Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.
Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.
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DOI：
10.1002/glia.22736
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发表时间：
2015-01
期刊：
影响因子：
6.2
通讯作者：
Sitruk-Ware, Regine
中科院分区：
文献类型：
--
作者：
El-Etr, Martine;Rame, Marion;Boucher, Celine;Ghoumari, Abdel. M.;Kumar, Narender;Liere, Philippe;Pianos, Antoine;Schumacher, Michael;Sitruk-Ware, Regine
多发性硬化症主要影响女性，包括髓鞘的间歇性或慢性损伤、局灶性炎症和轴突变性。目前的治疗方法仅限于免疫调节剂和抗炎药物，但没有有效的治疗方法来刺激内源性髓磷脂修复能力。在脱髓鞘动物模型中，黄体酮和合成黄体酮已被证明可减轻髓磷脂损失，减轻临床症状严重程度，调节炎症反应，并部分逆转年龄依赖性的髓鞘再生衰退。此外，黄体酮已被证明在小脑切片的器官型培养中促进髓磷脂的形成。在本研究中，我们发现黄体酮和合成的19-非黄体酮衍生物Nestorone®可促进铜酮喂养12周的雌性小鼠严重慢性脱髓鞘损伤的修复。孕酮和奈斯托酮可增加NG2+少突胶质细胞祖细胞和CA II+成熟少突胶质细胞的密度，促进髓鞘碱性蛋白(MBP)-和蛋白脂质蛋白(PLP)-免疫反应性髓鞘的形成。然而，尽管铜酮对胼胝体脱髓鞘的影响不如大脑皮层明显，但胼胝体的脱髓鞘出现得更早。黄体酮的再髓鞘作用是依赖于黄体酮受体（PR）的，因为在PR敲除小鼠中不存在。黄体酮和奈斯托酮也降低（但不抑制）神经炎症反应，特别是星形胶质细胞和小胶质细胞的激活。因此，一些孕激素是促进髓磷脂再生的有希望的治疗候选者。
Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation and axonal degeneration. Current therapies are limited to immunomodulators and anti-inflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2+ oligodendrocyte progenitor cells and CA II+ mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.
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影响因子：
3.2
作者：
Giatti, S.;Caruso, D.;Melcangi, R. C.
通讯作者：
Melcangi, R. C.
影响因子：
56.9
作者：
KOENIG, HL;SCHUMACHER, M;BAULIEU, EE
通讯作者：
BAULIEU, EE
DOI：
10.1016/s0006-291x(02)00191-2
发表时间：
2002-04-26
影响因子：
3.1
作者：
Bastida, CM;Tejada, F;Peñafiel, R
通讯作者：
Peñafiel, R
影响因子：
2.9
作者：
BLAUSTEIN, JD;TURCOTTE, JC
通讯作者：
TURCOTTE, JC
影响因子：
5.3
作者：
Harsan, Laura-Adela;Steibel, Jerome;Ghandour, M. Said
通讯作者：
Ghandour, M. Said