Barrette Benoit, Vallières Nicolas, Dubé Marthe, Lacroix Steve
Department of Anatomy and Physiology, Laval University, Ste-Foy, Québec, Canada.
Mol Cell Neurosci. 2007 Apr;34(4):519-38. doi: 10.1016/j.mcn.2006.12.004. Epub 2007 Jan 17.
Although CNS neurons have the potential to regenerate their axons after injury, myelin debris carrying axon growth inhibitors rapidly induce growth cone collapse. Receptors (NgR1, NgR2) and coreceptors (LINGO-1, p75(NTR), TROY) for these inhibitors have been characterized and transduction pathways partially identified. However, little is known about the expression of these receptors in intact and lesioned supraspinal projection neurons. Using in situ hybridization, immunohistochemistry and neuronal tract-tracing, we found that NgR1, NgR2 and LINGO-1 are strongly expressed in several neuronal populations of the adult mouse brain projecting to the spinal cord, including neurons projecting through the corticospinal, rubrospinal, caerulospinal, reticulospinal, raphespinal and vestibulospinal tracts. As expected, p75(NTR) expression was restricted to neuronal descending pathways from the brainstem. TROY was absent from most brain regions and from all neuronal projection systems, suggesting that additional signal-transducing coreceptors exist. Qualitative and quantitative analyses revealed that brain expression for these receptors was not affected by a severe T10 spinal cord contusion.
尽管中枢神经系统神经元在损伤后有再生轴突的潜力,但携带轴突生长抑制剂的髓磷脂碎片会迅速导致生长锥塌陷。这些抑制剂的受体(NgR1、NgR2)和共受体(LINGO-1、p75(NTR)、TROY)已被鉴定,其转导途径也已部分明确。然而,对于这些受体在完整和损伤的脊髓上投射神经元中的表达情况,我们却知之甚少。通过原位杂交、免疫组织化学和神经束追踪技术,我们发现NgR1、NgR2和LINGO-1在成年小鼠大脑中投射至脊髓的多个神经元群体中强烈表达,这些神经元群体包括通过皮质脊髓束、红核脊髓束、蓝斑脊髓束、网状脊髓束、中缝脊髓束和前庭脊髓束投射的神经元。正如预期的那样,p75(NTR)的表达局限于来自脑干的神经元下行通路。大多数脑区和所有神经投射系统中均未检测到TROY的存在,这表明可能存在其他信号转导共受体。定性和定量分析显示,这些受体在脑中的表达不受严重的T10脊髓挫伤影响。