期刊论文详细信息
BMC Neuroscience
Time-specific microRNA changes during spinal motoneuron degeneration in adult rats following unilateral brachial plexus root avulsion: ipsilateral vs. contralateral changes
Li-Hua Zhou1  Hao-Xuan Luo1  Fa-Huan Song1  Xiao Cheng1  Ying-Qin Li2  Rao Fu1  Ze-Min Ling1  Ying Tang1 
[1] Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Guangzhou 510080, P.R. China;Department of Radiology, The Fifth Affiliated Hospital, Sun Yat-sen University, No. 74 Zhongshan Road 2, Guangzhou 510080, P.R. China
关键词: Calpain 2;    ATF-3;    c-jun;    nNOS;    Inflammatory response;    Microarray;    MicroRNA;    Brachial root avulsion;   
Others  :  1091584
DOI  :  10.1186/1471-2202-15-92
 received in 2014-01-20, accepted in 2014-07-16,  发布年份 2014
PDF
【 摘 要 】

Background

Spinal root avulsion induces multiple pathophysiological events consisting of altered levels of specific genes and proteins related to inflammation, apoptosis, and oxidative stress, which collectively result in the death of the affected motoneurons. Recent studies have demonstrated that the gene changes involved in spinal cord injury can be regulated by microRNAs, which are a class of short non-coding RNA molecules that repress target mRNAs post-transcriptionally. With consideration for the time course of the avulsion-induced gene expression patterns within dying motoneurons, we employed microarray analysis to determine whether and how microRNAs are involved in the changes of gene expression induced by pathophysiological events in spinal cord motoneurons.

Results

The expression of a total of 3,361 miRNAs in the spinal cord of adult rats was identified. Unilateral root-avulsion resulted in significant alterations in miRNA expression. In the ipsilateral half compared to the contralateral half of the spinal cord, on the 3rd day after the injury, 55 miRNAs were upregulated, and 24 were downregulated, and on the 14th day after the injury, 36 miRNAs were upregulated, and 23 were downregulated. The upregulation of miR-146b-5p and miR-31a-3p and the downregulation of miR-324-3p and miR-484 were observed. Eleven of the miRNAs, including miR-21-5p, demonstrated a sustained increase; however, only miR-466c-3p presented a sustained decrease 3 and 14 days after the injury. More interestingly, 4 of the miRNAs, including miR-18a, were upregulated on the 3rd day but were downregulated on the 14th day after injury.

Some of these miRNAs target inflammatory-response genes in the early stage of injury, and others target neurotransmitter transport genes in the intermediate stages of injury. The altered miRNA expression pattern suggests that the MAPK and calcium signaling pathways are consistently involved in the injury response.

Conclusions

This analysis may facilitate the understanding of the time-specific altered expression of a large set of microRNAs in the spinal cord after brachial root avulsion.

【 授权许可】

   
2014 Tang et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150128172935965.pdf 2325KB PDF download
Figure 6. 165KB Image download
Figure 5. 129KB Image download
Figure 4. 48KB Image download
Figure 3. 36KB Image download
Figure 2. 122KB Image download
Figure 1. 115KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]Wang LL, Zhao XC, Yan LF, Wang YQ, Cheng X, Fu R, Zhou LH: C-jun phosphorylation contributes to down regulation of neuronal nitric oxide synthase protein and motoneurons death in injured spinal cords following root-avulsion of the brachial plexus. Neuroscience 2011, 189:397-407.
  • [2]Zhao XC, Wang LL, Wang YQ, Song FH, Li YQ, Fu R, Zheng WH, Wu W, Zhou LH: Activation of phospholipase-Cgamma and protein kinase C signal pathways helps the survival of spinal motoneurons injured by root avulsion. J Neurochem 2012, 121(3):362-372.
  • [3]Cheng X, Fu R, Gao M, Liu S, Li YQ, Song FH, Bruce IC, Zhou LH, Wu W: Intrathecal application of short interfering RNA knocks down c-jun expression and augments spinal motoneuron death after root avulsion in adult rats. Neuroscience 2013, 241:268-279.
  • [4]Juhila J, Sipila T, Icay K, Nicorici D, Ellonen P, Kallio A, Korpelainen E, Greco D, Hovatta I: MicroRNA expression profiling reveals miRNA families regulating specific biological pathways in mouse frontal cortex and hippocampus. PLoS One 2011, 6(6):e21495.
  • [5]Wang J, Yan L, Zhao X, Wu W, Zhou LH: The diversity of nNOS gene expression in avulsion-injured spinal motoneurons among laboratory rodents. Nitric Oxide 2010, 22(1):37-42.
  • [6]Du T, Zamore PD: microPrimer: the biogenesis and function of microRNA. Development 2005, 132(21):4645-4652.
  • [7]Carthew RW, Sontheimer EJ: Origins and Mechanisms of miRNAs and siRNAs. Cell 2009, 136(4):642-655.
  • [8]Bhalala OG, Srikanth M, Kessler JA: The emerging roles of microRNAs in CNS injuries. Nat Rev Neurol 2013, 9(6):328-339.
  • [9]Lee CT, Risom T, Strauss WM: Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny. DNA Cell Biol 2007, 26(4):209-218.
  • [10]Haramati S, Chapnik E, Sztainberg Y, Eilam R, Zwang R, Gershoni N, McGlinn E, Heiser PW, Wills AM, Wirguin I, Rubin LL, Misawa H, Tabin CJ, Brown R Jr, Chen A, Hornstein E: miRNA malfunction causes spinal motor neuron disease. Proc Natl Acad Sci U S A 2010, 107(29):13111-13116.
  • [11]Nelson PT, Wang WX, Rajeev BW: MicroRNAs (miRNAs) in neurodegenerative diseases. Brain Pathol 2008, 18(1):130-138.
  • [12]Campos-Melo D, Droppelmann CA, He Z, Volkening K, Strong MJ: Altered microRNA expression profile in Amyotrophic Lateral Sclerosis: a role in the regulation of NFL mRNA levels. Mol Brain 2013, 6:26.
  • [13]Zhou LH, Wu W: Survival of injured spinal motoneurons in adult rat upon treatment with glial cell line-derived neurotrophic factor at 2 weeks but not at 4 weeks after root avulsion. J Neurotrauma 2006, 23(6):920-927.
  • [14]Risling M, Ochsman T, Carlstedt T, Linda H, Plantman S, Rostami E, Angeria M, Skold MK: On acute gene expression changes after ventral root replantation. Front Neurol 2011, 1:159.
  • [15]Wu W, Li Y, Schinco FP: Expression of c-jun and neuronal nitric oxide synthase in rat spinal motoneurons following axonal injury. Neurosci Lett 1994, 179(1–2):157-161.
  • [16]Wu W, Li L, Yick LW, Chai H, Xie Y, Yang Y, Prevette DM, Oppenheim RW: GDNF and BDNF alter the expression of neuronal NOS, c-Jun, and p75 and prevent motoneuron death following spinal root avulsion in adult rats. J Neurotrauma 2003, 20(6):603-612.
  • [17]Wu W: Potential roles of gene expression change in adult rat spinal motoneurons following axonal injury: a comparison among c-jun, off-affinity nerve growth factor receptor (LNGFR), and nitric oxide synthase (NOS). Exp Neurol 1996, 141(2):190-200.
  • [18]Wu W: Expression of nitric-oxide synthase (NOS) in injured CNS neurons as shown by NADPH diaphorase histochemistry. Exp Neurol 1993, 120(2):153-159.
  • [19]Zhou LH, Han S, Xie YY, Wang LL, Yao ZB: Differences in c-jun and nNOS expression levels in motoneurons following different kinds of axonal injury in adult rats. Brain Cell Biol 2008, 36(5–6):213-227.
  • [20]Brandenburger T, Castoldi M, Brendel M, Grievink H, Schlosser L, Werdehausen R, Bauer I, Hermanns H: Expression of spinal cord microRNAs in a rat model of chronic neuropathic pain. Neurosci Lett 2012, 506(2):281-286.
  • [21]Makeyev EV, Zhang J, Carrasco MA, Maniatis T: The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 2007, 27(3):435-448.
  • [22]Bhalala OG, Pan L, Sahni V, McGuire TL, Gruner K, Tourtellotte WG, Kessler JA: microRNA-21 regulates astrocytic response following spinal cord injury. J Neurosci 2012, 32(50):17935-17947.
  • [23]Xie W, Li M, Xu N, Lv Q, Huang N, He J, Zhang Y: MiR-181a regulates inflammation responses in monocytes and macrophages. PLoS One 2013, 8(3):e58639.
  • [24]Liu NK, Wang XF, Lu QB, Xu XM: Altered microRNA expression following traumatic spinal cord injury. Exp Neurol 2009, 219(2):424-429.
  • [25]Yang Y, Xie Y, Chai H, Fan M, Liu S, Liu H, Bruce I, Wu W: Microarray analysis of gene expression patterns in adult spinal motoneurons after different types of axonal injuries. Brain Res 2006, 1075(1):1-12.
  • [26]Hunt JL, Winkelstein BA, Rutkowski MD, Weinstein JN, DeLeo JA: Repeated injury to the lumbar nerve roots produces enhanced mechanical allodynia and persistent spinal neuroinflammation. Spine (Phila Pa 1976) 2001, 26(19):2073-2079.
  • [27]Winkelstein BA, Rutkowski MD, Sweitzer SM, Pahl JL, DeLeo JA: Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment. J Comp Neurol 2001, 439(2):127-139.
  • [28]Winkelstein BA, DeLeo JA: Nerve root injury severity differentially modulates spinal glial activation in a rat lumbar radiculopathy model: considerations for persistent pain. Brain Res 2002, 956(2):294-301.
  • [29]Chew DJ, Carlstedt T, Shortland PJ: A comparative histological analysis of two models of nerve root avulsion injury in the adult rat. Neuropathol Appl Neurobiol 2011, 37(6):613-632.
  • [30]Yu B, Zhou S, Qian T, Wang Y, Ding F, Gu X: Altered microRNA expression following sciatic nerve resection in dorsal root ganglia of rats. Acta Biochim Biophys Sin (Shanghai) 2011, 43(11):909-915.
  • [31]Genda Y, Arai M, Ishikawa M, Tanaka S, Okabe T, Sakamoto A: microRNA changes in the dorsal horn of the spinal cord of rats with chronic constriction injury: A TaqMan(R) Low Density Array study. Int J Mol Med 2013, 31(1):129-137.
  • [32]Donaldson LF: Unilateral arthritis: contralateral effects. Trends Neurosci 1999, 22(11):495-496.
  • [33]Koltzenburg M, Wall PD, McMahon SB: Does the right side know what the left is doing? Trends Neurosci 1999, 22(3):122-127.
  • [34]Llewellyn-Smith IJ, Martin CL, Fenwick NM, Dicarlo SE, Lujan HL, Schreihofer AM: VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord. J Comp Neurol 2007, 503(6):741-767.
  • [35]Alvarez FJ, Villalba RM, Zerda R, Schneider SP: Vesicular glutamate transporters in the spinal cord, with special reference to sensory primary afferent synapses. J Comp Neurol 2004, 472(3):257-280.
  • [36]Wu L, Wu J, Chang HYH, Havton LA: Selective plasticity of primary afferent innervation to the dorsal horn and autonomic nuclei following lumbosacral ventral root avulsion and reimplantation in long term studies. Exp Neurol 2012, 233(2):758-766.
  • [37]Dharap A, Vemuganti R: Ischemic pre-conditioning alters cerebral microRNAs that are upstream to neuroprotective signaling pathways. J Neurochem 2010, 113(6):1685-1691.
  • [38]Genot EM, Arrieumerlou C, Ku G, Burgering BM, Weiss A, Kramer IM: The T-cell receptor regulates Akt (protein kinase B) via a pathway involving Rac1 and phosphatidylinositide 3-kinase. Mol Cell Biol 2000, 20(15):5469-5478.
  • [39]So T, Croft M: Regulation of PI-3-Kinase and Akt Signaling in T Lymphocytes and Other Cells by TNFR Family Molecules. Front Immunol 2013, 4:139.
  • [40]Xu YQ, Long L, Yan JQ, Wei L, Pan MQ, Gao HM, Zhou P, Liu M, Zhu CS, Tang BS, Wang Q: Simvastatin induces neuroprotection in 6-OHDA-lesioned PC12 via the PI3K/AKT/caspase 3 pathway and anti-inflammatory responses. CNS Neurosci Ther 2013, 19(3):170-177.
  • [41]Yuan J, Yankner BA: Apoptosis in the nervous system. Nature 2000, 407(6805):802-809.
  • [42]Herdegen T, Skene P, Bahr M: The c-Jun transcription factor–bipotential mediator of neuronal death, survival and regeneration. Trends Neurosci 1997, 20(5):227-231.
  • [43]Mielke K, Herdegen T: JNK and p38 stresskinases–degenerative effectors of signal-transduction-cascades in the nervous system. Prog Neurobiol 2000, 61(1):45-60.
  • [44]Castagne V, Gautschi M, Lefevre K, Posada A, Clarke PG: Relationships between neuronal death and the cellular redox status. Focus on the developing nervous system. Prog Neurobiol 1999, 59(4):397-423.
  • [45]Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME: Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 1999, 286(5443):1358-1362.
  • [46]Tsujino H, Kondo E, Fukuoka T, Dai Y, Tokunaga A, Miki K, Yonenobu K, Ochi T, Noguchi K: Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury. Mol Cell Neurosci 2000, 15(2):170-182.
  • [47]Pearson AG, Gray CW, Pearson JF, Greenwood JM, During MJ, Dragunow M: ATF3 enhances c-Jun-mediated neurite sprouting. Brain Res Mol Brain Res 2003, 120(1):38-45.
  • [48]Nakagomi S, Suzuki Y, Namikawa K, Kiryu-Seo S, Kiyama H: Expression of the activating transcription factor 3 prevents c-Jun N-terminal kinase-induced neuronal death by promoting heat shock protein 27 expression and Akt activation. J Neurosci 2003, 23(12):5187-5196.
  • [49]Seijffers R, Allchorne AJ, Woolf CJ: The transcription factor ATF-3 promotes neurite outgrowth. Mol Cell Neurosci 2006, 32(1–2):143-154.
  • [50]Schroeter H, Spencer JP, Rice-Evans C, Williams RJ: Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem J 2001, 358(Pt 3):547-557.
  • [51]Fukunaga K, Miyamoto E: A working model of CaM kinase II activity in hippocampal long-term potentiation and memory. Neurosci Res 2000, 38(1):3-17.
  • [52]Han F, Shirasaki Y, Fukunaga K: Microsphere embolism-induced endothelial nitric oxide synthase expression mediates disruption of the blood–brain barrier in rat brain. J Neurochem 2006, 99(1):97-106.
  • [53]Shioda N, Han F, Moriguchi S, Fukunaga K: Constitutively active calcineurin mediates delayed neuronal death through Fas-ligand expression via activation of NFAT and FKHR transcriptional activities in mouse brain ischemia. J Neurochem 2007, 102(5):1506-1517.
  • [54]Zhang GS, Ye WF, Tao RR, Lu YM, Shen GF, Fukunaga K, Huang JY, Ji YL, Han F: Expression profiling of Ca2+/calmodulin-dependent signaling molecules in the rat dorsal and ventral hippocampus after acute lead exposure. Exp Toxicol Pathol 2012, 64(6):619-624.
  • [55]Hajimohammadreza I, Raser KJ, Nath R, Nadimpalli R, Scott M, Wang KK: Neuronal nitric oxide synthase and calmodulin-dependent protein kinase IIalpha undergo neurotoxin-induced proteolysis. J Neurochem 1997, 69(3):1006-1013.
  • [56]Higa GS, de Sousa E, Walter LT, Kinjo ER, Resende RR, Kihara AH: MicroRNAs in Neuronal Communication. Mol Neurobiol 2014, 49(3):1309-1326.
  • [57]Saba R, Storchel PH, Aksoy-Aksel A, Kepura F, Lippi G, Plant TD, Schratt GM: Dopamine-regulated microRNA MiR-181a controls GluA2 surface expression in hippocampal neurons. Mol Cell Biol 2012, 32(3):619-632.
  • [58]Tobon KE, Chang D, Kuzhikandathil EV: MicroRNA 142-3p Mediates Post-Transcriptional Regulation of D1 Dopamine Receptor Expression. Plos One 2012, 7(11):e49288.
  • [59]Yunta M, Nieto-Diaz M, Esteban FJ, Caballero-Lopez M, Navarro-Ruiz R, Reigada D, Pita-Thomas DW, del Aguila A, Munoz-Galdeano T, Maza RM: MicroRNA dysregulation in the spinal cord following traumatic injury. PLoS One 2012, 7(4):e34534.
  • [60]Strickland ER, Hook MA, Balaraman S, Huie JR, Grau JW, Miranda RC: MicroRNA dysregulation following spinal cord contusion: implications for neural plasticity and repair. Neuroscience 2011, 186:146-160.
  • [61]De Biase A, Knoblach SM, Di Giovanni S, Fan C, Molon A, Hoffman EP, Faden AI: Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity. Physiol Genomics 2005, 22(3):368-381.
  • [62]Li S, Zhu J, Zhang W, Chen Y, Zhang K, Popescu LM, Ma X, Lau WB, Rong R, Yu X, Wang B, Li Y, Xiao C, Zhang M, Wang S, Yu L, Chen AF, Yang X, Cai J: Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation 2011, 124(2):175-184.
  • [63]Dweep H, Sticht C, Pandey P, Gretz N: miRWalk–database: prediction of possible miRNA binding sites by "walking" the genes of three genomes. J Biomed Inform 2011, 44(5):839-847.
  • [64]Wu W, Li L: Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion. Neurosci Lett 1993, 153(2):121-124.
  文献评价指标  
  下载次数:62次 浏览次数:7次