The roles of neuronal and glial precursors in overcoming chondroitin sulfate proteoglycan inhibition.
The roles of neuronal and glial precursors in overcoming chondroitin sulfate proteoglycan inhibition.
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DOI：
10.1016/j.expneurol.2012.03.017
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发表时间：
2012-06
影响因子：
5.3
通讯作者：
Fischer, I.
中科院分区：
文献类型：
--
作者：
Ketschek, A. R.;Haas, C.;Gallo, G.;Fischer, I.
关键词：
轴突通过胶质瘢痕的主要抑制成分硫酸软骨素蛋白聚糖（CSPG）的延伸仍然是脊髓损伤（SCI）后再生的关键障碍。我们以前已经表明，由神经元和胶质细胞限制的前体（分别为NRP和GRP）组成的移植物促进损伤脊髓的再生和连接，然而，对这些前体在细胞水平上的性质知之甚少。我们现在报告，NRP衍生的神经元，背根神经节（DRG）神经元相比，有能力延长轴突和跨越从一个允许的基质（层粘连蛋白）抑制CSPG在体外。与DRG相比，来自NRP的神经元的生长锥表现出显著较低水平的CSPG受体蛋白酪氨酸磷酸酶σ（PTP σ）和白细胞共同抗原相关磷酸酶（LAR）。由相同细胞密度制备的GRP条件培养基不影响初级感觉神经元对CSPG的反应，证实了NRP衍生的神经元交叉到CSPG上的能力是内在决定的。然而，从高密度培养物中收集的GRP条件培养基增加了DRG轴突从LN跨越到CSPG的概率，并增加了在CSPG上延伸的DRG轴突的长度。总的来说，这些结果表明：（1）由于低水平的受体表达，来自NRP的神经元本质上对CSPG不敏感，以及（2）GRP分泌的高水平因子可以降低CSPG的抑制作用并促进轴突生长。这些观察结果提供了对NRPs和GRP在促进SCI后再生和修复中的特定作用的机制见解。
The extension of axons through the major inhibitory component of the glial scar, chondroitin sulfate proteoglycans (CSPG), remains a key obstacle for regeneration following spinal cord injury (SCI). We have previously shown that transplants composed of neuronal and glial restricted precursors (NRP and GRP respectively) promote regeneration and connectivity in the injured spinal cord, however, little is known about the properties of these precursors at a cellular level. We now report that NRP-derived neurons, in contrast to dorsal root ganglion (DRG) neurons, have the ability to extend axons and cross over from a permissive substratum (laminin) onto inhibitory CSPG in vitro. Growth cones of neurons derived from NRP, compared to DRG, exhibit significantly lower levels of the CSPG receptors protein tyrosine phosphatase sigma (PTPσ) and leukocyte common antigen-related phosphatase (LAR). GRP-conditioned medium prepared from the same cell densities did not affect the response of primary sensory neurons to CSPG confirming that the ability of NRP-derived neurons to cross onto CSPG is determined intrinsically. However, GRP-conditioned medium collected from high density cultures increased the probability of DRG axons to cross from LN onto CSPG and increased the length of DRG axons extending on CSPG. Collectively, these results suggest that (1) neurons derived from NRPs are intrinsically insensitive to CSPGs due to low levels of receptor expression, and (2) high levels of factors secreted by GRP can reduce the inhibitory effects of CSPG and promote axonal growth. These observations provide mechanistic insights into the specific roles of NRPs and GRPs in promoting regeneration and repair following SCI.
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影响因子：
4.2
作者：
Bonner, Joseph F.;Blesch, Armin;Neuhuber, Birgit;Fischer, Itzhak
通讯作者：
Fischer, Itzhak
影响因子：
5.3
作者：
Jones, LL;Margolis, RU;Tuszynski, MH
通讯作者：
Tuszynski, MH
影响因子：
5.3
作者：
Hynds, DL;Snow, DM
通讯作者：
Snow, DM
影响因子：
3.4
作者：
Properzi, F;Carulli, D;Fawcett, JW
通讯作者：
Fawcett, JW
DOI：
10.1126/science.1200840
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Coles CH;Shen Y;Tenney AP;Siebold C;Sutton GC;Lu W;Gallagher JT;Jones EY;Flanagan JG;Aricescu AR
通讯作者：
Aricescu AR