Functional central nervous system myelin repair in an adult mouse model of demyelination caused by proteolipid protein overexpression.
Functional central nervous system myelin repair in an adult mouse model of demyelination caused by proteolipid protein overexpression.
复制标题
蛋白脂质蛋白过度表达引起的脱髓鞘成年小鼠模型中的功能性中枢神经系统髓鞘修复。
DOI：
10.1002/jnr.22334
复制
发表时间：
2010
影响因子：
4.2
通讯作者：
Ikenaka,K
中科院分区：
文献类型：
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作者：
Espinosa-Jeffrey,A;Hitoshi,S;Zhao,P;Awosika,O;Agbo,C;Olaniyan,E;Garcia,J;Valera,R;Thomassian,A;Chang-Wei,R;Yamaguchi,M;deVellis,J;Ikenaka,K
在过表达蛋白脂质蛋白基因的杂合转基因小鼠中研究了两种类型的干预措施，以使成人脱髓鞘中枢神经系统重新髓鞘化。1)营养因子“TS1”的混合物被导向神经祖细胞的内源性池的活化以增加脑中髓鞘形成少突胶质细胞（OL）的数量。2)一种组合方法，其中OL祖细胞与TS1共注射到显示后肢瘫痪的野生型和He4e转基因小鼠的胼胝体中。单次给药后评价这些小鼠的运动能力水平。数据显示，单次给予任何一种干预措施都具有相似的治疗效果，缓解了脱髓鞘症状，并导致后肢功能恢复。脑切片的组织学和免疫荧光检查显示广泛的髓鞘再生足以逆转转基因小鼠的后肢瘫痪。当在后肢瘫痪之前进行干预时，He4e小鼠能够行走长达1岁而不瘫痪。© 2010 Wiley利斯公司
Two types of interventions to remyelinate the adult demyelinated central nervous system were investigated in heterozygous transgenic mice overexpressing the proteolipid protein gene. 1) A cocktail of trophic factors, “TS1,” was directed toward the activation of the endogenous pool of neural progenitors to increase the number of myelinating oligodendrocytes (OL) in the brain. 2) A combinatorial approach in which OL progenitors were coinjected with TS1 into the corpus callosum of wild‐type and He4e transgenic mice that displayed hindlimb paralysis. The levels of locomotor ability in these mice were evaluated after a single treatment. The data showed that a single administration of either one of the interventions had similar therapeutic effects, alleviating the symptoms of demyelination and leading to the recovery of hindlimb function. Histological and immunofluorescent examination of brain sections showed extensive remyelination that was sufficient to reverse hindlimb paralysis in transgenic mice. When the interventions were administered prior to hindlimb paralysis, He4e mice were able to walk up to 1 year of age without paralysis. © 2010 Wiley‐Liss, Inc.