Laboratory of Neurobiology, Scuola Normale Superiore, Pisa, Italy.
J Neurosci. 2013 Jul 10;33(28):11715-23. doi: 10.1523/JNEUROSCI.3541-12.2013.
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.
早期生活经历会影响大脑发育,从而导致个体之间对压力脆弱性和焦虑样行为的差异。在啮齿类动物中,高水平的母体照顾对后代的行为和应激反应有持久的积极影响;在丰富环境(EE)中或按摩后进行断奶饲养,可以抵消母体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 或按摩对大脑发育影响的关键介质。早期经验的丰富是否能对焦虑样行为产生持久影响,以及 IGF-1 是否参与这些影响尚不清楚。我们通过高架十字迷宫评估了对照成年大鼠和早期接受 EE 或按摩的成年大鼠的焦虑样行为。我们发现,EE 和按摩都减少了成年大鼠的焦虑样行为。在标准条件下饲养的幼鼠中进行早期 IGF-1 全身注射,可模拟 EE 和按摩的效果,减少成年鼠的焦虑样行为;在按摩和 EE 动物中阻断早期 IGF-1 作用,可防止按摩和 EE 的作用。在 EE 和 IGF-1 处理的动物中,我们在出生后第 12 天(P12)和第 60 天(P60)评估了海马体糖皮质激素受体(GRs)的表达,发现两种处理的 GRs 表达在 P60 时显著升高。这些结果表明,IGF-1 可能参与介导早期生活经历对成年期对压力的脆弱性/弹性的持久影响。