Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Neuroscience. 2013 Apr 16;236:31-46. doi: 10.1016/j.neuroscience.2012.12.063. Epub 2013 Jan 18.
In the spinal cord serotonin (5-HT) systems modulate the spinal network via various 5-HT receptors. Serotonin 2A receptor and serotonin 2C receptor (5-HT2A and 2C receptors) are likely the most important 5-HT receptors for enhancing the motoneuron excitability by facilitating the persistent inward current (PIC), and thus play an important role for the pathogenesis of spasticity after spinal cord injury. In conjunction with our 5-HT2A receptor study, using a same sacral spinal transection rat model we have in this study examined 5-HT2C receptor immunoreactivity (5-HT2CR-IR) changes at seven different time intervals after spinal injury. We found that 5-HT2CR-IR was widely distributed in different regions of the spinal gray matter and was predominantly located in the neuronal somata and their dendrites although it seemed also present in axonal fibers in the superficial dorsal horn. 5-HT2CR-IR in different regions of the spinal gray matter was seen to be increased at 14days after transection (with an average ∼1.3-fold higher than in sham-operated group) but did not reach a significant level until at 21days (∼1.4-fold). The increase sustained thereafter and a plateau level was reached at 45days (∼1.7-fold higher), a value similar as that at 60days. When 5-HT2CR-IR analysis was confined to the ventral horn motoneuron somata (including a proportion of proximal dendrites) a significant increase was not detected until 45days post-operation. 5-HT2CR upregulation in the spinal gray matter is confirmed with Western blot in the rats 60days post-operation. The time course of 5-HT2CR upregulation in the spinal gray matter and motoneurons was positively correlated with the development of tail spasticity (clinical scores). This indicates that 5-HT2CR is probably an important factor underlying this pathophysiological development by increasing the excitability of both motoneurons and interneurons.
在脊髓中，5-羟色胺（5-HT）系统通过各种 5-HT 受体来调节脊髓网络。5-羟色胺 2A 受体和 5-羟色胺 2C 受体（5-HT2A 和 5-HT2C 受体）可能是通过促进持续内向电流（PIC）增强运动神经元兴奋性的最重要的 5-HT 受体，因此在脊髓损伤后痉挛的发病机制中发挥重要作用。结合我们的 5-HT2A 受体研究，我们使用相同的骶骨脊髓横断大鼠模型，在这项研究中检查了脊髓损伤后 7 个不同时间间隔的 5-HT2C 受体免疫反应性（5-HT2CR-IR）变化。我们发现 5-HT2CR-IR 在脊髓灰质的不同区域广泛分布，主要位于神经元胞体及其树突中，尽管它似乎也存在于背角浅层的轴突纤维中。在横断后 14 天（与假手术组相比平均增加约 1.3 倍）观察到脊髓灰质不同区域的 5-HT2CR-IR 增加，但直到 21 天（增加约 1.4 倍）才达到显著水平。此后，增加持续，45 天达到平台水平（增加约 1.7 倍），与 60 天相似。当将 5-HT2CR-IR 分析仅限于腹角运动神经元胞体（包括一部分近端树突）时，直到术后 45 天才检测到显著增加。术后 60 天，大鼠脊髓组织的 Western blot 证实了脊髓灰质中 5-HT2CR 的上调。脊髓灰质和运动神经元中 5-HT2CR 的上调时间过程与尾巴痉挛的发展（临床评分）呈正相关。这表明 5-HT2CR 可能是通过增加运动神经元和中间神经元的兴奋性而成为这一病理生理发展的重要因素。
