Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Brain Behav Immun. 2011 May;25(4):706-14. doi: 10.1016/j.bbi.2011.01.011. Epub 2011 Jan 27.
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 (TNFα, IL-1β, and IFNγ) 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 TNFα and IFNγ. 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.
尽管越来越多的证据支持细胞因子在抑郁症的病理生理学中的作用，但抑郁症的细胞因子假说仍存在争议。有人认为，协同作用的神经内分泌和免疫系统可能在疾病的发展和维持中发挥作用。糖皮质激素受体（GR）是发挥抗炎和细胞因子抑制作用的关键元素。GR 的功能变化是否参与细胞因子诱导的抑郁症的病理生理学仍然难以捉摸。在本研究中，我们研究了急性和慢性 GR 阻断对脂多糖（LPS）诱导的抑郁样行为和细胞因子产生的影响，LPS 是细胞因子诱导剂。通过单次给予 GR 拮抗剂 RU486（RU）或重复给予 RU 分别实现急性或慢性 GR 阻断。通过蔗糖偏好、运动活性和不动时间评估行为测量。通过 ELISA 测定促炎细胞因子（TNFα、IL-1β 和 IFNγ）的血清水平。结果表明，LPS 诱导了明显但短暂的抑郁样行为。重复给予 RU，但不是单次给予 RU，显著增强和延长了 LPS 诱导的抑郁样行为，并增加了 TNFα 和 IFNγ 的血清产生。这些结果表明，GR 的有效阻断增强了细胞因子诱导的抑郁样行为。本研究的结果表明，GR 功能障碍可能是细胞因子相关抑郁症发展的重要因素。这些发现增加了越来越多的关于细胞因子影响抑郁症的机制的证据。
