Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex-specific visceral hypersensitivity in offspring.
Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex-specific visceral hypersensitivity in offspring.
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DOI：
10.1111/nmo.12326
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发表时间：
2014-05
影响因子：
3.5
通讯作者：
Sarna SK
中科院分区：
文献类型：
--
作者：
Winston JH;Li Q;Sarna SK
肠易激综合征（IBS）是一种以腹痛为主要症状的异质性疾病。IBS的病因仍然未知。流行病学研究发现，这些患者的一个子集有不良早期生活事件的历史。我们测试了这一假设，慢性产前应激（CPS）表观遗传学增强脑源性神经营养因子（BDNF）在脊髓，以加重结肠直肠扩张（CRD）的差异在男性和女性后代的结肠敏感性。我们使用异型间歇性慢性应激（HeICS）协议在怀孕的母鼠从E11直到分娩。CPS诱导显着的内脏高敏感性（VHS）CRD在男性和女性后代。成年后代第二次暴露于HeICS加剧了VHS更大的女性后代，持续时间比男性后代。CPS上调BDNF在腰骶部背角的表达，这与VHS的恶化在女性，但在男性后代。BDNF的上调是由于RNA Pol II结合，组蛋白H3乙酰化和组蛋白去乙酰化酶1与BDNF核心启动子在雌性后代中的显着增加。其他慢性产前和新生儿应激方案的效果不如HeICS。内脏高敏感性的发展，这有助于间歇性腹痛的症状，是一个两步的过程，慢性子宫内的压力，其次是慢性压力在成年生活。这两个步骤的过程诱导加重和持续性结肠过敏的女性比男性后代。我们的临床前模型解释了IBS患者的几个临床特征。
Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdomen pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life events. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. CPS induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. CPS upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. The development of visceral hypersensitivity, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients.
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早期生活节目和神经发育障碍。
影响因子：
10.6
作者：
Bale, Tracy L.;Baram, Tallie Z.;Brown, Alan S.;Goldstein, Jill M.;Insel, Thomas R.;McCarthy, Margaret M.;Nemeroff, Charles B.;Reyes, Teresa M.;Simerly, Richard B.;Susser, Ezra S.;Nestler, Eric J.
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10.1152/ajpregu.00729.2005
发表时间：
2006-08-01
影响因子：
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作者：
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影响因子：
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作者：
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