Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis.
Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis.
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DOI：
10.1002/jnr.23019
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发表时间：
2012-07
影响因子：
4.2
通讯作者：
Voskuhl, Rhonda R.
中科院分区：
文献类型：
--
作者：
MacKenzie-Graham, Allan J.;Rinek, Gilda A.;Avedisian, Andrea;Morales, Laurie B.;Umeda, Elizabeth;Boulat, Benoit;Jacobs, Russell E.;Toga, Arthur W.;Voskuhl, Rhonda R.
灰质萎缩与多发性硬化症 (MS) 的临床残疾具有重要相关性，许多治疗试验都将萎缩作为结果指标。实验性自身免疫性脑脊髓炎 (EAE) 是最常用的多发性硬化症动物模型，已显示萎缩发生。虽然雌激素治疗小鼠的 EAE 临床严重程度有所降低，但雌激素治疗是否可以减少 EAE 灰质萎缩仍不清楚。在这项研究中，患有 EAE 的小鼠接受雌激素受体 (ER)-α 配体或 ER-β 配体治疗，收集扩散张量图像 (DTI) 并进行神经病理学检查。与健康对照相比，DTI 显示媒介物处理的 EAE 小鼠的小脑灰质萎缩，但 ER-α 或 ER-β 配体处理的 EAE 小鼠则没有萎缩。神经病理学表明，在媒介物处理的 EAE 小鼠中，浦肯野细胞数量减少，而 ER 配体处理的 EAE 组均未显示出减少。这是 EAE 神经保护疗法的第一份报告，该疗法明确防止灰质萎缩，同时保留主要神经元细胞类型。在媒介物和 ER-β 配体处理的 EAE 小鼠中，小脑白质的分数各向异性 (FA) 降低，但在 ER-α 配体处理的 EAE 小鼠中则没有。在媒介物和 ER-β 配体处理的 EAE 小鼠中，炎症细胞浸润增加，但在 ER-α 配体处理的 EAE 小鼠中则没有增加。媒介物处理的 EAE 小鼠中髓磷脂染色减少，而 ER 配体处理组的髓磷脂染色均未减少。这与 EAE 中 FA 的减少作为小脑炎症的潜在生物标志物而不是髓鞘形成或轴突损伤一致。
Gray matter atrophy is an important correlate to clinical disability in multiple sclerosis (MS) and many treatment trials include atrophy as an outcome measure. Atrophy has been shown to occur in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. While the clinical severity of EAE is reduced in estrogen treated mice, it remains unknown whether estrogen treatment can reduce gray matter atrophy in EAE. In this study, mice with EAE were treated with either estrogen receptor (ER)-alpha ligand or ER-beta ligand, diffusion tensor images (DTI) were collected and neuropathology performed. DTI showed atrophy in the cerebellar gray matter of vehicle-treated EAE mice as compared to healthy controls, but not in ER-alpha or ER-beta ligand-treated EAE mice. Neuropathology demonstrated that Purkinje cell numbers were decreased in vehicle-treated EAE mice, while neither ER ligand-treated EAE groups showed a decrease. This is the first report of a neuroprotective therapy in EAE that unambiguously prevents gray matter atrophy while sparing a major neuronal cell type. Fractional anisotropy (FA) in the cerebellar white matter was decreased in vehicle-and ER-beta ligand-treated, but not in ER-alpha ligand-treated EAE mice. Inflammatory cell infiltration was increased in vehicle-and ER-beta ligand-treated, but not in ER-alpha ligand-treated EAE mice. Myelin staining was decreased in vehicle-treated EAE mice, and spared in both ER ligand-treated groups. This is consistent with decreased FA as a potential biomarker for inflammation rather than myelination or axonal damage in the cerebellum in EAE.
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影响因子：
3.3
作者：
GRUETTER, R
通讯作者：
GRUETTER, R
影响因子：
14.5
作者：
Edwards, SGM;Gong, QY;Blumhardt, LD
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Blumhardt, LD
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作者：
Fisher, E;Rudick, RA;Simonian, NA
通讯作者：
Simonian, NA
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作者：
Calabrese, Massimiliano;Mattisi, Irene;Gallo, Paolo
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Gallo, Paolo
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158.5
作者：
Confavreux, C;Hutchinson, M;Moreau, T
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Moreau, T