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Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats
Wang, Donglin1,3; Lin, Wenjuan1,2; Pan, Yuqin1,3; Kuang, Xueying1; Qi, Xiaoli1; Sun, Han1,3; Lin, WJ (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, 4A Datun Rd, Beijing 100101, Peoples R China.
2011-05-01
发表期刊BRAIN BEHAVIOR AND IMMUNITY
ISSN0889-1591
文章类型Article
卷号25期号:4页码:706-714
产权排序1
摘要

Although accumulating evidence supports a role for cytokines in the pathophysiology of depression, the cytokine hypothesis of depression is debatable. It has been suggested that neuroendocrine and immune systems acting in concert may have roles in the development and the maintenance of the disease. Glucocorticoid receptor (GR) is the key element which exerts both anti-inflammatory and cytokineinhibiting effects. Whether functional changes of GR are involved in the pathophysiology of cytokineinduced depression remains elusive. In the present study, the effects of both acute and chronic GR blockade on depressive-like behaviour and cytokine production induced by lipopolysaccharides (LPS), cytokine inducer, were investigated in rats. Acute or chronic blockade of GR was achieved by a single administration or repeated administrations, respectively, of the GR antagonist RU486 (RU). Behavioural measurements, including saccharin preference, locomotor activity, and immobility time, were assessed. The serum levels of proinflammatory cytokines (TNFa, IL-1b, and IFNc) were determined by ELISA. The results showed that LPS induced significant but transient depressive-like behaviour. Repeated, but not single, administration of RU significantly enhanced and prolonged LPS-induced depressive-like behavior and an increase in the serum production of TNFa and IFNc. These results indicate that the effective blockade of GR enhanced the depressive-like behaviour induced by cytokines. Findings from this study suggest that GR dysfunction may be an important contributing factor to the development of cytokine-related depression. These findings add to the growing evidence of mechanisms by which cytokines influence depression.

; Although accumulating evidence supports a role for cytokines in the pathophysiology of depression, the cytokine hypothesis of depression is debatable. It has been suggested that neuroendocrine and immune systems acting in concert may have roles in the development and the maintenance of the disease. Glucocorticoid receptor (GR) is the key element which exerts both anti-inflammatory and cytokine-inhibiting effects. Whether functional changes of GR are involved in the pathophysiology of cytokine-induced depression remains elusive. In the present study, the effects of both acute and chronic GR blockade on depressive-like behaviour and cytokine production induced by lipopolysaccharides (LPS), cytokine inducer, were investigated in rats. Acute or chronic blockade of GR was achieved by a single administration or repeated administrations, respectively, of the GR antagonist RU486 (RU). Behavioural measurements, including saccharin preference, locomotor activity, and immobility time, were assessed. The serum levels of proinflammatory cytokines (TNF alpha IL-1 beta, and IFN gamma) were determined by ELISA. The results showed that LPS induced significant but transient depressive-like behaviour. Repeated, but not single, administration of RU significantly enhanced and prolonged LPS-induced depressive-like behaviour and an increase in the serum production of TNF alpha and IFN gamma. These results indicate that the effective blockade of GR enhanced the depressive-like behaviour induced by cytokines. Findings from this study suggest that GR dysfunction may be an important contributing factor to the development of cytokine-related depression. These findings add to the growing evidence of mechanisms by which cytokines influence depression. (C) 2011 Elsevier Inc. All rights reserved.
关键词RU486 Glucocorticoid receptor Lipopolysaccharides Cytokines Depressive-like behaviour
学科领域Medical Psychology
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收录类别SCI
语种英语
项目资助者National Natural Science Foundation of China [30770718] ; Chinese Academy of Sciences [KSCX2-2-03, KSCX2-EW-J-8]
项目简介This research was supported by the grant (30770718) from the National Natural Science Foundation of China and the grants (KSCX2-2-03 and KSCX2-EW-J-8) from the Chinese Academy of Sciences.
WOS记录号WOS:000290463100014
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被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/8466
专题健康与遗传心理学研究室
通讯作者Lin, WJ (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, 4A Datun Rd, Beijing 100101, Peoples R China.
作者单位1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Psychol, Brain Behav Res Ctr, Beijing 100101, Peoples R China
3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
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Wang, Donglin,Lin, Wenjuan,Pan, Yuqin,et al. Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats[J]. BRAIN BEHAVIOR AND IMMUNITY,2011,25(4):706-714.
APA Wang, Donglin.,Lin, Wenjuan.,Pan, Yuqin.,Kuang, Xueying.,Qi, Xiaoli.,...&Lin, WJ .(2011).Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats.BRAIN BEHAVIOR AND IMMUNITY,25(4),706-714.
MLA Wang, Donglin,et al."Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats".BRAIN BEHAVIOR AND IMMUNITY 25.4(2011):706-714.
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