TNFα signaling in depression and anxiety:: Behavioral consequences of individual receptor targeting
TNFα signaling in depression and anxiety:: Behavioral consequences of individual receptor targeting
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DOI：
10.1016/j.biopsych.2005.10.013
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发表时间：
2006-05-01
影响因子：
10.6
通讯作者：
Duman, RS
中科院分区：
文献类型：
--
作者：
Simen, BB;Duman, CH;Duman, RS
背景资料：在重度抑郁症和其他几种精神疾病患者中发现TNF α和其他促炎细胞因子的血清水平升高。在啮齿类动物中，这些细胞因子产生通常被称为“疾病”行为的症状。”其中一些，包括减少进食和减少社交和探索行为，让人想起抑郁症患者中看到的那些。然而，由于急性注射促炎性细胞因子引起的不适，对这些效应的解释变得复杂。因此，目前尚不清楚是否有细胞因子参与抑郁症状的病因。方法：我们使用一组bebavioral测定来评估TNFR 1（-/-）和TNFR 2（-/-）小鼠的焦虑和抑郁样行为。我们发现TNRF 1或TNFR 2的缺失导致抗抑郁药-在强迫游泳试验中表现出类似的反应，并且与野生型同窝出生的小鼠相比，缺乏TNFR 2的小鼠在蔗糖饮用试验中表现出卧床反应。此外，TNFR 1的缺失导致恐惧条件反射减少。有没有差异，在焦虑测试中的行为为零mutant.Conclusions：这些结果是一致的假设，TNF α可以诱导抑郁样症状，即使在没有不适，并证明这两种受体亚型可以参与这种反应。
Background: Increased serum levels of TNF alpha and other pro-inflammatory cytokines have been found in patients with major depression and several other psychiatric conditions. In rodents, these cytokines produce symptoms commonly referred to as "sickness" behavioi," Some of these, including reduced feeding and decreased social and exploratory behavior, are reminiscent of those seen in depressed patients. Interpretation of these effects is complicated by the malaise caused by acute injections of pro-inflammatory cytokines, however. Thus, it is unclear whether cytokines are involved in the etiology of depressive symptoms.Methods: We used a panel of bebavioral assays to assess TNFR1(-/-) and TNFR2(-/-) mice for anxiety and depression-like bebaviors.Results: We show that deletion of either TNRF1 or TNFR2 leads to an antidepressant-like response in the forced swim test and that mice lacking TNFR2 demonstrate a bedonic response in a sucrose drinking test compared with wildtype littermates. In addition, deletion of TNFR1 leads to decreased fear conditioning. There were no differences in behavior in anxiety tests for either null mutant.Conclusions: These results are consistent with the hypothesis that TNF alpha can induce depression-like symptoms even in the absence of malaise and demonstrate that both receptor subtypes can be involved in this response.