Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex.
Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex.
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DOI：
10.1002/cne.24027
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发表时间：
2016-12-15
影响因子：
2.5
通讯作者：
Radley, Jason J.
中科院分区：
文献类型：
--
作者：
Anderson, Rachel M.;Glanz, Ryan M.;Johnson, Shane B.;Miller, Mary M.;Romig-Martin, Sara A.;Radley, Jason J.
应激反应性下丘脑-垂体-肾上腺（HPA）轴在促进急性适应中起着核心作用，而慢性挑战后对生理和行为的不良影响可能是由于该系统的过度活跃。糖皮质激素（HPA激活的终产物）的升高通过靶向边缘皮层网络中整个神经元的同源受体以改变突触功能，在适应性和适应不良过程中发挥作用。由于以前的工作已经表明，慢性应激导致功能相关的退行性改变树突棘的形状和数量的锥体神经元内侧前额叶皮层（mPFC），在这里，我们研究的能力，持续增加循环皮质酮单独改变树突棘的形态和密度在这个地区。大鼠皮下植入皮质酮丸，以提供连续暴露于接近昼夜平均值或类固醇峰值的水平1、2或3周。选择mPFC边缘前区的锥体神经元进行细胞内荧光染料填充，然后进行高分辨率3D成像和树突分支和棘形态计量学分析。皮质酮暴露两周或两周以上的mPFC树突棘体积减少，而较高剂量的类固醇暴露导致顶端树突退缩和脊柱损失在同一细胞群中，薄脊柱亚型显示出最大程度的磨损。最后，注意到这些结构改变在3周洗脱期和相应的HPA昼夜节律恢复后持续存在。这些研究表明，肾上腺皮质功能的长期中断可能足以诱导持久的mPFC结构和功能的退行性改变。使用高分辨率共聚焦激光扫描显微镜，作者表明，长期升高皮质酮诱导树突棘形态的持续改变和大鼠内侧前额叶皮质的密度降低。该暗场图像显示了选择用于荧光黄（青色）细胞内染料填充的第2/3层前额叶锥体神经元。
The stress-responsive hypothalamo-pituitary-adrenal (HPA) axis plays a central role in promoting adaptations acutely, while adverse effects on physiology and behavior following chronic challenges may result from over-activity of this system. Elevations in glucocorticoids, the end-products of HPA activation, play roles in adaptive and maladaptive processes by targeting cognate receptors throughout neurons in limbic cortical networks to alter synaptic functioning. Since previous work has shown that chronic stress leads to functionally relevant regressive alterations in dendritic spine shape and number in pyramidal neurons in medial prefrontal cortex (mPFC), here we examine the capacity of sustained increases in circulating corticosterone alone to alter dendritic spine morphology and density in this region. Rats were implanted with subcutaneous corticosterone pellets to provide continuous exposure to levels approximating the circadian mean or peak of the steroid for 1, 2, or 3 weeks. Pyramidal neurons in prelimbic area of mPFC were selected for intracellular fluorescent dye-filling, followed by high-resolution 3D imaging and analysis of dendritic arborization and spine morphometry. Two or more weeks of corticosterone exposure decreased dendritic spine volume in mPFC, whereas higher dose exposure of the steroid resulted in apical dendritic retraction and spine loss in the same cell population, with thin spine subtypes showing the greatest degree of attrition. Finally, these structural alterations were noted to persist following a 3-week washout period and corresponding restoration of circadian HPA rhythmicity. These studies suggest that prolonged disruptions in adrenocortical functioning may be sufficient to induce enduring regressive structural and functional alterations in mPFC. Using high-resolution confocal laser-scanning microscopy, the authors show that prolonged elevations in corticosterone induce persistent alterations in dendritic spine morphology and decreased density in rat medial prefrontal cortex. This darkfield image shows layer 2/3 prefrontal pyramidal neurons selected for intracellular dye-filling with Lucifer Yellow (cyan).
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DOI：
10.1523/jneurosci.0759-10.2010
发表时间：
2010-05-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bloss EB;Janssen WG;McEwen BS;Morrison JH
通讯作者：
Morrison JH
DOI：
10.1073/pnas.0908563106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Hains, Avis Brennan;Vu, Mai Anh T.;Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
3.2
作者：
Crespo, Iris;Esther, Granell-Moreno;Resmini, Eugenia
通讯作者：
Resmini, Eugenia
影响因子：
5.3
作者：
Anderson, Rachel M.;Birnie, Andrew K.;Radley, Jason J.
通讯作者：
Radley, Jason J.
影响因子：
4.1
作者：
FELDMAN, S;CONFORTI, N
通讯作者：
CONFORTI, N