Enriched Early Life Experiences Reduce Adult Anxiety-Like Behavior in Rats: A Role for Insulin-Like Growth Factor 1
Enriched Early Life Experiences Reduce Adult Anxiety-Like Behavior in Rats: A Role for Insulin-Like Growth Factor 1
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DOI：
10.1523/jneurosci.3541-12.2013
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发表时间：
2013-07-10
影响因子：
5.3
通讯作者：
Berardi, Nicoletta
中科院分区：
文献类型：
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作者：
Baldini, Sara;Restani, Laura;Berardi, Nicoletta
早期的生活经历会影响大脑发育，有助于形成压力脆弱性和焦虑行为的个体差异。在啮齿类动物中，高水平的母亲护理对后代的行为和应激反应有长期的积极影响;断奶后在丰富的环境（EE）中饲养或按摩抵消了母亲分离或产前应激源的负面影响。我们最近发现，胰岛素样生长因子1（IGF-1）是早期EE或按摩对大脑发育的关键介质。早期丰富的经验是否会对焦虑样行为产生持久的影响，以及IGF-1是否参与了这些影响尚不清楚。我们评估焦虑样行为的高架十字迷宫在控制成年大鼠和成年大鼠进行早期EE或按摩。我们发现EE和按摩都减少了成年人的焦虑行为。在标准条件下饲养的幼鼠中早期全身注射IGF-1可以模拟EE和按摩的效果，减少成年鼠的焦虑样行为;阻止按摩和EE动物的早期IGF-1作用可以防止按摩和EE效应。在EE和IGF-1治疗的动物中，我们评估了出生后第12天（P12）和P60时海马糖皮质激素受体（GR）的表达，发现两种治疗在P60时的GR表达显著较高。这些结果表明，IGF-1可能参与介导早期生活经历对成年人压力脆弱性/弹性的长期影响。
Early life experiences can affect brain development, contributing to shape interindividual differences in stress vulnerability and anxiety-like behavior. In rodents, high levels of maternal care have long-lasting positive effects on the behavior of the offspring and stress response; post-weaning rearing in an enriched environment (EE) or massage counteract the negative effects of maternal separation or prenatal stressors. We recently found that insulin-like growth factor 1(IGF-1) is a key mediator of early EE or massage on brain development. Whether early enrichment of experience can induce long-lasting effects on anxiety-like behavior and whether IGF-1 is involved in these effects is not known. We assessed anxiety-like behavior by means of the elevated plus maze in control adult rats and in adult rats subjected to early EE or to massage. We found that both EE and massage reduced adult anxiety-like behavior. Early IGF-1 systemic injections in rat pups reared in standard condition mimic the effects of EE and massage, reducing anxiety-like behavior in the adult; blocking early IGF-1 action in massaged and EE animals prevents massage and EE effects. In EE and IGF-1-treated animals, we assessed the hippocampal expression of glucocorticoid receptors (GRs) at postnatal day 12 (P12) and P60, finding a significantly higher GR expression at P60 for both treatments. These results suggest that IGF-1 could be involved in mediating the long-lasting effects of early life experiences on vulnerability/resilience to stress in adults.