The effects of prenatal stress on alpha4 beta2 and alpha7 hippocampal nicotinic acetylcholine receptor levels in adult offspring.
The effects of prenatal stress on alpha4 beta2 and alpha7 hippocampal nicotinic acetylcholine receptor levels in adult offspring.
复制标题
产前应激对成年后代α4β2和α7海马烟碱乙酰胆碱受体水平的影响。
DOI：
10.1002/dneu.22097
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发表时间：
2013
影响因子：
3
通讯作者：
Adams,CatherineE
中科院分区：
文献类型：
--
作者：
Schulz,KalynnM;Andrud,KristinM;Burke,MariaB;Pearson,JenniferN;Kreisler,AlisonD;Stevens,KarenE;Leonard,Sherry;Adams,CatherineE
人类的产前压力与后代的精神问题有关，如焦虑、抑郁和精神分裂症。这些相同的疾病也与神经元烟碱乙酰胆碱受体（nAChR）功能障碍有关。尽管已知产前应激暴露与后代精神疾病之间以及精神疾病与nAChR功能障碍之间存在关联，但尚不清楚产前应激暴露是否会影响神经元nAChR。因此，我们检验了母体应激改变成年后代海马α 4 β 2（α4β2 β）和α 7（α7 β）烟碱受体水平发育的假设。雌性Sprague-道利大鼠在妊娠最后一周每天经历两到三次不可预测的可变应激源。断奶时（21天），将产前应激（PS）和非应激（NS）母鼠的后代分配至同性别PS或NS组。在成年早期（56天），收集后代的大脑，并使用[125 I]-地棘蛙素（α4β2* 烟碱受体选择性）和[125 I]-α-银环蛇毒素（α-BTX; α7* 烟碱受体选择性）配体处理相邻切片进行定量放射自显影。我们发现PS显著增加了男性和女性海马α4β2* nAChRs在所有分析的子领域。相比之下，只有雌性动物显示出齿状回中PS诱导的α7* nAChR增加的趋势。有趣的是，NS雌性动物在CA 1区的laconosum moleculare中显示出显著的偏左偏侧化α7* nAChRs，而PS雌性动物则没有，这表明PS干扰了发育期间α7* nAChRs的正常偏侧化模式。总之，我们的研究结果表明，PS影响海马nAChRs的发展，这可能是PS暴露和神经精神疾病风险之间的重要联系。© 2013威利期刊公司.开发神经生物学73：806-814，2013年
Prenatal stress in humans is associated with psychiatric problems in offspring such as anxiety, depression, and schizophrenia. These same illnesses are also associated with neuronal nicotinic acetylcholine receptor (nAChR) dysfunction. Despite the known associations between prenatal stress exposure and offspring mental illness, and between mental illness and nAChR dysfunction, it is not known whether prenatal stress exposure impacts neuronal nAChRs. Thus, we tested the hypothesis that maternal stress alters the development of hippocampal alpha4 beta2 (α4β2∗) and alpha7 (α7∗) nicotinic receptor levels in adult offspring. Female Sprague‐Dawley rats experienced unpredictable variable stressors two to three times daily during the last week of gestation. At weaning (21 days) the offspring of prenatally stressed (PS) and nonstressed (NS) dams were assigned to same‐sex PS or NS groups. In young adulthood (56 days), the brains of offspring were collected and adjacent sections processed for quantitative autoradiography using [125I]‐epibatidine (α4β2* nicotinic receptor‐selective) and [125I]‐α‐bungarotoxin (α‐BTX; α7* nicotinic receptor‐selective) ligands. We found that PS significantly increased hippocampal α4β2* nAChRs of males and females in all subfields analyzed. In contrast, only females showed a trend toward PS‐induced increases in α7* nAChRs in the dentate gyrus. Interestingly, NS females displayed a significant left‐biased lateralization of α7* nAChRs in the laconosum moleculare of area CA1, whereas PS females did not, suggesting that PS interfered with normal lateralization patterns of α7* nAChRs during development. Taken together, our results suggest that PS impacts the development of hippocampal nAChRs, which may be an important link between PS exposure and risk for neuropsychiatric illness. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73:806–814, 2013