Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse.

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse.
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DOI:
10.1186/1471-2202-8-80
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发表时间:
2007-09-27
期刊:
影响因子:
2.4
通讯作者:
Anderson, Patrick N.
Anderson, Patrick N.
中科院分区:
医学4区
文献类型:
--
作者:
Hossain-Ibrahim, Mohammed K.;Rezajooi, Kia;Stallcup, William B.;Lieberman, Alexander R.;Anderson, Patrick N.

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硫酸软骨素蛋白多糖 NG2 可在体外阻断神经突生长,并被提议作为中枢神经系统轴突再生的主要抑制剂。尽管大量证据支持这一假设,但它受到最近发现的挑战,包括 NG2 在再生周围神经中的强表达。我们研究了不表达 NG2 的基因工程小鼠的三七总神经系统和中枢神经系统的轴突再生,以及性别和年龄匹配的野生型对照小鼠的轴突再生。在中枢神经系统中,我们使用 BDA 顺行追踪来研究脊髓损伤后的皮质脊髓束 (CST) 轴突,并使用 CT-HRP 跨节标记来追踪 DC 损伤和坐骨神经调理损伤后的上行感觉背柱 (DC) 轴突。这些纤维束损伤导致敲除小鼠和野生型小鼠的 CST 轴突或 DC 轴突进入或穿过损伤部位的能力没有差异。类似地,在背根损伤(伴随条件性损伤)后,转基因小鼠和野生型小鼠的大多数再生背根轴突都无法穿过背根进入区生长。坐骨神经损伤后,通过分析脚趾伸展反射和皮肤对冯弗雷毛发的敏感性来评估功能恢复。通过以下方式评估再生的解剖相关性:用 DiAsp 逆行标记再生背根神经节 (DRG) 细胞;使用 PGP 9.5 进行免疫染色,以可视化足底后爪的感觉神经支配;胫骨和指神经再生轴突的电子显微镜分析;并通过银胆碱酯酶组织化学研究运动终板神经支配。我们还通过评估胡须运动和角膜反射恢复所需的时间以及用 Fluorogold 和 DiAsp 逆行标记再生轴突来检查面神经损伤后再生的功能和解剖学相关性。解剖学或功能分析均未显示野生型小鼠和基因敲除小鼠之间存在显着差异。这些发现表明,NG2 不太可能是中枢神经系统损伤后轴突再生的主要抑制剂,而且,NG2 不太可能是周围神经损伤后再生或功能恢复所必需的。
The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve. We studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST) axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC) axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion), most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice. Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG) cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses revealed significant differences between wild-type and knockout mice. These findings show that NG2 is unlikely to be a major inhibitor of axonal regeneration after injury to the CNS, and, further, that NG2 is unlikely to be necessary for regeneration or functional recovery following peripheral nerve injury.
DOI: 10.1038/35012083
发表时间: 2000-05-11
期刊: NATURE
影响因子: 64.8
作者:
Bergles, DE;Roberts, JDB;Jahr, CE
通讯作者: Jahr, CE
DOI: 10.1023/a:1025751900356
发表时间: 2002-07-01
期刊: JOURNAL OF NEUROCYTOLOGY
影响因子: --
作者:
Butt, AM;Kiff, J;Berry, M
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DOI: 10.1002/glia.20060
发表时间: 2004-08-15
期刊: GLIA
影响因子: 6.2
作者:
Lin, SC;Bergles, DE
通讯作者: Bergles, DE
DOI: 10.1007/bf01257247
发表时间: 1990-08-01
期刊: JOURNAL OF NEUROCYTOLOGY
影响因子: --
作者:
MARTINI, R;SCHACHNER, M;FAISSNER, A
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DOI: 10.1002/ar.1090940210
发表时间: 1946-01-01
期刊: ANATOMICAL RECORD
影响因子: --
作者:
ABERCROMBIE, M
通讯作者: ABERCROMBIE, M