Oligodendrogenesis and myelinogenesis during postnatal development effect of glatiramer acetate
Oligodendrogenesis and myelinogenesis during postnatal development effect of glatiramer acetate
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DOI：
10.1002/glia.22632
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发表时间：
2014-04-01
期刊：
影响因子：
6.2
通讯作者：
Aharoni, Rina
中科院分区：
文献类型：
--
作者：
From, Renana;Eilam, Raya;Aharoni, Rina
哺乳动物神经系统中的髓磷脂生成主要发生在出生后。醋酸格拉替雷 (GA) 是一种治疗多发性硬化症 (MS) 的药物，已被证明可以在 MS 和实验性自身免疫性脑脊髓炎 (EAE) 发炎的中枢神经系统中诱导免疫调节和神经保护。在这里，我们研究了 GA 是否可以在非病理条件下影响发育中的神经系统中的髓磷脂生成和少突胶质细胞生成。为此，我们研究了在出生后第 7-21 天每天注射 GA 的小鼠的髓鞘形成情况。免疫组织学和超微结构分析显示，出生后第 14 天，与注射 PBS 的同窝小鼠相比，注射 GA 的小鼠脊髓中有髓轴突的数量、环绕轴突的髓鞘厚度及其 g 比显着升高。在运动神经的外周腹侧根中也检测到有髓轴突的升高。 GA 还诱导轴突直径增加，这意味着对神经系统的整体发育有影响。祖少突胶质细胞的数量及其 BrdU 掺入以及成熟少突胶质细胞的显着升高表明 GA 的作用与少突胶质细胞成熟级联中增殖和分化的增加有关。此外，在注射 GA 的小鼠白质中发现胰岛素样生长因子 (IGF-1) 和脑源性神经营养因子 (BDNF) 升高。此外，在出生后第 21 天，注射 GA 的小鼠比其同窝小鼠在旋转棒测试中表现出功能优势。这些累积的发现证实了 GA 对少突胶质细胞生成和髓鞘形成的有益作用。 GLIA 2014；62：649-665
Myelinogenesis in the mammal nervous system occurs predominantly postnatally. Glatiramer acetate (GA), a drug for the treatment for multiple sclerosis (MS), has been shown to induce immunomodulation and neuroprotection in the inflamed CNS in MS and in experimental autoimmune encephalomyelitis (EAE). Here we investigated whether GA can affect myelinogenesis and oligodendrogenesis in the developing nervous system under nonpathological conditions. Towards this end we studied myelination in mice injected daily by GA, at postnatal Days 7-21. Immunohistological and ultrastructural analyses revealed significant elevation in the number of myelinated axons as well as in the thickness of the myelin encircling them and their resulting g-ratios, in spinal cords of GA-injected mice compared with their PBS-injected littermates, at postnatal Day 14. Elevation in myelinated axons was detected also in the peripheral ventral roots of the motor nerves. GA induced also an increase in axonal diameter, implying an effect on the overall development of the nervous system. A prominent elevation in the amount of progenitor oligodendrocytes and their BrdU incorporation, as well as in mature oligodendrocytes indicated that the effect of GA is linked to increased proliferation and differentiation along the oligodendroglial maturation cascade. In addition, elevation in insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) was found in the white matter of the GA-injected mice. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates at postnatal Day 21. These cumulative findings corroborate the beneficial effect of GA on oligodendrogenesis and myelination. GLIA 2014;62:649-665