CX3CR1 deficiency aggravates brain white matter injury and affects expression of the CD36/15LO/NR4A1 signal
CX3CR1 deficiency aggravates brain white matter injury and affects expression of the CD36/15LO/NR4A1 signal
复制标题
CX3CR1缺陷加重脑白质损伤并影响CD36/15LO/NR4A1信号的表达
DOI：
10.1016/j.bbrc.2021.02.053
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发表时间：
2021
影响因子：
3.1
通讯作者：
Jintao Yu
中科院分区：
文献类型：
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作者：
Wenzhu Wang;Jingbo Wang;Qing Tang;Xiwen Zhu;Rui Zhu;D;an Cui;Chunzhu Wei;Xinjie Liu;Xingxing Liu;Shanshan Ran;Yuzheng Pan;Jintao Yu
目的研究CX 3 CR 1对创伤性脑损伤（TBI）小鼠脑白色区损伤、神经功能、识别及CD 36/15 LO/NR 4A 1信号表达的影响。我们使用受控皮质撞击（CCI）建立TBI模型，并使用T2 wt MRI检测TBI病变。FA和DTI可以定量评价白色物质束的结构完整性。使用几种行为测试来研究神经功能;使用基于计算机的追踪系统来追踪和分析病灶周围脑区域中的小胶质细胞和星形胶质细胞的树突和细胞体。RT-PCR和western blot检测CX 3CL 1/CX 3CR 1轴对CD 36/15 LO/NR 4A 1信号的影响。结果脑外伤后第3天胼胝体区各向异性分数（FA）降低，CX 3CR 1GFP/GFP组平均损伤体积增加，与Cx 3Cr 1GFP/GFP组小鼠相比，Cx 3Cr 1GFP/+组和野生型组小鼠的神经功能缺损评分显著增加。在转角试验中，TBI诱导的前肢功能障碍比Cx 3Cr 11 GFP/+和野生型TBI小鼠更严重。我们在TBI后3天进行Y-迷宫测试，在TBI后28天进行NOR测试。与Cx 3Cr 1GFP/GFP; Cx 3Cr 1GFP/+相比，在Cx 3Cr 1GFP/+和野生型TBI小鼠中，在进入新臂的百分比降低中诱导了显著的TBI效应。与Cx 3Cr 1GFP/GFP相比，野生型小鼠在新物体中的探索时间减少。这两项行为测试表明，Cx 3Cr 1基因敲除增加了TBI对记忆的损害。在悬尾和强迫游泳试验中，三组之间无显著差异。Cx 3Cr 1GFP/GFP组伤后3天CD 36表达较其他3组明显增加。脑损伤后3d，TBI抑制NR 4A 1的表达。结论Cx 3Cr 1缺失可增强脑白色损伤。增加CD 36和15 LO的表达，增加NR 4A 1的表达。CX 3CR 1的缺失会影响神经功能的恢复。
ObjectiveTo study the effects of CX3CR1 on white matter injury, neurofunction, recognition, and expression of the CD36/15LO/NR4A1 signal in mice with traumatic brain injury (TBI).MethodsCX3CR1GFP/GFP, CX3CR1GFP/+and C57BL/6 male mice were randomly divided into 3 groups. We used a controlled cortical impact (CCI) to establish a TBI model and T2wt MRI to detect the TBI lesion. FA and DTI allowed for quantitative evaluation of the structural integrity of white matter tracts. Several behavior tests were used to investigate nerve function; a computer-based tracing system was used to trace and analyze dendrites and cell bodies of microglia and astrocytes in the peri-lesional brain areas. We also used RT-PCR and western blot to detect the effect of CX3CL1/CX3CR1 axis on CD36/15LO/NR4A1 signal.ResultsThe fractional anisotropy (FA) at the corpus callosum area of brain was decreased at 3 days post TBI, the average lesion volume CX3CR1GFP/GFPgroup was increased, and the neurologic deficit scores of mice of Cx3Cr1GFP/+and wild-type groups were significantly increased compared to Cx3Cr1GFP/GFPgroup mice. In the Corner turn test, TBI induced impairments in forelimb function that were more severe than Cx3Cr11GFP/+and wild-type TBI mice. We operated the Y-maze at 3 days post-TBI and the NOR test at 28 days after TBI. There was a significant TBI effect induced in decreased percentage entries into the novel arm in Cx3Cr1GFP/+and wild-type TBI mice, compared with Cx3Cr1GFP/GFP; Cx3Cr1GFP/+. Wild-type mice showed decreased exploration time in new objects compared with Cx3Cr1GFP/GFP. Those two behavior tests demonstrated that Cx3Cr1 knock-out increased the damage caused by TBI to memory. In the tail suspension and force swimming tests, there was no significant difference between those three groups. CD36 increased in Cx3Cr1GFP/GFPcompared with the other three groups at 3 days after TBI. TBI inhibited the expression of NR4A1 at 3 d after damage. Cx3Cr1 deficiency can induce high expression of 15LO, this was unaffected by TBI.ConclusionCX3CR1 deletion can enhance white matter injury. It increased the expression of CD36 and 15LO and increased expression of NR4A1. The lack of CX3CR1 can affect the recovery of nerve function.