Fuller David D, Baker-Herman Tracy L, Golder Francis J, Doperalski Nicholas J, Watters Jyoti J, Mitchell Gordon S
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
J Neurotrauma. 2005 Feb;22(2):203-13. doi: 10.1089/neu.2005.22.203.
Following chronic C2 spinal hemisection (C2HS), crossed spinal pathways to phrenic motoneurons exhibit a slow, spontaneous increase in efficacy by a serotonin (5-HT)-dependent mechanism associated with 5-HT2A receptor activation. Further, the spontaneous appearance of cross-phrenic activity following C2HS is accelerated and enhanced by exposure to chronic intermittent hypoxia (CIH). We hypothesized that chronic C2HS would increase 5-HT and 5-HT2A receptor expression in ventral cervical spinal segments containing phrenic motoneurons. In addition, we hypothesized that CIH exposure would further increase 5-HT and 5-HT2A receptor density in this region. Control, sham-operated, and C2HS Sprague-Dawley rats were studied following normoxia or CIH (11% O2-air; 5-min intervals; nights 7-14 post-surgery). At 2 weeks post-surgery, ventral spinal gray matter extending from C4 and C5 was isolated ipsilateral and contralateral to C2HS. Neither C2HS nor CIH altered 5-HT concentration measured with an ELISA on either side of the spinal cord. However, 5-HT2A receptor expression assessed with immunoblots increased in ipsilateral gray matter following C2HS, an effect independent of CIH. Immunocytochemistry revealed increased 5-HT2A receptor expression on identified phrenic motoneurons (p<0.05), as well as in the surrounding gray matter. Contralateral to injury, 5-HT2A receptor expression was elevated in CIH, but not normoxic C2HS rats (p<0.05). Our data are consistent with the hypothesis that spontaneous increase in 5-HT2A receptor expression on or near phrenic motoneurons contributes to strengthened crossed-spinal synaptic pathways to phrenic motoneurons following C2HS.
在慢性C2脊髓半横断（C2HS）后，通向膈运动神经元的交叉脊髓通路通过与5-羟色胺（5-HT）依赖性机制相关的5-HT2A受体激活，表现出缓慢、自发的效能增加。此外，C2HS后交叉膈神经活动的自发出现会因暴露于慢性间歇性缺氧（CIH）而加速和增强。我们假设慢性C2HS会增加含有膈运动神经元的颈段腹侧脊髓节段中5-HT和5-HT2A受体的表达。此外，我们假设暴露于CIH会进一步增加该区域中5-HT和5-HT2A受体的密度。在常氧或CIH（11% O2-空气；5分钟间隔；术后第7 - 14晚）条件下，对对照、假手术和C2HS的Sprague-Dawley大鼠进行研究。术后2周，分离C2HS同侧和对侧从C4和C5延伸的脊髓腹侧灰质。C2HS和CIH均未改变通过酶联免疫吸附测定法在脊髓两侧测得的5-HT浓度。然而，用免疫印迹法评估的5-HT2A受体表达在C2HS后的同侧灰质中增加，这一效应与CIH无关。免疫细胞化学显示，在已识别的膈运动神经元（p<0.05）以及周围灰质中，5-HT2A受体表达增加。在损伤对侧，CIH条件下5-HT2A受体表达升高，但常氧C2HS大鼠中未升高（p<0.05）。我们的数据与以下假设一致，即膈运动神经元上或其附近5-HT2A受体表达的自发增加有助于C2HS后通向膈运动神经元的交叉脊髓突触通路增强。
