectively. Sprague-Dawley rats were randomly divided into LPS group and control group. LPS (100ng/rat, one injection; or once every second day, total three times) or isotonic saline was administered by intracerebroventricular microinjection. The depressive-like behavior was measured by preference to saccharin, locomotor activity and immobility time of tail suspension. The result indicated that single central LPS injection induced partial depressive-like behaviors. There was significant difference in locomotor activity, but not in the preference of saccharin and immobility time of tail suspension. However, repeated central LPS administration induced significant depressive-like behaviors after 24h of the last LPS injection. The animals with triple central LPS administration consumed less saccharin solution, exhibited less locomotor activity in the open field, and maintained immobility time in tail suspension. The changes in locomotor activity and immobility time of tail suspension were even apparent until 72h after the last LPS injection. Our results demonstrate that a new effective model of depression can be established by means of repeated lateral ventricle LPS injections, and the induced depressive-like behavior has longer time duration than by the peripheral injection of LPS. |
|
来源
|
心理学报
,2014,46(5):639-646 【核心库】
|
|
关键词
|
抑郁样行为
;
脂多糖
;
中枢炎性免疫
;
时程效应
|
|
地址
|
中国科学院心理研究所, 中国科学院心理健康重点实验室, 北京, 100101
|
|
语种
|
中文 |
|
文献类型
|
研究性论文 |
|
ISSN
|
0439-755X |
|
学科
|
社会科学总论 |
|
基金
|
中国科学院知识创新工程项目
;
国家自然科学基金项目
|
|
文献收藏号
|
CSCD:5137912
|
参考文献 共
37
共2页
|
|
1.
Bluthe R M. Central injection of IL-10 antagonizes the behavioural effects of lipopolysaccharide in rats.
Psychoneuroendocrinology,1999,24:301-311
|
被引
4
次
|
|
|
|
|
2.
池少鹏. 脂多糖激活所致大鼠抑郁样行为及对海马神经细胞钾电流变化的影响.
心理学报,2012,44:459-468
|
被引
1
次
|
|
|
|
|
3.
Dantzer R. Cytokine-induced sickness behaviour: A neuroimmune response to activation of innate immunity.
European Journal of Pharmacology,2004,500:399-411
|
被引
10
次
|
|
|
|
|
4.
Dantzer R. Cytokine, sickness behavior, and depression.
Immunology and Allergy Clinics of North America,2009,29:247-264
|
被引
12
次
|
|
|
|
|
5.
Dantzer R. From inflammation to sickness and depression: when the immune system subjugates the brain.
Nature Reviews Neuroscience,2008,9:46-56
|
被引
97
次
|
|
|
|
|
6.
De La Garza R I. Chronic lypopolysaccharide results in tolerance to alterations to basic reward behavior, body weight, and food and water consumption.
Biol Psychiatry,2004,55:112S
|
被引
1
次
|
|
|
|
|
7.
Draisma A. Development of endotoxin tolerance in humans in vivo.
Critical Care Medicine,2009,37:1261-1267
|
被引
5
次
|
|
|
|
|
8.
Frenois F. Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior.
Psychoneuroendocrinology,2007,32:516-531
|
被引
6
次
|
|
|
|
|
9.
Fu X. Central administration of lipopolysaccharide induces depressive-like behavior in vivo and activates brain indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures.
Journal of Neuroinflammation,2010,7:43
|
被引
6
次
|
|
|
|
|
10.
Himmerich H. Depression, comorbidities and the TNF-α system.
European Psychiatry,2008,23:421-429
|
被引
6
次
|
|
|
|
|
11.
Howren M B. Associations of depression with c-reactive protein, IL-1, and IL-6: A meta-analysis.
Psychosomatic Medicine,2009,71:171-186
|
被引
57
次
|
|
|
|
|
12.
Inoue W. Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharideinduced fever.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology,2008,295:R133-R143
|
被引
1
次
|
|
|
|
|
13.
Kettenmann H. Physiology of microglia.
Physiological Reviews,2011,91(2):461-553
|
被引
79
次
|
|
|
|
|
14.
Kubera M. A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months.
Brain, Behavior, and Immunity,2013,31:96-104
|
被引
7
次
|
|
|
|
|
15.
Lehner M D. Endotoxin tolerance - Mechanisms and beneficial effects in bacterial infection.
Reviews of Physiology, Biochemistry and Pharmacology,2002,144:95-141
|
被引
5
次
|
|
|
|
|
16.
Leonard B. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression.
Neuroscience & Biobehavioral Reviews,2012,36:764-785
|
被引
15
次
|
|
|
|
|
17.
Maes M. "Functional" or "psychosomatic" symptoms, e.g. a flu-like malaise, aches and pain and fatigue, are major features of major and in particular of melancholic depression.
Neuro Endocrinology Letters,2009,30:564-573
|
被引
2
次
|
|
|
|
|
18.
Maes M. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways.
BMC Medicine,2012,10:66
|
被引
14
次
|
|
|
|
|
19.
Maes M. Increased IgA and IgM responses against gut commensals in chronic depression: Further evidence for increased bacterial translocation or leaky gut.
Journal of Affective Disorders,2012,141:55-62
|
被引
9
次
|
|
|
|
|
20.
Maes M. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression.
Metabolic Brain Disease,2009,24:27-53
|
被引
18
次
|
|
|
|
|
了解气象卫星更多信息，请访问