Severe Early Life Stress Hampers Spatial Learning and Neurogenesis, but Improves Hippocampal Synaptic Plasticity and Emotional Learning under High-Stress Conditions in Adulthood
Severe Early Life Stress Hampers Spatial Learning and Neurogenesis, but Improves Hippocampal Synaptic Plasticity and Emotional Learning under High-Stress Conditions in Adulthood
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DOI：
10.1523/jneurosci.0247-10.2010
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发表时间：
2010-05-12
影响因子：
5.3
通讯作者：
Krugers, Harm
中科院分区：
文献类型：
--
作者：
Oomen, Charlotte A.;Soeters, Heleen;Krugers, Harm
早期生活压力会增加日后患上压力相关疾病的风险。最近对大鼠的研究表明，轻度的早期生活压力，而不是整体不利，可能会编程海马体，使其最佳地适应生活后期的压力环境。在这里，我们测试了这种“适应性编程”的原则是否也适用于严重不利的早期生活条件，即，24小时的母亲剥夺（MD），母亲忽视的模型。在年轻的成年雄性大鼠出生后第3天MD，我们观察到成年海马神经发生的细胞增殖，细胞存活和神经元分化的水平降低。此外，成熟的齿状颗粒细胞表现出树突状形态的变化，这是最明显的树突树的近端部分。持久的结构变化，由于MD受损的水迷宫收购，但不影响长时程增强齿状回。重要的是，在高水平的应激激素皮质酮的存在下，即使是在MD动物的齿状回的长时程增强也得到了促进。除此之外，在高压力环境中的情境学习在MD大鼠中得到增强。这些形态学、电生理学和行为学的观察结果表明，即使是严重不利的早期生活环境也不会在以后的生活中演变成海马功能的整体受损。相反，生命早期的逆境可以使生物体在成年期高皮质类固醇水平的条件下表现最佳。
Early life stress increases the risk for developing stress-related pathologies later in life. Recent studies in rats suggest that mild early life stress, rather than being overall unfavorable, may program the hippocampus such that it is optimally adapted to a stressful context later in life. Here, we tested whether this principle of "adaptive programming" also holds under severely adverse early life conditions, i.e., 24 h of maternal deprivation (MD), a model for maternal neglect. In young adult male rats subjected to MD on postnatal day 3, we observed reduced levels of adult hippocampal neurogenesis as measured by cell proliferation, cell survival, and neuronal differentiation. Also, mature dentate granule cells showed a change in their dendritic morphology that was most noticeable in the proximal part of the dendritic tree. Lasting structural changes due to MD were paralleled by impaired water maze acquisition but did not affect long-term potentiation in the dentate gyrus. Importantly, in the presence of high levels of the stress hormone corticosterone, even long-term potentiation in the dentate gyrus of MD animals was facilitated. In addition to this, contextual learning in a high-stress environment was enhanced in MD rats. These morphological, electrophysiological, and behavioral observations show that even a severely adverse early life environment does not evolve into overall impaired hippocampal functionality later in life. Rather, adversity early in life can prepare the organism to perform optimally under conditions associated with high corticosteroid levels in adulthood.