Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo
Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo
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DOI：
10.1073/pnas.1110444108
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发表时间：
2011-09-20
影响因子：
11.1
通讯作者：
Gan, Wen-Biao
中科院分区：
文献类型：
--
作者：
Liston, Conor;Gan, Wen-Biao
糖皮质激素是一个家族的激素，协调不同的生理过程，在应对压力。在成人大脑的固定组织研究中，长期暴露于糖皮质激素数周与树突萎缩和棘丢失有关，但目前尚不清楚糖皮质激素如何影响体内树突棘形成和消除的动态过程。此外，相对较少的研究已经检查了压力和糖皮质激素对脊髓在出生后和青少年时期，其特征是快速突触形成，然后延长突触修剪的影响。为了确定糖皮质激素是否以及在多大程度上调节树突棘的发育和可塑性，我们使用经颅双光子显微镜来跟踪发育和成年小鼠糖皮质激素治疗后体内树突棘的形成和消除。皮质酮，主要的小鼠糖皮质激素，有强大的剂量依赖性影响树突棘动力学，增加脊柱营业额在几个小时内在发展中的桶皮质。成人桶皮质表现出减少基线脊柱周转率，但这些利率也增强了皮质酮。类似的变化发生在多个皮质区，表明一个普遍的影响。然而，通过地塞米松抑制或皮质类固醇受体拮抗剂降低内源性糖皮质激素活性导致脊柱周转率大幅降低，而皮质酮替代可逆转前者。值得注意的是，我们发现慢性糖皮质激素过量导致生命早期建立的稳定脊柱的异常丢失。总之，这些发现确立了糖皮质激素在活皮质中树突棘的发育和维持中的关键作用。
Glucocorticoids are a family of hormones that coordinate diverse physiological processes in responding to stress. Prolonged glucocorticoid exposure over weeks has been linked to dendritic atrophy and spine loss in fixed tissue studies of adult brains, but it is unclear how glucocorticoids may affect the dynamic processes of dendritic spine formation and elimination in vivo. Furthermore, relatively few studies have examined the effects of stress and glucocorticoids on spines during the postnatal and adolescent period, which is characterized by rapid synaptogenesis followed by protracted synaptic pruning. To determine whether and to what extent glucocorticoids regulate dendritic spine development and plasticity, we used transcranial two-photon microscopy to track the formation and elimination of dendritic spines in vivo after treatment with glucocorticoids in developing and adult mice. Corticosterone, the principal murine glucocorticoid, had potent dose-dependent effects on dendritic spine dynamics, increasing spine turnover within several hours in the developing barrel cortex. The adult barrel cortex exhibited diminished baseline spine turnover rates, but these rates were also enhanced by corticosterone. Similar changes occurred in multiple cortical areas, suggesting a generalized effect. However, reducing endogenous glucocorticoid activity by dexamethasone suppression or corticosteroid receptor antagonists caused a substantial reduction in spine turnover rates, and the former was reversed by corticosterone replacement. Notably, we found that chronic glucocorticoid excess led to an abnormal loss of stable spines that were established early in life. Together, these findings establish a critical role for glucocorticoids in the development and maintenance of dendritic spines in the living cortex.