A soluble Nogo receptor differentially affects plasticity of spinally projecting axons
A soluble Nogo receptor differentially affects plasticity of spinally projecting axons
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DOI：
10.1111/j.1460-9568.2004.03715.x
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Ramer, MS
中科院分区：
文献类型：
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作者：
MacDermid, VE;McPhail, LT;Ramer, MS
在中枢神经系统中，受损轴突的再生和完整轴突的萌发受到与Nogo受体(NGR)结合的髓鞘衍生分子的抑制。我们使用一种可溶性形式的NGR(SNGR)，作为人NGR胞外区的一种免疫球蛋白，来操纵背根切断后未损伤的初级传入和下行单胺能投射到大鼠脊髓的可塑性。四背根切断的大鼠接受鞘内SNGR或生理盐水治疗，或不治疗2周。单独切断5-羟色胺能轴突和少量表达酪氨酸羟化酶(TH)的轴突，而表达多巴胺-β-羟基酶(DbetaH)的轴突不受影响。人免疫球蛋白免疫组织化学显示，SNGR注入鞘内约300微米进入脊髓白质和灰质。不同的轴突群体对鞘内SNGR的反应不同：表达TH和表达DbetaH的轴突分别反应最强烈和最弱。5-羟色胺(5-HT)或5-羟色胺转运体(SERT)免疫组织化学标记5-羟色胺能轴突。有趣的是，与SERT阳性轴突密度相比，在生理盐水和SNGR处理的大鼠中，5-羟色胺的含量大幅增加，这表明5-羟色胺能轴突出芽并增加了它们的递质含量，以响应断根和SNGR处理。切断同侧神经根后，降钙素基因相关肽阳性轴突大量减少，SNGR仅增加对侧深层板层(III-V)的轴突密度。GAP-43免疫组织化学显示背根切断后轴突密度略有增加，而SNGR治疗后轴突密度进一步增加。这些结果揭示了髓鞘拮抗对不同的脊髓投射轴突群体的不同影响。
In the central nervous system, regeneration of injured axons and sprouting of intact axons are suppressed by myelin-derived molecules that bind to the Nogo receptor (NgR). We used a soluble form of the NgR (sNgR), constructed as an IgG of the human NgR extracellular domain, to manipulate plasticity of uninjured primary afferent and descending monoaminergic projections to the rat spinal cord following dorsal rhizotomy. Rats with quadruple dorsal rhizotomies were treated with intrathecal sNgR or saline, or were left untreated for 2 weeks. Rhizotomy alone resulted in sprouting of serotonergic axons and to a lesser extent, tyrosine-hydroxylase (TH)-expressing axons, while axons expressing dopamine-beta-hydroxylase (DbetaH) were unaffected. Human IgG immunohistochemistry revealed that sNgR infused into the intrathecal space penetrated approximately 300 mum into spinal white and grey matter. Separate axonal populations differed in their responses to intrathecal sNgR: TH-expressing and DbetaH-expressing axons responded most and least vigorously, respectively. Serotonergic axons were identified by serotonin (5-HT) or serotonin transporter (SERT) immunohistochemistry. Interestingly, a large increase in 5-HT compared to SERT-positive axons density in both saline and sNgR-treated rats indicated that serotonergic axons both sprouted and increased their transmitter content in response to rhizotomy and sNgR treatment. Calcitonin gene-related peptide-positive axons were largely depleted ipsilaterally by rhizotomy, and sNgR increased axon density only in deeper contralateral laminae (III-V). GAP-43 immunohistochemistry revealed a small increase in axon density following dorsal rhizotomy that was further augmented by sNgR treatment. These results reveal a differential effect of myelin antagonism on distinct populations of spinally projecting axons.