Novel Insights into NeuN: from Neuronal Marker to Splicing Regulator

Molecular Neurobiology

Volumn 53, Issue 3, 2016, Pages 1637-1647

  Duan, Wei ^a   Zhang, Yu Ping ^a   Hou, Zhi ^a   Huang, Chen ^b   Zhu, He ^b,c,d   Zhang, Chun Qing ^a   Yin, Qing ^a  

^a THIRD MILITARY MEDICAL UNIVERSITY   (China)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c VANDERBILT UNIVERSITY   (United States)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Mature neurons; NeuN; Neuronal marker; Rbfox3; Splicing regulator

Indexed keywords

BIOLOGICAL MARKER; MESSENGER RNA; NEURON SPECIFIC NUCLEAR PROTEIN; CELL NUCLEUS ANTIGEN; EPITOPE; NERVE PROTEIN; RNA SPLICING FACTOR;

BINDING AFFINITY; CELL MATURATION; CELL MIGRATION; CELLULAR DISTRIBUTION; CHEMICAL STRESS; EXON; GENE; GENE EXPRESSION; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; NERVE CELL; NERVE CELL DIFFERENTIATION; NONHUMAN; PHYSICAL STRESS; PROTEIN BINDING; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; PROTEIN SYNTHESIS; PYRAMIDAL NERVE CELL; RBFOX3 GENE; REVIEW; ALTERNATIVE RNA SPLICING; ANIMAL; AXOTOMY; CELL CULTURE; CELL NUCLEUS; CHEMISTRY; CYTOPLASM; GENE EXPRESSION REGULATION; GENETICS; MENTAL DISEASE; METABOLISM; NEUROLOGIC DISEASE; PHYSIOLOGICAL STRESS; PHYSIOLOGY; VERTEBRATE;

ALTERNATIVE SPLICING; ANIMALS; ANTIGENS, NUCLEAR; AXOTOMY; BIOMARKERS; CELL NUCLEUS; CELLS, CULTURED; CYTOPLASM; EPITOPES; GENE EXPRESSION REGULATION; HUMANS; NERVE TISSUE PROTEINS; NERVOUS SYSTEM DISEASES; NEURODEVELOPMENTAL DISORDERS; NEURONS; RNA SPLICING FACTORS; STRESS, PHYSIOLOGICAL; VERTEBRATES;

EID: 84961136724     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-015-9122-5     Document Type: Review

References (96)

1. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116(1):201–211
2. Huttner HB, Bergmann O, Salehpour M, Racz A, Tatarishvili J, Lindgren E, Csonka T, Csiba L et al (2014) The age and genomic integrity of neurons after cortical stroke in humans. Nat Neurosci 17(6):801–803. doi:10.1038/nn.3706
3. Maxeiner S, Glassmann A, Kao HT, Schilling K (2014) The molecular basis of the specificity and cross-reactivity of the NeuN epitope of the neuron-specific splicing regulator, Rbfox3. Histochem Cell Biol 141(1):43–55. doi:10.1007/s00418-013-1159-9
4. Soylemezoglu F, Onder S, Tezel GG, Berker M (2003) Neuronal nuclear antigen (NeuN): a new tool in the diagnosis of central neurocytoma. Pathol Res Pract 199(7):463–468
5. Sarnat HB, Nochlin D, Born DE (1998) Neuronal nuclear antigen (NeuN): a marker of neuronal maturation in early human fetal nervous system. Brain Dev 20(2):88–94
6. Wolf HK, Buslei R, Schmidt-Kastner R, Schmidt-Kastner PK, Pietsch T, Wiestler OD, Blumcke I (1996) NeuN: a useful neuronal marker for diagnostic histopathology. J Histochem Cytochem 44(10):1167–1171
7. Preusser M, Laggner U, Haberler C, Heinzl H, Budka H, Hainfellner JA (2006) Comparative analysis of NeuN immunoreactivity in primary brain tumours: conclusions for rational use in diagnostic histopathology. Histopathology 48(4):438–444. doi:10.1111/j.1365-2559.2006.02359.x
8. Shen CC, Yang YC, Chiao MT, Cheng WY, Ko JL, Tsuei YS (2010) Characterization of Endogenous Neural Progenitor Cells after Experimental Ischemic Stroke. Curr Neurovasc Res
9. Davoli MA, Fourtounis J, Tam J, Xanthoudakis S, Nicholson D, Robertson GS, Ng GY, Xu D (2002) Immunohistochemical and biochemical assessment of caspase-3 activation and DNA fragmentation following transient focal ischemia in the rat. Neuroscience 115(1):125–136
10. Sugawara T, Lewen A, Noshita N, Gasche Y, Chan PH (2002) Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. J Neurotrauma 19(1):85–98. doi:10.1089/089771502753460268
11. Safford KM, Safford SD, Gimble JM, Shetty AK, Rice HE (2004) Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells. Exp Neurol 187(2):319–328. doi:10.1016/j.expneurol.2004.01.027
12. Long X, Olszewski M, Huang W, Kletzel M (2005) Neural cell differentiation in vitro from adult human bone marrow mesenchymal stem cells. Stem Cells Dev 14(1):65–69. doi:10.1089/scd.2005.14.65
13. Lind D, Franken S, Kappler J, Jankowski J, Schilling K (2005) Characterization of the neuronal marker NeuN as a multiply phosphorylated antigen with discrete subcellular localization. J Neurosci Res 79(3):295–302. doi:10.1002/jnr.20354
14. Kim KK, Adelstein RS, Kawamoto S (2009) Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors. J Biol Chem 284(45):31052–31061. doi:10.1074/jbc.M109.052969
15. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H et al (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539. doi:10.1038/msb.2011.75
16. Damianov A, Black DL (2010) Autoregulation of Fox protein expression to produce dominant negative splicing factors. RNA 16(2):405–416. doi:10.1261/rna.1838210
17. Stuurman N, Meijne AM, van der Pol AJ, de Jong L, van Driel R, van Renswoude J (1990) The nuclear matrix from cells of different origin. Evidence for a common set of matrix proteins. J Biol Chem 265(10):5460–5465
18. Fey EG, Penman S (1988) Nuclear matrix proteins reflect cell type of origin in cultured human cells. Proc Natl Acad Sci U S A 85(1):121–125
19. Dent MA, Segura-Anaya E, Alva-Medina J, Aranda-Anzaldo A (2010) NeuN/Fox-3 is an intrinsic component of the neuronal nuclear matrix. FEBS Lett 584(13):2767–2771. doi:10.1016/j.febslet.2010.04.073
20. Jangi M, Boutz PL, Paul P, Sharp PA (2014) Rbfox2 controls autoregulation in RNA-binding protein networks. Genes Dev 28(6):637–651. doi:10.1101/gad.235770.113
21. Gehman LT, Stoilov P, Maguire J, Damianov A, Lin CH, Shiue L, Ares M Jr, Mody I et al (2011) The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain. Nat Genet 43(7):706–711. doi:10.1038/ng.841
22. Kuroyanagi H (2009) Fox-1 family of RNA-binding proteins. Cell Mol Life Sci: CMLS 66(24):3895–3907. doi:10.1007/s00018-009-0120-5
23. Tang ZZ, Zheng S, Nikolic J, Black DL (2009) Developmental control of CaV1.2 L-type calcium channel splicing by Fox proteins. Mol Cell Biol 29(17):4757–4765. doi:10.1128/MCB. 00608-09
24. Dredge BK, Jensen KB (2011) NeuN/Rbfox3 nuclear and cytoplasmic isoforms differentially regulate alternative splicing and nonsense-mediated decay of Rbfox2. PLoS One 6(6):e21585. doi:10.1371/journal.pone.0021585
25. Xie J (2014) Differential evolution of signal-responsive RNA elements and upstream factors that control alternative splicing. Cell Mol Life Sci: CMLS. doi:10.1007/s00018-014-1688-y
26. Korner M, Miller LJ (2009) Alternative splicing of pre-mRNA in cancer: focus on G protein-coupled peptide hormone receptors. Am J Pathol 175(2):461–472. doi:10.2353/ajpath.2009.081135
27. Kim KK, Kim YC, Adelstein RS, Kawamoto S (2011) Fox-3 and PSF interact to activate neural cell-specific alternative splicing. Nucleic Acids Res 39(8):3064–3078. doi:10.1093/nar/gkq1221
28. McManus CJ, Graveley BR (2011) RNA structure and the mechanisms of alternative splicing. Curr Opin Genet Dev 21(4):373–379. doi:10.1016/j.gde.2011.04.001
29. Kornblihtt AR, Schor IE, Allo M, Dujardin G, Petrillo E, Munoz MJ (2013) Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat Rev Mol Cell Biol 14(3):153–165. doi:10.1038/nrm3525
30. Zheng S, Black DL (2013) Alternative pre-mRNA splicing in neurons: growing up and extending its reach. Trends Genet: TIG 29(8):442–448. doi:10.1016/j.tig.2013.04.003
31. Chih B, Gollan L, Scheiffele P (2006) Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex. Neuron 51(2):171–178. doi:10.1016/j.neuron.2006.06.005
32. Dredge BK, Polydorides AD, Darnell RB (2001) The splice of life: alternative splicing and neurological disease. Nat Rev Neurosci 2(1):43–50. doi:10.1038/35049061
33. Charizanis K, Lee KY, Batra R, Goodwin M, Zhang C, Yuan Y, Shiue L, Cline M et al (2012) Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy. Neuron 75(3):437–450. doi:10.1016/j.neuron.2012.05.029
34. Yeo G, Holste D, Kreiman G, Burge CB (2004) Variation in alternative splicing across human tissues. Genome Biol 5(10):R74. doi:10.1186/gb-2004-5-10-r74
35. Kim KK, Nam J, Mukouyama YS, Kawamoto S (2013) Rbfox3-regulated alternative splicing of Numb promotes neuronal differentiation during development. J Cell Biol 200(4):443–458. doi:10.1083/jcb.201206146
36. Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci U S A 96(10):5768–5773
37. Van Nassauw L, Wu M, De Jonge F, Adriaensen D, Timmermans JP (2005) Cytoplasmic, but not nuclear, expression of the neuronal nuclei (NeuN) antibody is an exclusive feature of Dogiel type II neurons in the guinea-pig gastrointestinal tract. Histochem Cell Biol 124(5):369–377. doi:10.1007/s00418-005-0019-7
38. Weyer A, Schilling K (2003) Developmental and cell type-specific expression of the neuronal marker NeuN in the murine cerebellum. J Neurosci Res 73(3):400–409. doi:10.1002/jnr.10655
39. Morin LP, Hefton S, Studholme KM (2011) Neurons identified by NeuN/Fox-3 immunoreactivity have a novel distribution in the hamster and mouse suprachiasmatic nucleus. Brain Res 1421:44–51. doi:10.1016/j.brainres.2011.09.015
40. Portiansky EL, Barbeito CG, Gimeno EJ, Zuccolilli GO, Goya RG (2006) Loss of NeuN immunoreactivity in rat spinal cord neurons during aging. Exp Neurol 202(2):519–521. doi:10.1016/j.expneurol.2006.07.014
41. Kumar SS, Buckmaster PS (2007) Neuron-specific nuclear antigen NeuN is not detectable in gerbil subtantia nigra pars reticulata. Brain Res 1142:54–60. doi:10.1016/j.brainres.2007.01.027
42. Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290(5497):1775–1779
43. Goetz AK, Scheffler B, Chen HX, Wang S, Suslov O, Xiang H, Brustle O, Roper SN et al (2006) Temporally restricted substrate interactions direct fate and specification of neural precursors derived from embryonic stem cells. Proc Natl Acad Sci U S A 103(29):11063–11068. doi:10.1073/pnas.0510926103
44. Rosser AE, Tyers P, ter Borg M, Dunnett SB, Svendsen CN (1997) Co-expression of MAP-2 and GFAP in cells developing from rat EGF responsive precursor cells. Brain Res Dev Brain Res 98(2):291–295
45. Johnson GV, Jope RS (1992) The role of microtubule-associated protein 2 (MAP-2) in neuronal growth, plasticity, and degeneration. J Neurosci Res 33(4):505–512. doi:10.1002/jnr.490330402
46. Wharton SB, Chan KK, Whittle IR (2002) Microtubule-associated protein 2 (MAP-2) is expressed in low and high grade diffuse astrocytomas. J Clin Neurosci: Off J Neurosurgical Soc Australasia 9(2):165–169. doi:10.1054/jocn.2001.1055
47. Shafit-Zagardo B, Kalcheva N (1998) Making sense of the multiple MAP-2 transcripts and their role in the neuron. Mol Neurobiol 16(2):149–162. doi:10.1007/BF02740642
48. Cronberg T, Rundgren M, Westhall E, Englund E, Siemund R, Rosen I, Widner H, Friberg H (2011) Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology 77(7):623–630. doi:10.1212/WNL.0b013e31822a276d
49. Haimoto H, Takahashi Y, Koshikawa T, Nagura H, Kato K (1985) Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Investig: J Technical Methods Pathol 52(3):257–263
50. Lawson SN, Harper AA, Harper EI, Garson JA, Anderton BH (1984) A monoclonal antibody against neurofilament protein specifically labels a subpopulation of rat sensory neurones. J Comp Neurol 228(2):263–272. doi:10.1002/cne.902280211
51. Lawson SN, Waddell PJ (1991) Soma neurofilament immunoreactivity is related to cell size and fibre conduction velocity in rat primary sensory neurons. J Physiol 435:41–63
52. Voelker CC, Garin N, Taylor JS, Gahwiler BH, Hornung JP, Molnar Z (2004) Selective neurofilament (SMI-32, FNP-7 and N200) expression in subpopulations of layer V pyramidal neurons in vivo and in vitro. Cereb Cortex 14(11):1276–1286. doi:10.1093/cercor/bhh089
53. Gould VE, Lee I, Wiedenmann B, Moll R, Chejfec G, Franke WW (1986) Synaptophysin: a novel marker for neurons, certain neuroendocrine cells, and their neoplasms. Hum Pathol 17(10):979–983
54. Kepes JJ, Collins J (1999) Choroid plexus epithelium (normal and neoplastic) expresses synaptophysin. A potentially useful aid in differentiating carcinoma of the choroid plexus from metastatic papillary carcinomas. J Neuropathol Exp Neurol 58(4):398–401
55. Sarnat HB, Flores-Sarnat L, Trevenen CL (2010) Synaptophysin immunoreactivity in the human hippocampus and neocortex from 6 to 41 weeks of gestation. J Neuropathol Exp Neurol 69(3):234–245. doi:10.1097/NEN.0b013e3181d0151f
56. Lee VM, Otvos L Jr, Carden MJ, Hollosi M, Dietzschold B, Lazzarini RA (1988) Identification of the major multiphosphorylation site in mammalian neurofilaments. Proc Natl Acad Sci U S A 85(6):1998–2002
57. Ouda L, Druga R, Syka J (2012) Distribution of SMI-32-immunoreactive neurons in the central auditory system of the rat. Brain Struct Funct 217(1):19–36. doi:10.1007/s00429-011-0329-6
58. Beyer K, Ariza A (2013) alpha-Synuclein posttranslational modification and alternative splicing as a trigger for neurodegeneration. Mol Neurobiol 47(2):509–524. doi:10.1007/s12035-012-8330-5
59. Cooper TA, Wan L, Dreyfuss G (2009) RNA and disease. Cell 136(4):777–793. doi:10.1016/j.cell.2009.02.011
60. Elia J, Glessner JT, Wang K, Takahashi N, Shtir CJ, Hadley D, Sleiman PM, Zhang H et al (2012) Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. Nat Genet 44(1):78–84. doi:10.1038/ng.1013
61. Lee JA, Tang ZZ, Black DL (2009) An inducible change in Fox-1/A2BP1 splicing modulates the alternative splicing of downstream neuronal target exons. Genes Dev 23(19):2284–2293. doi:10.1101/gad.1837009
62. Bill BR, Lowe JK, Dybuncio CT, Fogel BL (2013) Orchestration of neurodevelopmental programs by RBFOX1: implications for autism spectrum disorder. Int Rev Neurobiol 113:251–267. doi:10.1016/B978-0-12-418700-9.00008-3
63. O’Brien JE, Drews VL, Jones JM, Dugas JC, Barres BA, Meisler MH (2012) Rbfox proteins regulate alternative splicing of neuronal sodium channel SCN8A. Mol Cell Neurosci 49(2):120–126. doi:10.1016/j.mcn.2011.10.005
64. Fogel BL, Wexler E, Wahnich A, Friedrich T, Vijayendran C, Gao F, Parikshak N, Konopka G et al (2012) RBFOX1 regulates both splicing and transcriptional networks in human neuronal development. Hum Mol Genet 21(19):4171–4186. doi:10.1093/hmg/dds240
65. Lal D, Reinthaler EM, Altmuller J, Toliat MR, Thiele H, Nurnberg P, Lerche H, Hahn A et al (2013) RBFOX1 and RBFOX3 mutations in rolandic epilepsy. PLoS One 8(9):e73323. doi:10.1371/journal.pone.0073323
66. Vandeweyer G, Kooy RF (2009) Balanced translocations in mental retardation. Hum Genet 126(1):133–147. doi:10.1007/s00439-009-0661-6
67. Utami KH, Hillmer AM, Aksoy I, Chew EG, Teo AS, Zhang Z, Lee CW, Chen PJ et al (2014) Detection of chromosomal breakpoints in patients with developmental delay and speech disorders. PLoS One 9(6):e90852. doi:10.1371/journal.pone.0090852
68. Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H et al (2011) A copy number variation morbidity map of developmental delay. Nat Genet 43(9):838–846. doi:10.1038/ng.909
69. Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX, Zhang Z (2000) Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 20(9):1311–1319. doi:10.1097/00004647-200009000-00006
70. Toda H, Takahashi J, Iwakami N, Kimura T, Hoki S, Mozumi-Kitamura K, Ono S, Hashimoto N (2001) Grafting neural stem cells improved the impaired spatial recognition in ischemic rats. Neurosci Lett 316(1):9–12
71. Unal-Cevik I, Kilinc M, Gursoy-Ozdemir Y, Gurer G, Dalkara T (2004) Loss of NeuN immunoreactivity after cerebral ischemia does not indicate neuronal cell loss: a cautionary note. Brain Res 1015(1–2):169–174. doi:10.1016/j.brainres.2004.04.032
72. Hartmann A, Hunot S, Michel PP, Muriel MP, Vyas S, Faucheux BA, Mouatt-Prigent A, Turmel H et al (2000) Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson’s disease. Proc Natl Acad Sci U S A 97(6):2875–2880. doi:10.1073/pnas.040556597
73. Arenas E, Trupp M, Akerud P, Ibanez CF (1995) GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo. Neuron 15(6):1465–1473
74. Patil DA, Patil VA, Bari SB, Surana SJ, Patil PO (2014) Animal Models for Parkinson’s Disease. CNS & neurological disorders drug targets
75. Mount MP, Lira A, Grimes D, Smith PD, Faucher S, Slack R, Anisman H, Hayley S et al (2007) Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons. J Neurosci 27(12):3328–3337. doi:10.1523/JNEUROSCI. 5321-06.2007
76. Lee Y, Dawson VL, Dawson TM (2012) Animal models of Parkinson’s disease: vertebrate genetics. Cold Spring Harbor perspectives in medicine 2 (10). doi:10.1101/cshperspect.a009324
77. Baquet ZC, Bickford PC, Jones KR (2005) Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 25(26):6251–6259. doi:10.1523/JNEUROSCI. 4601-04.2005
78. Novikova L, Garris BL, Garris DR, Lau YS (2006) Early signs of neuronal apoptosis in the substantia nigra pars compacta of the progressive neurodegenerative mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model of Parkinson’s disease. Neuroscience 140(1):67–76. doi:10.1016/j.neuroscience.2006.02.007
79. Zhu C, Vourc’h P, Fernagut PO, Fleming SM, Lacan S, Dicarlo CD, Seaman RL, Chesselet MF (2004) Variable effects of chronic subcutaneous administration of rotenone on striatal histology. J Comp Neurol 478(4):418–426. doi:10.1002/cne.20305
80. Cannon JR, Greenamyre JT (2009) NeuN is not a reliable marker of dopamine neurons in rat substantia nigra. Neurosci Lett 464(1):14–17. doi:10.1016/j.neulet.2009.08.023
81. Lavezzi AM, Corna MF, Matturri L (2013) Neuronal nuclear antigen (NeuN): a useful marker of neuronal immaturity in sudden unexplained perinatal death. J Neurol Sci 329(1–2):45–50. doi:10.1016/j.jns.2013.03.012
82. Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA et al (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirology 17(1):3–16. doi:10.1007/s13365-010-0006-1
83. Foley JM, Wright MJ, Gooding AL, Ettenhofer M, Kim M, Choi M, Castellon SA, Sadek J et al (2011) Operationalization of the updated diagnostic algorithm for classifying HIV-related cognitive impairment and dementia. Int Psychogeriatr / IPA 23(5):835–843. doi:10.1017/S1041610210002085
84. Gannon P, Khan MZ, Kolson DL (2011) Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 24(3):275–283. doi:10.1097/WCO.0b013e32834695fb
85. Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8(1):33–44. doi:10.1038/nrn2040
86. Lucas CH, Calvez M, Babu R, Brown A (2014) Altered subcellular localization of the NeuN/Rbfox3 RNA splicing factor in HIV-associated neurocognitive disorders (HAND). Neurosci Lett 558:97–102. doi:10.1016/j.neulet.2013.10.037
87. Orlova KA, Crino PB (2010) The tuberous sclerosis complex. Ann N Y Acad Sci 1184:87–105. doi:10.1111/j.1749-6632.2009.05117.x
88. Zhang CQ, Shu HF, Yin Q, An N, Xu SL, Yin JB, Song YC, Liu SY et al (2012) Expression and cellular distribution of vascular endothelial growth factor-C system in cortical tubers of the tuberous sclerosis complex. Brain Pathol 22(2):205–218. doi:10.1111/j.1750-3639.2011.00519.x
89. Sugimoto T, Xiao C, Ichikawa H (1998) Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism. Brain Res 807(1–2):147–154
90. McPhail LT, McBride CB, McGraw J, Steeves JD, Tetzlaff W (2004) Axotomy abolishes NeuN expression in facial but not rubrospinal neurons. Exp Neurol 185(1):182–190
91. Benn SC, Woolf CJ (2004) Adult neuron survival strategies–slamming on the brakes. Nat Rev Neurosci 5(9):686–700. doi:10.1038/nrn1477
92. Collombet JM, Masqueliez C, Four E, Burckhart MF, Bernabe D, Baubichon D, Lallement G (2006) Early reduction of NeuN antigenicity induced by soman poisoning in mice can be used to predict delayed neuronal degeneration in the hippocampus. Neurosci Lett 398(3):337–342. doi:10.1016/j.neulet.2006.01.029
93. Wu KL, Li YQ, Tabassum A, Lu WY, Aubert I, Wong CS (2010) Loss of Neuronal Protein Expression in Mouse Hippocampus After Irradiation. J Neuropathol Exp Neurol 69(3):272–280. doi:10.1097/NEN.0b013e3181d1afe4
94. Darlington PJ, Goldman JS, Cui QL, Antel JP, Kennedy TE (2008) Widespread immunoreactivity for neuronal nuclei in cultured human and rodent astrocytes. J Neurochem 104(5):1201–1209. doi:10.1111/j.1471-4159.2007.05043.x
95. Polydorides AD, Okano HJ, Yang YY, Stefani G, Darnell RB (2000) A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. Proc Natl Acad Sci U S A 97(12):6350–6355. doi:10.1073/pnas.110128397
96. Pascale A, Gusev PA, Amadio M, Dottorini T, Govoni S, Alkon DL, Quattrone A (2004) Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory. Proc Natl Acad Sci U S A 101(5):1217–1222. doi:10.1073/pnas.0307674100