European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo, Italy.
Behav Brain Res. 2011 Feb 2;217(1):188-94. doi: 10.1016/j.bbr.2010.10.020. Epub 2010 Oct 23.
A number of studies have demonstrated that the common polymorphism in the serotonin transporter gene (5-HTT-LPR) moderates the increased risk for major depression seen in persons exposed to early adverse experiences. Several mouse models of this interaction have been recently established to investigate the increased vulnerability of individuals carrying the 5-HTT-LPR S allele to both early and adult life stressful events. Identifying the immediate effects of an adverse early environment on genetically susceptible individuals is critical to develop effective prevention of its long-term negative consequences of such an interaction. For this purpose we investigated molecular and neurochemical effects promoted by variable amount of maternal care in the brain of developing (postnatal day 10) wild type and heterozygous serotonin transporter knockout mice. Pups experiencing low level of maternal care showed increased levels of brain-derived neurotrophic factor (BDNF) messenger RNA within the hippocampus and primary somato-sensory cortex, and increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor binding in hippocampus in comparison with pups experiencing high level of maternal care. Strikingly, only heterozygous serotonin transporter knockout pups experiencing high maternal care showed increased hippocampal levels of serotonin and norepinephrine and decreased serotonin turnover compared to wild-type littermates. These findings support the hypothesis that maternal care affects the development of the hippocampus and primary somato-sensory cortex of individuals characterized by genetic variants of the serotonin transporter.
已有多项研究表明，5-羟色胺转运体基因（5-HTT-LPR）的常见多态性调节了暴露于早期不利环境的个体中重度抑郁症风险的增加。最近已经建立了几种该相互作用的小鼠模型，以研究携带 5-HTT-LPR S 等位基因的个体对早期和成年生活应激事件的易感性增加。确定不良早期环境对遗传易感个体的直接影响对于开发有效的预防措施至关重要，以防止这种相互作用产生长期的负面影响。为此，我们研究了不同数量的母体照顾对发育中（出生后第 10 天）野生型和杂合性 5-羟色胺转运体敲除小鼠大脑中的分子和神经化学效应。与经历高水平母体照顾的幼鼠相比，经历低水平母体照顾的幼鼠其海马体和初级躯体感觉皮层中的脑源性神经营养因子（BDNF）信使 RNA 水平升高，并且海马体中的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体结合增加。引人注目的是，只有经历高水平母体照顾的杂合性 5-羟色胺转运体敲除幼鼠表现出海马体中 5-羟色胺和去甲肾上腺素水平升高，以及 5-羟色胺周转率降低，与野生型同窝幼鼠相比。这些发现支持了这样一种假设，即母体照顾会影响具有 5-羟色胺转运体遗传变异个体的海马体和初级躯体感觉皮层的发育。
