Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.
Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.
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DOI：
10.1155/2007/26496
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发表时间：
2007
影响因子：
3.1
通讯作者：
Bramham CR
中科院分区：
文献类型：
--
作者：
Alme MN;Wibrand K;Dagestad G;Bramham CR
多项证据表明 BDNF 与压力诱发抑郁症的发病机制以及抗抑郁药物的延迟疗效有关。抗抑郁药诱导的 BDNF 信号上调被认为通过影响基因表达来促进适应性神经元可塑性，但 BDNF 下游的效应基因尚未确定。将 BDNF 局部输注到齿状回会诱导突触传递的长期增强 (BDNF-LTP)，这需要上调即刻早期基因 Arc。最近，我们鉴定了 5 个在 BDNF-LTP 过程中与 Arc 协同调节的基因（neuritin、Narp、TIEG1、Carp 和 Arl4d）。在这里，我们检查了抗抑郁治疗后这些基因在齿状回、海马体和前额皮质中的表达。我们发现，长期而不是急性的氟西汀给药会导致这些 BDNF-LTP 相关基因以大脑区域特异性模式上调。这些发现将抗抑郁治疗的慢性影响与 BDNF 诱导的突触可塑性的分子机制联系起来。
Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus induces a long-term potentiation (BDNF-LTP) of synaptic transmission that requires upregulation of the immediate early gene Arc. Recently, we identified five genes (neuritin, Narp, TIEG1, Carp, and Arl4d) that are coupregulated with Arc during BDNF-LTP. Here, we examined the expression of these genes in the dentate gyrus, hippocampus proper, and prefrontal cortex after antidepressant treatment. We show that chronic, but not acute, fluoxetine administration leads to upregulation of these BDNF-LTP-associated genes in a brain region-specific pattern. These findings link chronic effects of antidepressant treatment to molecular mechanisms underlying BDNF-induced synaptic plasticity.