Northport Veterans Affairs Medical Center, Northport, New York 11768, USA.
J Neurosci. 2010 Jun 9;30(23):7761-9. doi: 10.1523/JNEUROSCI.4659-09.2010.
Chronic unilateral hemisection (HX) of the adult rat spinal cord diminishes conduction through intact fibers in the ventrolateral funiculus (VLF) contralateral to HX. This is associated with a partial loss of myelination from fibers in the VLF (Arvanian et al., 2009). Here, we again measured conduction through the VLF using electrical stimulation while recording the resulting volley and synaptic potentials in target motoneurons. We found that intraspinal injection of chondroitinase-ABC, known to digest chondroitin sulfate proteoglycans (CSPGs), prevented the decline of axonal conduction through intact VLF fibers across from chronic T10 HX. Chondroitinase treatment was also associated with behavior suggestive of an improvement of locomotor function after chronic HX. To further study the role of CSPGs in axonal conduction, we injected three purified CSPGs, NG2 and neurocan, which increase in the vicinity of a spinal injury, and aggrecan, which decreases, into the lateral column of the uninjured cord at T10 in separate experiments. Intraspinal injection of NG2 acutely depressed axonal conduction through the injected region in a dose-dependent manner. Similar injections of saline, aggrecan, or neurocan had no significant effect. Immunofluorescence staining experiments revealed the presence of endogenous and exogenous NG2 at some nodes of Ranvier. These results identify a novel acute action of CSPGs on axonal conduction in the spinal cord and suggest that antagonism of proteoglycans reverses or prevents the decline of axonal conduction, in addition to stimulating axonal growth.
成年大鼠脊髓单侧半切（HX）会减少对侧腹外侧束（VLF）中完整纤维的传导。这与 VLF 中的纤维发生部分脱髓鞘有关（Arvanian 等人，2009）。在这里，我们再次使用电刺激测量 VLF 中的传导，同时记录目标运动神经元中的传入动作电位和突触电位。我们发现，软骨素酶 ABC 的鞘内注射（已知可消化软骨素硫酸蛋白聚糖 [CSPGs]）可防止慢性 T10 HX 后 VLF 中完整纤维的轴突传导下降。软骨素酶治疗也与慢性 HX 后运动功能改善的行为有关。为了进一步研究 CSPGs 在轴突传导中的作用，我们在单独的实验中将三种纯化的 CSPGs（NG2 和神经聚糖，它们在脊髓损伤附近增加，以及聚集素，它们减少）注入 T10 处未受伤的脊髓外侧柱。NG2 的鞘内注射以剂量依赖性方式急性抑制了注入区域的轴突传导。生理盐水、聚集素或神经聚糖的类似注射没有显著影响。免疫荧光染色实验显示存在内源性和外源性 NG2 在一些Ranvier 结处。这些结果确定了 CSPGs 对脊髓轴突传导的一种新的急性作用，并表明蛋白聚糖的拮抗作用除了刺激轴突生长外，还可以逆转或防止轴突传导的下降。
