期刊论文详细信息
Journal of Neuroinflammation
Serum response factor modulates neuron survival during peripheral axon injury
Bernd Knöll1  Daniela Sinske1  Sina Stern2 
[1] Current addresses: Institute for Physiological Chemistry, Ulm University, Ulm, 89081, Germany;Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, 53175, Germany
关键词: Microglia;    Axon;    SRF;    Regeneration;    Motorneuron;    Immune cell;    Facial nerve;   
Others  :  1212654
DOI  :  10.1186/1742-2094-9-78
 received in 2011-08-15, accepted in 2012-04-26,  发布年份 2012
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【 摘 要 】

Background

The transcription factor SRF (serum response factor) mediates neuronal survival in vitro. However, data available so far suggest that SRF is largely dispensable for neuron survival during physiological brain function.

Findings

Here, we demonstrate that upon neuronal injury, that is facial nerve transection, constitutively-active SRF-VP16 enhances motorneuron survival. SRF-VP16 suppressed active caspase 3 abundance in vitro and enhanced neuron survival upon camptothecin induced apoptosis. Following nerve fiber injury in vitro, SRF-VP16 improved survival of neurons and re-growth of severed neurites. Further, SRF-VP16 enhanced immune responses (that is microglia and T cell activation) associated with neuronal injury in vivo. Genome-wide transcriptomics identified target genes associated with axonal injury and modulated by SRF-VP16.

Conclusion

In sum, this is a first report describing a neuronal injury-related survival function for SRF.

【 授权许可】

   
2012 Stern et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Knoll B, Nordheim A: Functional versatility of transcription factors in the nervous system: the SRF paradigm. Trends Neurosci 2009, 32:432-442.
  • [2]Sun K, Battle MA, Misra RP, Duncan SA: Hepatocyte expression of serum response factor is essential for liver function, hepatocyte proliferation and survival, and postnatal body growth in mice. Hepatology 2009, 49:1645-1654.
  • [3]Fleige A, Alberti S, Grobe L, Frischmann U, Geffers R, Muller W, Nordheim A, Schippers A: Serum response factor contributes selectively to lymphocyte development. J Biol Chem 2007, 282:24320-24328.
  • [4]Niu Z, Yu W, Zhang SX, Barron M, Belaguli NS, Schneider MD, Parmacek M, Nordheim A, Schwartz RJ: Conditional mutagenesis of the murine serum response factor gene blocks cardiogenesis and the transcription of downstream gene targets. J Biol Chem 2005, 280:32531-32538.
  • [5]Schratt G, Philippar U, Hockemeyer D, Schwarz H, Alberti S, Nordheim A: SRF regulates Bcl-2 expression and promotes cell survival during murine embryonic development. EMBO J 2004, 23:1834-1844.
  • [6]Chang SH, Poser S, Xia Z: A novel role for serum response factor in neuronal survival. J Neurosci 2004, 24:2277-2285.
  • [7]Kim KH, Min YK, Baik JH, Lau LF, Chaqour B, Chung KC: Expression of angiogenic factor Cyr61 during neuronal cell death via the activation of c-Jun N-terminal kinase and serum response factor. J Biol Chem 2003, 278:13847-13854.
  • [8]Chen SC, Curran T, Morgan JI: Apoptosis in the nervous system: new revelations. J Clin Pathol 1995, 48:7-12.
  • [9]Olson EN, Nordheim A: Linking actin dynamics and gene transcription to drive cellular motile functions. Nat Rev Mol Cell Biol 2010, 11:353-365.
  • [10]Barrett LE, Van Bockstaele EJ, Sul JY, Takano H, Haydon PG, Eberwine JH: Elk-1 associates with the mitochondrial permeability transition pore complex in neurons. Proc Natl Acad Sci U S A 2006, 103:5155-5160.
  • [11]Besnard A, Galan-Rodriguez B, Vanhoutte P, Caboche J: Elk-1 a transcription factor with multiple facets in the brain. Front Neurosci 2011, 5:35.
  • [12]Cao XL, Hu XM, Hu JQ, Zheng WX: Myocardin-related transcription factor-A promoting neuronal survival against apoptosis induced by hypoxia/ischemia. Brain Res 2011, 1385:263-274.
  • [13]Demir O, Aysit N, Onder Z, Turkel N, Ozturk G, Sharrocks AD, Kurnaz IA: ETS-domain transcription factor Elk-1 mediates neuronal survival: SMN as a potential target. Biochim Biophys Acta 2011, 1812:652-662.
  • [14]Vickers ER, Kasza A, Kurnaz IA, Seifert A, Zeef LA, O'Donnell A, Hayes A, Sharrocks AD: Ternary complex factor-serum response factor complex-regulated gene activity is required for cellular proliferation and inhibition of apoptotic cell death. Mol Cell Biol 2004, 24:10340-10351.
  • [15]Alberti S, Krause SM, Kretz O, Philippar U, Lemberger T, Casanova E, Wiebel FF, Schwarz H, Frotscher M, Schutz G, Nordheim A: Neuronal migration in the murine rostral migratory stream requires serum response factor. Proc Natl Acad Sci U S A 2005, 102:6148-6153.
  • [16]Ramanan N, Shen Y, Sarsfield S, Lemberger T, Schutz G, Linden DJ, Ginty DD: SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci 2005, 8:759-767.
  • [17]Wickramasinghe SR, Alvania RS, Ramanan N, Wood JN, Mandai K, Ginty DD: Serum response factor mediates NGF-dependent target innervation by Embryonic DRG sensory neurons. Neuron 2008, 58:532-545.
  • [18]Moran LB, Graeber MB: The facial nerve axotomy model. Brain Res Brain Res Rev 2004, 44:154-178.
  • [19]Raivich G, Bohatschek M, Da Costa C, Iwata O, Galiano M, Hristova M, Nateri AS, Makwana M, Riera-Sans L, Wolfer DP, Lipp HP, Aguzzi A, Wagner EF, Behrens A: The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron 2004, 43:57-67.
  • [20]Knoll B, Kretz O, Fiedler C, Alberti S, Schutz G, Frotscher M, Nordheim A: Serum response factor controls neuronal circuit assembly in the hippocampus. Nat Neurosci 2006, 9:195-204.
  • [21]Stern S, Debre E, Stritt C, Berger J, Posern G, Knoll B: A nuclear actin function regulates neuronal motility by serum response factor-dependent gene transcription. J Neurosci 2009, 29:4512-4518.
  • [22]Neumann H, Kotter MR, Franklin RJ: Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 2009, 132:288-295.
  • [23]Shokouhi BN, Wong BZ, Siddiqui S, Lieberman AR, Campbell G, Tohyama K, Anderson PN: Microglial responses around intrinsic CNS neurons are correlated with axonal regeneration. BMC Neurosci 2010, 11:13. BioMed Central Full Text
  • [24]Raivich G, Jones LL, Kloss CU, Werner A, Neumann H, Kreutzberg GW: Immune surveillance in the injured nervous system: T-lymphocytes invade the axotomized mouse facial motor nucleus and aggregate around sites of neuronal degeneration. J Neurosci 1998, 18:5804-5816.
  • [25]Zujovic V, Luo D, Baker HV, Lopez MC, Miller KR, Streit WJ, Harrison JK: The facial motor nucleus transcriptional program in response to peripheral nerve injury identifies Hn1 as a regeneration-associated gene. J Neurosci Res 2005, 82:581-591.
  • [26]Barrett LE, Sul JY, Takano H, Van Bockstaele EJ, Haydon PG, Eberwine JH: Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Nat Methods 2006, 3:455-460.
  • [27]Thiel G, Cibelli G: Regulation of life and death by the zinc finger transcription factor Egr-1. J Cell Physiol 2002, 193:287-292.
  • [28]Paul AP, Pohl-Guimaraes F, Krahe TE, Filgueiras CC, Lantz CL, Colello RJ, Wang W, Medina AE: Overexpression of serum response factor restores ocular dominance plasticity in a model of fetal alcohol spectrum disorders. J Neurosci 2010, 30:2513-2520.
  • [29]Stritt C, Stern S, Harting K, Manke T, Sinske D, Schwarz H, Vingron M, Nordheim A, Knoll B: Paracrine control of oligodendrocyte differentiation by SRF-directed neuronal gene expression. Nat Neurosci 2009, 12:418-427.
  • [30]Welser-Alves JV, Crocker SJ, Milner R: A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP) expression in glial cells in response to neuroinflammatory stimuli. J Neuroinflammation 2011, 8:61. BioMed Central Full Text
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