Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1
Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1
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DOI：
10.1038/npp.2014.304
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发表时间：
2015-03
影响因子：
7.6
通讯作者：
Xiao-Dun Yang;Xuemei Liao;A. Uribe-Mariño;Rui Liu;Xiao-Meng Xie;Jiao Jia;Yun-Ai Su;Ji‐Tao Li-Ji‐Tao
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文献类型：
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作者：
Xiao-Dun Yang;Xuemei Liao;A. Uribe-Mariño;Rui Liu;Xiao-Meng Xie;Jiao Jia;Yun-Ai Su;Ji‐Tao Li-Ji‐Tao
在出生后早期，环境影响在塑造新皮层的发展中起着关键作用，包括对工作记忆和目标导向行动至关重要的前额叶皮层（PFC）。在这个关键时期暴露于压力的经历可能会破坏PFC锥体神经元的发育，并损害相关神经回路的布线和功能。然而，早期生活压力对PFC发育和功能的影响的分子机制还不清楚。在这项研究中，我们发现，在出生后的第一周反复的压力暴露阻碍了树突状细胞的发育，在第II/III和V层锥体神经元的背侧无颗粒扣带皮层（ACd）和前边缘皮层（PL）的新生小鼠。出生后早期应激对结构可塑性的有害影响仅在ACd层V锥体神经元中持续到成年。最重要的是，在生命早期应激暴露期间，全身性antalarmin给药（20 μg/g体重）同时阻断促肾上腺皮质激素释放因子受体1（CRF 1）可预防ACd V层神经元中应激诱导的顶端树突回缩和棘丢失以及PFC依赖性认知任务的损伤。此外，树突状回退的幅度，特别是顶端分支的收缩，ACd层V神经元预测应激小鼠的认知缺陷的程度。我们的数据突出了出生后早期应激对前额叶锥体神经元结构可塑性的区域特异性影响，并表明CRF 1在调节早期应激诱导的前额叶异常中的关键作用。
During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF 1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF 1 in modulating early-life stress-induced prefrontal abnormalities.