Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex

Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex
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DOI:
10.1002/cne.21588
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发表时间:
2008-03-01
影响因子:
2.5
通讯作者:
Hof, Patrick R.
Hof, Patrick R.
中科院分区:
医学3区
文献类型:
--
作者:
Radley, Jason J.;Rocher, Anne B.;Hof, Patrick R.

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内侧前额叶皮层 (mPFC) 的解剖学改变与下丘脑垂体肾上腺 (HPA) 轴失调、应激激素水平改变以及与压力相关的精神疾病的精神症状有关。功能成像研究揭示了在这种情况下 mPFC 的损伤和收缩,这些发现与实验研究相一致,显示啮齿类动物反复受到压力后树突回缩和脊柱损失。在这里,我们通过利用快速数字化、三维重建和计算神经元几何特征的自动化方法,将这种表征扩展到重复应力如何影响 mPFC 中的树突棘形态。大鼠经受3周的每日约束应激(6小时/天)后进行灌注,并在背侧mPFC的II/III层锥体神经元中进行细胞内注射Lucifer Yellow。为了揭示所有方向角度的树突棘,使用基于 Rayburst 的自动化方法重建了树突片段的去卷积高分辨率共焦激光扫描显微镜图像堆栈并分析树突体积、表面积和长度(分别为 8,091 和 8,987 个树突用于控制和应力)。我们发现,重复的应力会导致平均树突棘体积和表面积总体下降,这在顶端的远端部分最为明显。树突场。此外,我们观察到刺数量的整体变化,表现为大刺的减少和小刺的增加。这些结果表明,在反复应激后,棘无法成熟和稳定,并可能对功能、受体表达和突触功效产生重大影响。 J.Comp。内罗尔。 507:1141-1150,2008。 (c) 2007 年 Wiley-Liss, Inc.
Anatomical alterations in the medial prefrontal cortex (mPFC) are associated with hypothalamopituitary adrenal (HPA) axis dysregulation, altered stress hormone levels, and psychiatric symptoms of stress-related mental illnesses. Functional imaging studies reveal impairment and shrinkage of the mPFC in such conditions, and these findings are paralleled by experimental studies showing dendritic retraction and spine loss following repeated stress in rodents. Here we extend this characterization to how repeated stress affects dendritic spine morphology in mPFC through the utilization of an automated approach that rapidly digitizes, reconstructs three dimensionally, and calculates geometric features of neurons. Rats were perfused after being subjected to 3 weeks of daily restraint stress (6 hours/day), and intracellular injections of Lucifer Yellow were made in layer II/III pyramidal neurons in the dorsal mPFC. To reveal spines in all angles of orientation, deconvolved high-resolution confocal laser scanning microscopy image stacks of dendritic segments were reconstructed and analyzed for spine volume, surface area, and length using a Rayburst-based automated approach (8,091 and 8,987 spines for control and stress, respectively). We found that repeated stress results in an overall decrease in mean dendritic spine volume and surface area, which was most pronounced in the distal portion of apical. dendritic fields. Moreover, we observed an overall shift in the population of spines, manifested by a reduction in large spines and an increase in small spines. These results suggest a failure of spines to mature and stabilize following repeated stress and are likely to have major repercussions on function, receptor expression, and synaptic efficacy. J. Comp. Neurol. 507: 1141-1150,2008. (c) 2007 Wiley-Liss, Inc.