Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder.
Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder.
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DOI：
10.1016/j.jpsychires.2011.01.013
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发表时间：
2011-07
影响因子：
4.8
通讯作者：
Diamond DM
中科院分区：
文献类型：
--
作者：
Roth TL;Zoladz PR;Sweatt JD;Diamond DM
脑源性神经营养因子（Bdnf）基因的表观遗传学改变与记忆、应激和神经精神疾病有关。在这里，我们研究了创伤后应激障碍（PTSD）的大鼠模型和BdnfDNA甲基化之间是否存在联系。成年雄性Sprague-Dawley大鼠给予心理社会应激，包括两次急性猫暴露和31天的日常社会不稳定。这些操作之前已经显示出在大鼠中产生的生理和行为后遗症与创伤后应激障碍患者中观察到的症状相当。然后，我们评估了BdnfDNA甲基化模式（外显子IV）和基因表达。我们发现，心理社会应激方案显著增加了背侧海马中的BdnfDNA甲基化，在背侧CA 1亚区检测到最强烈的超甲基化。相反，心理社会应激方案显著降低腹侧海马（CA 3）中的甲基化。内侧前额叶皮质或基底外侧杏仁核中未检测到BdnfDNA甲基化的变化。此外，背侧和腹侧CA 1区BdnfmRNA水平均降低。这些结果提供的证据表明，创伤性应激发生在成年期可以诱导CNS基因甲基化，特别是，支持的假设，表观遗传标记的Bdnf基因可能是海马功能障碍的基础，在创伤性应激反应。此外，这项工作为推测性的概念提供了支持，即改变的海马BdnfDNA甲基化是持续认知缺陷的细胞机制，这是PTSD病理生理学的突出特征。
Epigenetic alterations of the brain-derived neurotrophic factor (Bdnf) gene have been linked with memory, stress, and neuropsychiatric disorders. Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and BdnfDNA methylation. Adult male Sprague-Dawley rats were given psychosocial stress composed of two acute cat exposures in conjunction with 31 days of daily social instability. These manipulations have been shown previously to produce physiological and behavioral sequelae in rats that are comparable to symptoms observed in traumatized people with PTSD. We then assessed BdnfDNA methylation patterns (at exon IV) and gene expression. We have found here that the psychosocial stress regimen significantly increased BdnfDNA methylation in the dorsal hippocampus, with the most robust hypermethylation detected in the dorsal CA1 subregion. Conversely, the psychosocial stress regimen significantly decreased methylation in the ventral hippocampus (CA3). No changes in BdnfDNA methylation were detected in the medial prefrontal cortex or basolateral amygdala. In addition, there were decreased levels of BdnfmRNA in both the dorsal and ventral CA1. These results provide evidence that traumatic stress occurring in adulthood can induce CNS gene methylation, and specifically, support the hypothesis that epigenetic marking of the Bdnfgene may underlie hippocampal dysfunction in response to traumatic stress. Furthermore, this work provides support for the speculative notion that altered hippocampal BdnfDNA methylation is a cellular mechanism underlying the persistent cognitive deficits which are prominent features of the pathophysiology of PTSD.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
3.7
作者：
Collins A;Hill LE;Chandramohan Y;Whitcomb D;Droste SK;Reul JM
通讯作者：
Reul JM
影响因子：
8.2
作者：
BLANCHARD, RJ;BLANCHARD, DC;WEISS, SM
通讯作者：
WEISS, SM
DOI：
10.1073/pnas.0909359107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Choi, Dennis C.;Maguschak, Kimberly A.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
3.3
作者：
BOSCARINO, JA
通讯作者：
BOSCARINO, JA