创伤性脑损伤小鼠海马和皮层NONO表达变化
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摘要
目的:探索创伤性脑损伤(TBI)后小鼠海马和皮层区不含POU结构的八聚体结合蛋白(NONO)表达变化。方法:重物打击法制作TBI小鼠模型,分为假手术组和TBI组,根据创伤后的时间TBI组又分为伤后6 h、24 h、3 d和7 d。Real time RT-PCR检测脑组织NONO mRNA表达,Western Blot和免疫组化检测脑组织NONO蛋白表达。结果:NONO在小鼠大脑皮层和海马区有较强表达,TBI后海马区NONO表达水平显著降低。结论:NONO在皮层和海马区均有表达,但是TBI后只有海马区NONO表达发生显著变化,实验结果为进一步研究NONO在TBI中的作用机制提供了基础。
Objective: To explore the expression of non-POU domain containing octamer-binding protein( NONO) in mouse hippocampus and cortex after traumatic brain injury( TBI). Methods: The TBI mouse model was induced by a weight-drop device. The mice were randomized into two groups,including Sham group and TBI group. The TBI group was sub-divided into 4 groups according to the time elapsed post injury( 6 h,24 h,3 d and 7 d after TBI). The mRNA level of NONO in hippocampus and cortex was detected by real-time RT-PCR,the expression and distribution of NONO protein was detected by Western Blot and immunohistochemistry. Results: NONO was strongly expressed in the hippocampus and cortex,while the expression of NONO in hippocampus was significantly decreased after TBI. Conclusion:Although NONO was expressed in both hippocampus and cortex,only the expression of NONO in hippocampus significantly reduced after TBI.The present results provided a basis for further study.
Objective: To explore the expression of non-POU domain containing octamer-binding protein( NONO) in mouse hippocampus and cortex after traumatic brain injury( TBI). Methods: The TBI mouse model was induced by a weight-drop device. The mice were randomized into two groups,including Sham group and TBI group. The TBI group was sub-divided into 4 groups according to the time elapsed post injury( 6 h,24 h,3 d and 7 d after TBI). The mRNA level of NONO in hippocampus and cortex was detected by real-time RT-PCR,the expression and distribution of NONO protein was detected by Western Blot and immunohistochemistry. Results: NONO was strongly expressed in the hippocampus and cortex,while the expression of NONO in hippocampus was significantly decreased after TBI. Conclusion:Although NONO was expressed in both hippocampus and cortex,only the expression of NONO in hippocampus significantly reduced after TBI.The present results provided a basis for further study.
引文
[1]钟世镇.关于创伤急救的几个问题[J].中华神经创伤外科电子杂志,2015,1(02):1-2. DOI:10. 3877/cma. j. issn. 2095-9141. 2015. 02. 001.
[2]王正国.创伤医学发展的思路[J].中华神经创伤外科电子杂志,2015,1(01):2-3. DOI:10. 3877/cma. j. issn. 2095-9141.2015. 01. 001.
[3]Carney N,Totten AM,O’Reilly C,et al. Guidelines for the management of severe traumatic brain injury,fourth edition[J]. Neurosurgery, 2017, 80(1):6-15. DOI:10. 1227/NEU.0000000000001432.
[4]Dawes AJ,Sacks GD,Cryer HG,et al. Compliance with evidencebased guidelines and interhospital variation in mortality for patients with severe traumatic brain injury[J]. JAMA Surg,2015,150(10):965-972. DOI:10. 1001/jamasurg. 2015. 1678.
[5] Dietrich WD,Bramlett HM. Therapeutic hypothermia and targeted temperature management for traumatic brain injury:Experimental and clinical experience[J]. Brain Circ,2017,3(4):186-198.DOI:10. 4103/bc. bc_28_17.
[6]Knott GJ,Bond CS,Fox AH. The DBHS proteins SFPQ,NONO and PSPC1:a multipurpose molecular scaffold[J]. Nucleic Acids Res,2016,44(9):3989-4004. DOI:10. 1093/nar/gkw271.
[7]Li D,Chen Y,Mei H,et al. Ets-1 promoter-associated noncoding RNA regulates the NONO/ERG/Ets-1 axis to drive gastric cancer progression[J]. Oncogene,2018,37(35):4871-4886. DOI:10. 1038/s41388-018-0302-4.
[8]Yang P,Chen T,Xu Z,et al. Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO[J]. Oncotarget,2016,7(27):42183-42194. DOI:10. 18632/oncotarget. 9741.
[9] Lahaye X,Gentili M,Silvin A,et al. NONO detects the nuclear HIV capsid to promote c GAS-mediated innate immune activation[J]. Cell,2018,175(2):488-501. DOI:10. 1016/j. cell.2018. 08. 062.
[10]Zibara K,Ballout N,Mondello S,et al. Combination of drug and stem cells neurotherapy:Potential interventions in neurotrauma and traumatic brain injury[J]. Neuropharmacology,2018. pii:S0028-3908(18)30694-4. DOI:10. 1016/j. neuropharm. 2018. 09. 032.
[11]Geddes DM,Laplaca MC,Cargill RN. Susceptibility of hippocampal neurons to mechanically induced injury[J]. Exp Neurol,2003,184(1):420-427.
[12]Amelio AL,Miraglia LJ,Conkright JJ,et al. A coactivator trap identifies NONO(p54nrb)as a component of the c AMP-signaling pathway[J]. Proc Natl Acad Sci USA,2007,104(51):20314-20319. DOI:10. 1073/pnas. 0707999105.
[13]Saura CA,Cardinaux JR. Emerging roles of CREB-regulated transcription coactivators in brain physiology and pathology[J]. Trends Neurosci,2017,40(12):720-733. DOI:10. 1016/j. tins. 2017.10. 002.
[14]Phu DT,Wallbach M,Depatie C,et al. Regμlation of the CREB coactivator TORC by the dual leucine zipper kinase at different levels[J]. Cell Signal,2011,23(2):344-353. DOI:10. 1016/j.cellsig. 2010. 10. 001.
[15]Mircsof D,Langou3t M,Rio M,et al. Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects[J].Nat Neurosci,2015,18(12):1731-1736. DOI:10. 1038/nn.4169.
[16]Elder GA. Update on TBI and cognitive impairment in military veterans[J]. Curr Neurol Neurosci Rep,2015,15(10):68. DOI:10. 1007/s11910-015-0591-8.
[17]Medaglia JD,Mcaleavey AA,Rostami S,et al. Modeling distinct imaging hemodynamics early after TBI:the relationship between signal amplitude and connectivity[J]. Brain Imaging Behav,2015,9(2):285-301. DOI:10. 1007/s11682-014-9306-z.
[2]王正国.创伤医学发展的思路[J].中华神经创伤外科电子杂志,2015,1(01):2-3. DOI:10. 3877/cma. j. issn. 2095-9141.2015. 01. 001.
[3]Carney N,Totten AM,O’Reilly C,et al. Guidelines for the management of severe traumatic brain injury,fourth edition[J]. Neurosurgery, 2017, 80(1):6-15. DOI:10. 1227/NEU.0000000000001432.
[4]Dawes AJ,Sacks GD,Cryer HG,et al. Compliance with evidencebased guidelines and interhospital variation in mortality for patients with severe traumatic brain injury[J]. JAMA Surg,2015,150(10):965-972. DOI:10. 1001/jamasurg. 2015. 1678.
[5] Dietrich WD,Bramlett HM. Therapeutic hypothermia and targeted temperature management for traumatic brain injury:Experimental and clinical experience[J]. Brain Circ,2017,3(4):186-198.DOI:10. 4103/bc. bc_28_17.
[6]Knott GJ,Bond CS,Fox AH. The DBHS proteins SFPQ,NONO and PSPC1:a multipurpose molecular scaffold[J]. Nucleic Acids Res,2016,44(9):3989-4004. DOI:10. 1093/nar/gkw271.
[7]Li D,Chen Y,Mei H,et al. Ets-1 promoter-associated noncoding RNA regulates the NONO/ERG/Ets-1 axis to drive gastric cancer progression[J]. Oncogene,2018,37(35):4871-4886. DOI:10. 1038/s41388-018-0302-4.
[8]Yang P,Chen T,Xu Z,et al. Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO[J]. Oncotarget,2016,7(27):42183-42194. DOI:10. 18632/oncotarget. 9741.
[9] Lahaye X,Gentili M,Silvin A,et al. NONO detects the nuclear HIV capsid to promote c GAS-mediated innate immune activation[J]. Cell,2018,175(2):488-501. DOI:10. 1016/j. cell.2018. 08. 062.
[10]Zibara K,Ballout N,Mondello S,et al. Combination of drug and stem cells neurotherapy:Potential interventions in neurotrauma and traumatic brain injury[J]. Neuropharmacology,2018. pii:S0028-3908(18)30694-4. DOI:10. 1016/j. neuropharm. 2018. 09. 032.
[11]Geddes DM,Laplaca MC,Cargill RN. Susceptibility of hippocampal neurons to mechanically induced injury[J]. Exp Neurol,2003,184(1):420-427.
[12]Amelio AL,Miraglia LJ,Conkright JJ,et al. A coactivator trap identifies NONO(p54nrb)as a component of the c AMP-signaling pathway[J]. Proc Natl Acad Sci USA,2007,104(51):20314-20319. DOI:10. 1073/pnas. 0707999105.
[13]Saura CA,Cardinaux JR. Emerging roles of CREB-regulated transcription coactivators in brain physiology and pathology[J]. Trends Neurosci,2017,40(12):720-733. DOI:10. 1016/j. tins. 2017.10. 002.
[14]Phu DT,Wallbach M,Depatie C,et al. Regμlation of the CREB coactivator TORC by the dual leucine zipper kinase at different levels[J]. Cell Signal,2011,23(2):344-353. DOI:10. 1016/j.cellsig. 2010. 10. 001.
[15]Mircsof D,Langou3t M,Rio M,et al. Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects[J].Nat Neurosci,2015,18(12):1731-1736. DOI:10. 1038/nn.4169.
[16]Elder GA. Update on TBI and cognitive impairment in military veterans[J]. Curr Neurol Neurosci Rep,2015,15(10):68. DOI:10. 1007/s11910-015-0591-8.
[17]Medaglia JD,Mcaleavey AA,Rostami S,et al. Modeling distinct imaging hemodynamics early after TBI:the relationship between signal amplitude and connectivity[J]. Brain Imaging Behav,2015,9(2):285-301. DOI:10. 1007/s11682-014-9306-z.