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一种新型 BDNF 多态性与恒河猴早期逆境相互作用,影响血浆蛋白水平。

A novel BDNF polymorphism affects plasma protein levels in interaction with early adversity in rhesus macaques.

机构信息

Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.

出版信息

Psychoneuroendocrinology. 2011 Apr;36(3):372-9. doi: 10.1016/j.psyneuen.2010.10.019. Epub 2010 Dec 9.

Abstract

Early stressful events can increase vulnerability for psychopathology, although knowledge on the effectors is still limited. In this report we describe the characterization of a single nucleotide polymorphism (SNP) in rhesus macaques, which results in a Val to Met transition in the pro-BDNF domain, similar to a well described variant in the human gene. Further, we tested the hypothesis that peripheral levels of BDNF, which is involved in the response to stress and in the pathophysiology of anxiety and depression, might be differentially affected in a non-human primate model of early adverse rearing in a genotype-dependent manner. Males and females rhesus macaques reared either with their mothers (MR), in peer-only groups (PR), or in a "surrogate/peer-reared" (SPR) condition with limited peer interactions, were used as experimental subjects. BDNF levels were determined at baseline on postnatal days (PND) 14, 30 and 60 by means of specific ELISA procedure. Data indicate that BDNF levels were increased as a result of peer-rearing and that this increase was moderated by the presence of the SNP. Overall these data indicate that a SNP, which results in a Val to Met transition in the pro-BDNF domain, is present in rhesus macaques and is able to affect BDNF peripheral levels, thus making this primate model a fundamental tool to study gene by environment interactions involving the BDNF gene.

摘要

早期应激事件会增加精神病理学的易感性,尽管目前对其效应物的了解仍然有限。在本报告中,我们描述了恒河猴中一个单核苷酸多态性(SNP)的特征,该 SNP 导致前脑源性神经营养因子(pro-BDNF)结构域中的缬氨酸到蛋氨酸的转变,类似于人类基因中一种已被充分描述的变体。此外,我们还测试了这样一个假设,即外周血脑源性神经营养因子(BDNF)水平可能会以基因型依赖的方式,在早期不良养育的非人类灵长类动物模型中,受到不同的影响,BDNF 参与应激反应和焦虑与抑郁的病理生理学。我们使用了在母亲身边养育(MR)、在同伴中单独养育(PR)或在具有有限同伴互动的“替代/同伴养育”(SPR)条件下养育的雄性和雌性恒河猴作为实验对象。通过特定的 ELISA 程序,在产后第 14、30 和 60 天测定 BDNF 水平。数据表明,同伴养育会导致 BDNF 水平升高,而这种升高受到 SNP 的调节。总的来说,这些数据表明,一个 SNP 导致前脑源性神经营养因子(pro-BDNF)结构域中的缬氨酸到蛋氨酸的转变,存在于恒河猴中,并能够影响 BDNF 外周水平,从而使这种灵长类动物模型成为研究涉及 BDNF 基因的基因与环境相互作用的基本工具。

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