Jacobi Anne, Schmalz Anja, Bareyre Florence M
Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany.
Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
PLoS One. 2014 Feb 11;9(2):e88449. doi: 10.1371/journal.pone.0088449. eCollection 2014.
Spinal interneurons have emerged as crucial targets of supraspinal input during post-injury axonal remodelling. For example, lesioned corticospinal projections use propriospinal neurons as relay stations to form intraspinal detour circuits that circumvent the lesion site and contribute to functional recovery. While a number of the molecules that determine the formation of neuronal circuits in the developing nervous system have been identified, it is much less understood which of these cues are also expressed in the injured spinal cord and can thus guide growing collaterals and initiate synaptogenesis during circuit remodelling.
METHODOLOGY/PRINCIPAL FINDINGS: To address this question we characterized the expression profile of a number of guidance and synaptogenic molecules in the cervical spinal cord of healthy and spinal cord-injured mice by in situ hybridization. To assign the expression of these molecules to distinct populations of interneurons we labeled short and long propriospinal neurons by retrograde tracing and glycinergic neurons using a transgenically expressed fluorescent protein. Interestingly, we found that most of the molecules studied including members of slit-, semaphorin-, synCAM-, neuroligin- and ephrin- families as well as their receptors are also present in the adult CNS. While many of these molecules were abundantly expressed in all interneurons examined, some molecules including slits, semaphorin 7a, synCAM4 and neuroligin 1 showed preferential expression in propriospinal interneurons. Overall the expression pattern of guidance and synaptogenic molecules in the cervical spinal cord appeared to be stable over time and was not substantially altered following a midthoracic spinal cord injury.
Taken together, our study indicates that many of the guidance and synaptogenic cues that regulate neuronal circuit formation in development are also present in the adult CNS and therefore likely contribute to the remodelling of axonal connections in the injured spinal cord.
脊髓中间神经元已成为损伤后轴突重塑过程中脊髓上输入的关键靶点。例如，受损的皮质脊髓投射利用脊髓固有神经元作为中继站，形成绕过损伤部位的脊髓内迂回回路，促进功能恢复。虽然已经确定了许多在发育中的神经系统中决定神经元回路形成的分子，但对于这些信号中哪些也在损伤的脊髓中表达，从而能够在回路重塑过程中引导生长的侧支并启动突触形成，人们了解得还很少。
方法/主要发现：为了解决这个问题，我们通过原位杂交对健康小鼠和脊髓损伤小鼠颈脊髓中一些导向分子和突触形成分子的表达谱进行了表征。为了将这些分子的表达分配到不同的中间神经元群体，我们通过逆行追踪标记了短和长脊髓固有神经元，并使用转基因表达的荧光蛋白标记了甘氨酸能神经元。有趣的是，我们发现所研究的大多数分子，包括缝隙蛋白、信号素、突触细胞黏附分子、神经连接蛋白和 Ephrin 家族的成员及其受体，在成年中枢神经系统中也存在。虽然这些分子中的许多在所有检测的中间神经元中都大量表达，但一些分子，包括缝隙蛋白、信号素 7a、突触细胞黏附分子 4 和神经连接蛋白 1，在脊髓固有中间神经元中表现出优先表达。总体而言，颈脊髓中导向分子和突触形成分子的表达模式似乎随时间稳定，并且在胸段脊髓损伤后没有实质性改变。
综上所述，我们的研究表明，许多在发育过程中调节神经元回路形成的导向和突触形成信号在成年中枢神经系统中也存在，因此可能有助于损伤脊髓中轴突连接的重塑。
