PDF(Pubmed)
Abstract：
Circadian dysregulation involved in the pathophysiology of spinal cord injury (SCI). Modulation of circadian rhythms hold promise for the SCI treatment. Here, we aim to investigated the mechanism of olfactory ensheathing cells (OEC) in alleviating neuroinflammation via modulating clock gene expression in microglia. In this study, SCI rats were randomly divided into OEC group and vehicle group. At 1 day after the surgery, OECs were intravenously transplanted into OEC group SCI rat, while the rats in vehicle group received culture medium. After 7 days post of OEC transplantation, tissues were collected from the brain (prefrontal cortex, hypothalamus, spinal cord) for PCR, western blotting and immunohistochemistry (IHC) assay at zeitgeber time (ZT) 6, ZT 12, ZT 18, and ZT 24. The roles of OEC in modulating REV-ERBα in microglia were studied by experimental inhibition of gene expression and the co-culture experiment. In the vehicle group, IHC showed a significant increase of Iba-1 expression in the cerebral white matter and spinal cord compared with control group (P < 0.0001 for all comparisons). The expression of Iba-1 was significantly decreased (P < 0.0001 for all comparisons). In the OEC group, the expression of PER 1, PER 2, CLOCK, and REV-ERBα was in a rhythmical manner in both spinal cord and brain regions. SCI disrupted their typical rhythms. And OECs transplantation could modulate those dysregulations by upregulating REV-ERBα. In vitro study showed that OECs couldn\'t reduce the activation of REV-ERBα inhibited microglia. The intravenous transplantation of OECs can mediate cerebral and spinal microglia activation through upregulation REV-ERBα after SCI.
摘要：
昼夜节律失调涉及脊髓损伤（SCI）的病理生理学。昼夜节律的调节为SCI治疗带来了希望。这里,我们旨在研究嗅鞘细胞（OEC）通过调节小胶质细胞时钟基因表达减轻神经炎症的机制。在这项研究中,SCI年夜鼠随机分为OEC组和媒介物组。手术后1天,将OECs静脉移植到OEC组SCI大鼠中，而媒介物组的大鼠接受培养基。OEC移植后7天，从大脑收集组织(前额叶皮质，下丘脑,脊髓）用于PCR，在zeitgeber时间（ZT）6，ZT12，ZT18和ZT24进行蛋白质印迹和免疫组织化学（IHC）测定。通过实验抑制基因表达和共培养实验研究了OEC在调节小胶质细胞REV-ERBα中的作用。在车辆组中,IHC显示与对照组相比，Iba-1在脑白质和脊髓中的表达显着增加（所有比较均P<0.0001）。Iba-1的表达显著降低(所有比较P<0.0001)。在OEC组中，PER1，PER2，CLOCK，REV-ERBα在脊髓和脑区均有节奏。SCI打乱了他们典型的节奏。OECs移植可以通过上调REV-ERBα来调节这些失调。体外研究表明，OECs不能降低REV-ERBα抑制小胶质细胞的活化。OECs的静脉移植可以通过上调SCI后的REV-ERBα来介导脑和脊髓小胶质细胞的活化。
