Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor
Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor
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DOI：
10.1017/s1461145712000168
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发表时间：
2013-03-01
影响因子：
4.8
通讯作者：
Vaidya, Vidita A.
中科院分区：
文献类型：
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作者：
Benekareddy, Madhurima;Nair, Amrita R.;Vaidya, Vidita A.
成年后暴露于压力和致幻剂会引起神经回路和情绪行为的持续改变。由应激和致幻剂暴露引起的结构和功能变化被认为涉及特定效应立即早期基因的转录改变。即早基因，活动调节的细胞内相关蛋白（Arc），是重要的活动和经验依赖的可塑性。我们试图研究是否通过脑源性神经营养因子（BDNF）的营养因子信号有助于新皮层的调节Arc mRNA在不同的刺激，如固定压力和致幻剂2，5-二甲氧基-4-碘苯丙胺（DOI）。急性暴露于固定应激或DOI诱导的新皮层内的Arc mRNA水平。BDNF输注到新皮层导致局部Arc转录本表达的强烈上调。此外，在诱导型BDNF敲除小鼠中，新皮质中的基线Arc mRNA表达显著降低，具有成年发病的前脑特异性BDNF损失。在诱导型BDNF敲除小鼠中，响应于急性制动应激或单次施用DOI的Arc mRNA水平的诱导显著减弱。两者合计，我们的研究结果暗示营养因子信号通过BDNF在皮质Arc mRNA表达的调节，无论是在基线条件下和以下的压力和致幻剂暴露。这些发现表明，通过BDNF调节Arc表达的可能性为在应激和致幻剂等刺激后观察到的结构和突触可塑性提供了分子底物。
Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytoskeletal-associated protein (Arc), is important for both activity and experience dependent plasticity. We sought to examine whether trophic factor signalling through brain-derived neurotrophic factor (BDNF) contributes to the neocortical regulation of Arc mRNA in response to distinct stimuli such as immobilization stress and the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Acute exposure to either immobilization stress or DOI induced Arc mRNA levels within the neocortex. BDNF infusion into the neocortex led to a robust up-regulation of local Arc transcript expression. Further, baseline Arc mRNA expression in the neocortex was significantly decreased in inducible BDNF knockout mice with an adult-onset, forebrain specific BDNF loss. The induction of Arc mRNA levels in response to both acute immobilization stress or a single administration of DOI was significantly attenuated in the inducible BDNF knockout mice. Taken together, our results implicate trophic factor signalling through BDNF in the regulation of cortical Arc mRNA expression, both under baseline conditions and following stress and hallucinogen exposure. These findings suggest the possibility that the regulation of Arc expression via BDNF provides a molecular substrate for the structural and synaptic plasticity observed following stimuli such as stress and hallucinogens.