Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression.
Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression.
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在两个慢性抑郁症模型中，去甲肾上腺素转运蛋白和药理学多样的抗抑郁药的敲除可以防止行为和脑神经营养蛋白改变。
DOI：
10.1111/j.1471-4159.2009.06345.x
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发表时间：
2009-10
影响因子：
4.7
通讯作者：
Bönisch H
中科院分区：
文献类型：
--
作者：
Haenisch B;Bilkei-Gorzo A;Caron MG;Bönisch H
神经营养因子的变化和大脑可塑性等多种因素被认为与抗抑郁药物（ADs）的作用有关。然而，在基于慢性应激的抑郁症小鼠模型中，行为和神经营养因子表达是否同时发生变化，以及这些变化是否能通过长期给予抗抑郁药物或产生抗抑郁样作用的基因操作（如去甲肾上腺素转运体（NET）基因敲除（KO））以类似的方式得到纠正或预防，仍不清楚。
在此我们表明，慢性束缚应激或社会挫败应激对行为产生类似的影响，并改变与抑郁症相关的大脑区域中神经营养因子的表达。慢性应激导致海马体和大脑皮层中脑源性神经营养因子（BDNF）、神经生长因子（NGF）和神经营养素-3（NT - 3）下调，以及纹状体区域中这些指标上调。在野生型小鼠中，同时长期给予五种药理作用不同的抗抑郁药物可以预防这些影响。相比之下，NETKO小鼠对慢性应激诱导的行为和脑神经营养因子表达的抑郁样变化具有抵抗力。因此，NETKO小鼠对慢性应激诱导的与抑郁症相关的行为和生化变化的抵抗力凸显了去甲肾上腺素能通路在维持情绪方面的重要性。此外，这些小鼠是研究抗抑郁行为的有用模型，它们可能有助于更深入地了解抗抑郁药物作用机制中涉及的下游靶点的识别。
Diverse factors such as changes in neurotrophins and brain plasticity have been proposed to be involved in the actions of antidepressant drugs (ADs). However, in mouse models of depression based on chronic stress, it is still unclear whether simultaneous changes in behavior and neurotrophin expression occur and whether these changes can be corrected or prevented comparably by chronic administration of ADs or genetic manipulations that produce antidepressant-like effects such as the knockout (KO) of the norepinephrine transporter (NET) gene. Here we show that chronic restraint or social defeat stress induce comparable effects on behavior and changes in the expression of neurotrophins in depression-related brain regions. Chronic stress caused down-regulation of BDNF, NGF and NT-3 in hippocampus and cerebral cortex and up-regulation of these targets in striatal regions. In wild-type mice, these effects could be prevented by concomitant chronic administration of five pharmacologically diverse ADs. In contrast, NETKO mice were resistant to stress-induced depressive-like changes in behavior and brain neurotrophin expression. Thus, the resistance of the NETKO mice to the stress-induced depression-associated behaviors and biochemical changes highlight the importance of noradrenergic pathways in the maintenance of mood. In addition, these mice represent a useful model to study depression-resistant behaviors, and they might help to provide deeper insights into the identification of downstream targets involved in the mechanisms of antidepressants.
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DOI：
10.1073/pnas.1034823100
发表时间：
2003-05-13
影响因子：
11.1
作者：
El Yacoubi, M;Bouali, S;Vaugeois, JM
通讯作者：
Vaugeois, JM
影响因子：
3.3
作者：
Haenisch, B.;Gilsbach, R.;Boenisch, H.
通讯作者：
Boenisch, H.
影响因子：
2.9
作者：
Balu, Darrick T.;Hoshaw, Brian A.;Lucki, Irwin
通讯作者：
Lucki, Irwin
DOI：
10.1017/s1461145707008383
发表时间：
2008-08-01
影响因子：
4.8
作者：
Guiard, Bruno P.;El Mansari, Mostafa;Blier, Pierre
通讯作者：
Blier, Pierre
影响因子：
4.7
作者：
BARABAN, JM;AGHAJANIAN, GK
通讯作者：
AGHAJANIAN, GK