Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques
Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques
复制标题
DOI：
10.1111/j.1601-183x.2007.00383.x
复制
发表时间：
2008-06-01
影响因子：
2.5
通讯作者：
Capitanio, J. P.
中科院分区：
文献类型：
--
作者：
Kinnally, E. L.;Lyons, L. A.;Capitanio, J. P.
早期经验对基因-行为关联的调节作用已经得到了很好的表征。然而，允许这种缓和的分子事件还没有得到很好的理解。我们评估了早期经验和5-羟色胺转运体连锁启动子多态性（rh 5-HTTLPR）基因型对外周5-羟色胺转运体（5-HTT）调节的影响，以响应母亲/社会分离和搬迁压力源的恒河猴婴儿。我们进一步验证了这一假设，即通过饲养和/或基因型调节5-HTT调节是由糖皮质激素（GC）的可用性介导的。对53只幼儿园饲养（NR）或母亲饲养（MR）的幼年（3-4月龄）恒河猴进行rh 5-HTTLPR基因分型。在母亲或社会分离/搬迁后2.5小时内采集婴儿血样，并在5小时后再次采集。然后给婴儿服用地塞米松，合成GC，16.5小时后采血。5-从外周血单核细胞定量HTT RNA。在所有时间点测量血浆皮质醇。MR个体在母亲/社会分离期间显著上调5-HTT，而NR个体则没有。没有观察到皮质醇的伴随增加，但无论基因型/抚养组如何，地塞米松治疗都会刺激5-HTT表达，并且应激后样本中的5-HTT表达与所有时间点的血浆皮质醇水平相关。我们的数据表明，早期的经验产生了强烈的影响，5-HTT调节在婴儿恒河猴独立的rh 5-HTTLPR基因型的压力。我们还表明，GC可能会刺激5-HTT的表达，但可能存在更快的5-HTT的转录调节因子，在适当的功能的经验。
The moderating effect of early experience on gene-behavior associations has been well characterized. The molecular events that allow for such moderation are not well understood, however. We assessed the impact of early experience and serotonin transporter linked promoter polymorphism (rh5-HTTLPR) genotype on peripheral serotonin transporter (5-HTT) regulation in response to a maternal/social separation and relocation stressor in infant rhesus macaques. We further tested the hypothesis that modulation of 5-HTT regulation by rearing and/or genotype is mediated by glucocorticoid (GC) availability. Fifty-three infant (3-4 months of age) rhesus macaques that were either nursery reared (NR) or mother reared (MR) were genotyped for rh5-HTTLPR. Infants were blood sampled within 2.5 h of maternal or social separation/relocation and again 5 h later. Infants were then administered dexamethasone, a synthetic GC and blood sampled 16.5 h later. 5-HTT RNA was quantified from peripheral blood mononuclear cells. Plasma cortisol was measured at all time points. The MR individuals upregulated 5-HTT significantly during maternal/social separation, while NR individuals did not. Concomitant increases in cortisol were not observed, but dexamethasone treatment stimulated 5-HTT expression regardless of genotype/rearing group, and 5-HTT expression in the post-stressor sample was correlated with plasma cortisol levels at all time points. Our data indicate that early experience exerted a strong influence on 5-HTT regulation during a stressor in infant rhesus macaques independent of rh5-HTTLPR genotype. We also showed that GCs may stimulate 5-HTT expression but that there likely exist faster-acting transcriptional regulators of 5-HTT that are in place as a function of experience.