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Neuronal network remodeling and Wnt pathway dysregulation in the intra-hippocampal kainate mouse model of temporal lobe epilepsy


Autoři: Kunal Gupta aff001;  Eric Schnell aff002
Působiště autorů: Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon, United States of America aff001;  Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, Oregon, United States of America aff002;  VA Portland Health Care System, Portland, Oregon, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0215789

Souhrn

Mouse models of mesial temporal lobe epilepsy recapitulate aspects of human epilepsy, which is characterized by neuronal network remodeling in the hippocampal dentate gyrus. Observational studies suggest that this remodeling is associated with altered Wnt pathway signaling, although this has not been experimentally examined. We used the well-characterized mouse intrahippocampal kainate model of temporal lobe epilepsy to examine associations between hippocampal neurogenesis and altered Wnt signaling after seizure induction. Tissue was analyzed using immunohistochemistry and confocal microscopy, and gene expression analysis was performed by RT-qPCR on RNA extracted from anatomically micro-dissected dentate gyri. Seizures increased neurogenesis and dendritic arborization of newborn hippocampal dentate granule cells in peri-ictal regions, and decreased neurogenesis in the ictal zone, 2-weeks after kainate injection. Interestingly, administration of the novel canonical Wnt pathway inhibitor XAV939 daily for 2-weeks after kainate injection further increased dendritic arborization in peri-ictal regions after seizure, without an effect on baseline neurogenesis in control animals. Transcriptome analysis of dentate gyri demonstrated significant canonical Wnt gene dysregulation in kainate-injected mice across all regions for Wnt3, 5a and 9a. Intriguingly, certain Wnt genes demonstrated differential patterns of dysregulation between the ictal and peri-ictal zones, most notably Wnt5B, 7B and DKK-1. Together, these results demonstrate regional variation in Wnt pathway dysregulation early after seizure induction, and surprisingly, suggest that some Wnt-mediated effects might actually temper aberrant neurogenesis after seizures. The Wnt pathway may therefore provide suitable targets for novel therapies that prevent network remodeling and the development of epileptic foci in high-risk patients.

Klíčová slova:

Wnt signaling cascade – Hippocampus – Neuronal dendrites – Neurogenesis – Granule cells – Dentate gyrus – Hippocampal neurogenesis – Epilepsy


Zdroje

1. Frey LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia. 2003;44(s10):11–7. doi: 10.1046/j.1528-1157.44.s10.4.x 14511389

2. Ramantani G, Holthausen H. Epilepsy after cerebral infection: review of the literature and the potential for surgery. Epileptic disorders: international epilepsy journal with videotape. 2017;19(2):117–36. doi: 10.1684/epd.2017.0916 28637636

3. Myint PK, Staufenberg EF, Sabanathan K. Post-stroke seizure and post-stroke epilepsy. Postgraduate medical journal. 2006;82(971):568–72. doi: 10.1136/pgmj.2005.041426 16954451

4. French JA. Febrile seizures: possible outcomes. Neurology. 2012;79(9):e80–2. Epub 2012/08/29. doi: 10.1212/WNL.0b013e31826aa902 22927686.

5. French JA. Refractory epilepsy: clinical overview. Epilepsia. 2007;48 Suppl 1:3–7. doi: 10.1111/j.1528-1167.2007.00992.x 17316406

6. Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia. 2001;42(4):515–24. doi: 10.1046/j.1528-1157.2001.28900.x 11440347.

7. Loscher W. Animal Models of Seizures and Epilepsy: Past, Present, and Future Role for the Discovery of Antiseizure Drugs. Neurochemical research. 2017;42(7):1873–88. Epub 2017/03/16. doi: 10.1007/s11064-017-2222-z 28290134.

8. Grone BP, Baraban SC. Animal models in epilepsy research: legacies and new directions. Nature neuroscience. 2015;18(3):339–43. Epub 2015/02/25. doi: 10.1038/nn.3934 25710835.

9. Levesque M, Avoli M. The kainic acid model of temporal lobe epilepsy. Neurosci Biobehav Rev. 2013;37(10 Pt 2):2887–99. Epub 2013/11/05. doi: 10.1016/j.neubiorev.2013.10.011 24184743; PubMed Central PMCID: PMC4878897.

10. Nadler JV, Spencer DD. What is a seizure focus? Advances in experimental medicine and biology. 2014;813:55–62. doi: 10.1007/978-94-017-8914-1_4 25012366

11. Sheybani L, Birot G, Contestabile A, Seeck M, Kiss JZ, Schaller K, et al. Electrophysiological Evidence for the Development of a Self-Sustained Large-Scale Epileptic Network in the Kainate Mouse Model of Temporal Lobe Epilepsy. J Neurosci. 2018;38(15):3776–91. Epub 2018/03/21. doi: 10.1523/JNEUROSCI.2193-17.2018 29555850.

12. Wendling F, Chauvel P, Biraben A, Bartolomei F. From intracerebral EEG signals to brain connectivity: identification of epileptogenic networks in partial epilepsy. Front Syst Neurosci. 2010;4:154. Epub 2010/12/15. doi: 10.3389/fnsys.2010.00154 21152345; PubMed Central PMCID: PMC2998039.

13. Häussler U, Bielefeld L, Froriep UP, Wolfart J, Haas CA. Septotemporal position in the hippocampal formation determines epileptic and neurogenic activity in temporal lobe epilepsy. Cerebral cortex (New York, NY: 1991). 2012;22(1):26–36. doi: 10.1093/cercor/bhr054 21572089

14. Kralic JE, Ledergerber DA, Fritschy J-MM. Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures. The European journal of neuroscience. 2005;22(8):1916–27. doi: 10.1111/j.1460-9568.2005.04386.x 16262631

15. Oliva CA, Vargas JY, Inestrosa NC. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies. Frontiers in cellular neuroscience. 2013;7:224. Epub 2013/12/19. doi: 10.3389/fncel.2013.00224 24348327; PubMed Central PMCID: PMC3847898.

16. Gao X, Arlotta P, Macklis JD, Chen J. Conditional knock-out of beta-catenin in postnatal-born dentate gyrus granule neurons results in dendritic malformation. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2007;27(52):14317–25. doi: 10.1523/JNEUROSCI.3206-07.2007 18160639

17. Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature. 2005;437(7063):1370–5. Epub 2005/10/28. doi: 10.1038/nature04108 16251967.

18. Kron MM, Zhang H, Parent JM. The developmental stage of dentate granule cells dictates their contribution to seizure-induced plasticity. J Neurosci. 2010;30(6):2051–9. doi: 10.1523/JNEUROSCI.5655-09.2010 20147533.

19. Parent JM, Murphy GG. Mechanisms and functional significance of aberrant seizure-induced hippocampal neurogenesis. Epilepsia. 2008;49 Suppl 5:19–25. doi: 10.1111/j.1528-1167.2008.01634.x 18522597.

20. Cho KO, Lybrand ZR, Ito N, Brulet R, Tafacory F, Zhang L, et al. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nature communications. 2015;6:6606. doi: 10.1038/ncomms7606 25808087; PubMed Central PMCID: PMC4375780.

21. Theilhaber J, Rakhade SN, Sudhalter J, Kothari N, Klein P, Pollard J, et al. Gene expression profiling of a hypoxic seizure model of epilepsy suggests a role for mTOR and Wnt signaling in epileptogenesis. PloS one. 2013;8(9):e74428. Epub 2013/10/03. doi: 10.1371/journal.pone.0074428 24086344; PubMed Central PMCID: PMC3785482.

22. Hodges SL, Lugo JN. Wnt/beta-catenin signaling as a potential target for novel epilepsy therapies. Epilepsy research. 2018;146:9–16. Epub 2018/07/28. doi: 10.1016/j.eplepsyres.2018.07.002 30053675.

23. Qu Z, Su F, Qi X, Sun J, Wang H, Qiao Z, et al. Wnt/beta-catenin signalling pathway mediated aberrant hippocampal neurogenesis in kainic acid-induced epilepsy. Cell Biochem Funct. 2017;35(7):472–6. Epub 2017/10/21. doi: 10.1002/cbf.3306 29052243.

24. Overstreet LS, Hentges ST, Bumaschny VF, de Souza FS, Smart JL, Santangelo AM, et al. A transgenic marker for newly born granule cells in dentate gyrus. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2004;24(13):3251–9. doi: 10.1523/JNEUROSCI.5173-03.2004 15056704

25. Huang S-MAM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009;461(7264):614–20. doi: 10.1038/nature08356 19759537

26. Twele F, Tollner K, Brandt C, Loscher W. Significant effects of sex, strain, and anesthesia in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy. Epilepsy Behav. 2016;55:47–56. Epub 2016/01/07. doi: 10.1016/j.yebeh.2015.11.027 26736063.

27. Krook-Magnuson E, Armstrong C, Bui A, Lew S, Oijala M, Soltesz I. In vivo evaluation of the dentate gate theory in epilepsy. The Journal of physiology. 2015;593(10):2379–88. Epub 2015/03/11. doi: 10.1113/JP270056 25752305; PubMed Central PMCID: PMC4457198.

28. Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalography and clinical neurophysiology. 1972;32(3):281–94. doi: 10.1016/0013-4694(72)90177-0 4110397.

29. Bouilleret V, Ridoux V, Depaulis A, Marescaux C, Nehlig A, Le Gal La Salle G. Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience. 1999;89(3):717–29. Epub 1999/04/13. doi: 10.1016/s0306-4522(98)00401-1 10199607.

30. Riban V, Bouilleret V, Pham-Le BT, Fritschy JM, Marescaux C, Depaulis A. Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience. 2002;112(1):101–11. Epub 2002/06/05. doi: 10.1016/s0306-4522(02)00064-7 12044475.

31. Twele F, Schidlitzki A, Tollner K, Loscher W. The intrahippocampal kainate mouse model of mesial temporal lobe epilepsy: Lack of electrographic seizure-like events in sham controls. Epilepsia Open. 2017;2(2):180–7. Epub 2018/03/29. doi: 10.1002/epi4.12044 29588947; PubMed Central PMCID: PMC5719860.

32. Gordon RY, Shubina LV, Kapralova MV, Pershina EB, Khutzian SS, Arhipov VI. [Peculiarities of neurodegeneration in hippocampus fields after kainic acid action in rats]. Tsitologiia. 2014;56(12):919–25. Epub 2014/01/01. 25929133.

33. Heinrich C, Nitta N, Flubacher A, Muller M, Fahrner A, Kirsch M, et al. Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus. J Neurosci. 2006;26(17):4701–13. Epub 2006/04/28. doi: 10.1523/JNEUROSCI.5516-05.2006 16641251.

34. Kiasalari Z, Roghani M, Khalili M, Rahmati B, Baluchnejadmojarad T. Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy. Pharm Biol. 2013;51(12):1572–8. Epub 2013/09/06. doi: 10.3109/13880209.2013.803128 24004105.

35. Lee JM, Hong J, Moon GJ, Jung UJ, Won SY, Kim SR. Morin Prevents Granule Cell Dispersion and Neurotoxicity via Suppression of mTORC1 in a Kainic Acid-induced Seizure Model. Exp Neurobiol. 2018;27(3):226–37. Epub 2018/07/20. doi: 10.5607/en.2018.27.3.226 30022874; PubMed Central PMCID: PMC6050420.

36. Overstreet-Wadiche LS, Bromberg DA, Bensen AL, Westbrook GL. Seizures accelerate functional integration of adult-generated granule cells. J Neurosci. 2006;26(15):4095–103. doi: 10.1523/JNEUROSCI.5508-05.2006 16611826.

37. Chen L, Guo P, Zhang H, Li W, Gao C, Huang Z, et al. Benzene-induced mouse hematotoxicity is regulated by a protein phosphatase 2A complex that stimulates transcription of cytochrome P4502E1. J Biol Chem. 2019;294(7):2486–99. Epub 2018/12/21. doi: 10.1074/jbc.RA118.006319 30567741; PubMed Central PMCID: PMC6378973.

38. Chen X, Shi C, Meng X, Zhang K, Li X, Wang C, et al. Inhibition of Wnt/beta-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-beta1 and FGF-2. Exp Mol Pathol. 2016;101(1):22–30. Epub 2016/04/27. doi: 10.1016/j.yexmp.2016.04.003 27112840; PubMed Central PMCID: PMC5168757.

39. Wang C, Zhu H, Sun Z, Xiang Z, Ge Y, Ni C, et al. Inhibition of Wnt/beta-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury. Am J Physiol Cell Physiol. 2014;307(3):C234–44. Epub 2014/06/06. doi: 10.1152/ajpcell.00366.2013 24898581.

40. Schouten M, Bielefeld P, Fratantoni SA, Hubens CJ, Piersma SR, Pham TV, et al. Multi-omics profile of the mouse dentate gyrus after kainic acid-induced status epilepticus. Sci Data. 2016;3:160068. Epub 2016/08/17. doi: 10.1038/sdata.2016.68 27529540; PubMed Central PMCID: PMC4986542.

41. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8. Epub 2002/02/16. doi: 10.1006/meth.2001.1262 11846609.

42. Marx M, Haas CA, Haussler U. Differential vulnerability of interneurons in the epileptic hippocampus. Frontiers in cellular neuroscience. 2013;7:167. Epub 2013/10/08. doi: 10.3389/fncel.2013.00167 24098270; PubMed Central PMCID: PMC3787650.

43. Nitta N, Heinrich C, Hirai H, Suzuki F. Granule cell dispersion develops without neurogenesis and does not fully depend on astroglial cell generation in a mouse model of temporal lobe epilepsy. Epilepsia. 2008;49(10):1711–22. Epub 2008/04/10. doi: 10.1111/j.1528-1167.2008.01595.x 18397295.

44. Hendricks WD, Chen Y, Bensen AL, Westbrook GL, Schnell E. Short-Term Depression of Sprouted Mossy Fiber Synapses from Adult-Born Granule Cells. J Neurosci. 2017;37(23):5722–35. doi: 10.1523/JNEUROSCI.0761-17.2017 28495975; PubMed Central PMCID: PMC5469308.

45. Scharfman HE, Sollas AL, Berger RE, Goodman JH. Electrophysiological evidence of monosynaptic excitatory transmission between granule cells after seizure-induced mossy fiber sprouting. Journal of neurophysiology. 2003;90(4):2536–47. doi: 10.1152/jn.00251.2003 14534276.

46. Bouilleret V, Schwaller B, Schurmans S, Celio MR, Fritschy JM. Neurodegenerative and morphogenic changes in a mouse model of temporal lobe epilepsy do not depend on the expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin. Neuroscience. 2000;97(1):47–58. Epub 2000/04/20. doi: 10.1016/s0306-4522(00)00017-8 10771338.

47. Jessberger S, Romer B, Babu H, Kempermann G. Seizures induce proliferation and dispersion of doublecortin-positive hippocampal progenitor cells. Experimental neurology. 2005;196(2):342–51. doi: 10.1016/j.expneurol.2005.08.010 16168988.

48. Barone P, Morelli M, Cicarelli G, Cozzolino A, DeJoanna G, Campanella G, et al. Expression of c-fos protein in the experimental epilepsy induced by pilocarpine. Synapse (New York, NY. 1993;14(1):1–9. doi: 10.1002/syn.890140102 8511714.

49. West AE, Greenberg ME. Neuronal activity-regulated gene transcription in synapse development and cognitive function. Cold Spring Harb Perspect Biol. 2011;3(6). Epub 2011/05/11. doi: 10.1101/cshperspect.a005744 21555405; PubMed Central PMCID: PMC3098681.

50. Harvey BD, Sloviter RS. Hippocampal granule cell activity and c-Fos expression during spontaneous seizures in awake, chronically epileptic, pilocarpine-treated rats: implications for hippocampal epileptogenesis. The Journal of comparative neurology. 2005;488(4):442–63. Epub 2005/06/24. doi: 10.1002/cne.20594 15973680.

51. Peng Z, Houser CR. Temporal patterns of fos expression in the dentate gyrus after spontaneous seizures in a mouse model of temporal lobe epilepsy. J Neurosci. 2005;25(31):7210–20. Epub 2005/08/05. doi: 10.1523/JNEUROSCI.0838-05.2005 16079403

52. Tauck DL, Nadler JV. Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. J Neurosci. 1985;5(4):1016–22. 3981241

53. Dingledine R, Coulter DA, Fritsch B, Gorter JA, Lelutiu N, McNamara J, et al. Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models. Scientific data. 2017;4:170061. doi: 10.1038/sdata.2017.61 28485718

54. Ribak CE, Tran PH, Spigelman I, Okazaki MM, Nadler JV. Status epilepticus-induced hilar basal dendrites on rodent granule cells contribute to recurrent excitatory circuitry. The Journal of comparative neurology. 2000;428(2):240–53. Epub 2000/11/07. doi: 10.1002/1096-9861(20001211)428:2<240::aid-cne4>3.0.co;2-q 11064364.

55. Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997;17(10):3727–38. 9133393.

56. Bouilleret V, Loup F, Kiener T, Marescaux C, Fritschy JM. Early loss of interneurons and delayed subunit-specific changes in GABA(A)-receptor expression in a mouse model of mesial temporal lobe epilepsy. Hippocampus. 2000;10(3):305–24. Epub 2000/07/21. doi: 10.1002/1098-1063(2000)10:3<305::AID-HIPO11>3.0.CO;2-I 10902900.

57. Magloczky Z, Freund TF. Selective neuronal death in the contralateral hippocampus following unilateral kainate injections into the CA3 subfield. Neuroscience. 1993;56(2):317–35. Epub 1993/09/01. doi: 10.1016/0306-4522(93)90334-c 8247263.

58. Chen C-MM, Orefice LL, Chiu S-LL, LeGates TA, Hattar S, Huganir RL, et al. Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice. Proceedings of the National Academy of Sciences of the United States of America. 2017;114(4). doi: 10.1073/pnas.1615792114 28069946

59. Rosso SB, Sussman D, Wynshaw-Boris A, Salinas PC. Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development. Nature neuroscience. 2005;8(1):34–42. doi: 10.1038/nn1374 15608632

60. Varela-Nallar L, Inestrosa NC. Wnt signaling in the regulation of adult hippocampal neurogenesis. Frontiers in cellular neuroscience. 2013;7:100. Epub 2013/06/28. doi: 10.3389/fncel.2013.00100 23805076; PubMed Central PMCID: PMC3693081.

61. Danzer SC. Depression, stress, epilepsy and adult neurogenesis. Experimental neurology. 2012;233(1):22–32. Epub 2011/06/21. doi: 10.1016/j.expneurol.2011.05.023 21684275; PubMed Central PMCID: PMC3199026.

62. Khalilov I, Holmes GL, Ben-Ari Y. In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures. Nature neuroscience. 2003;6(10):1079–85. Epub 2003/09/23. doi: 10.1038/nn1125 14502289.

63. Harroud A, Bouthillier A, Weil AG, Nguyen DK. Temporal lobe epilepsy surgery failures: a review. Epilepsy Res Treat. 2012;2012:201651. Epub 2012/08/31. doi: 10.1155/2012/201651 22934162; PubMed Central PMCID: PMC3420575.

64. Matsumoto R, Mikuni N, Tanaka K, Usami K, Fukao K, Kunieda T, et al. Possible induction of multiple seizure foci due to parietal tumour and anti-NMDAR antibody. Epileptic Disord. 2015;17(1):89–94; quiz Epub 2015/02/04. doi: 10.1684/epd.2015.0725 25644722.

65. Mendes A, Sampaio L. Brain magnetic resonance in status epilepticus: A focused review. Seizure. 2016;38:63–7. Epub 2016/05/09. doi: 10.1016/j.seizure.2016.04.007 27156207.

66. Houser CR. Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain research. 1990;535(2):195–204. Epub 1990/12/10. doi: 10.1016/0006-8993(90)91601-c 1705855.

67. Jessberger S, Zhao C, Toni N, Clemenson GD Jr., Li Y, Gage FH. Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. J Neurosci. 2007;27(35):9400–7. doi: 10.1523/JNEUROSCI.2002-07.2007 17728453.

68. Suzuki F, Junier MP, Guilhem D, Sorensen JC, Onteniente B. Morphogenetic effect of kainate on adult hippocampal neurons associated with a prolonged expression of brain-derived neurotrophic factor. Neuroscience. 1995;64(3):665–74. Epub 1995/02/01. doi: 10.1016/0306-4522(94)00463-f 7715779.

69. Choe Y, Pleasure SJ. Wnt signaling regulates intermediate precursor production in the postnatal dentate gyrus by regulating CXCR4 expression. Dev Neurosci. 2012;34(6):502–14. Epub 2012/12/22. doi: 10.1159/000345353 23257686.

70. Clark CE, Nourse CC, Cooper HM. The tangled web of non-canonical Wnt signalling in neural migration. Neurosignals. 2012;20(3):202–20. Epub 2012/03/30. doi: 10.1159/000332153 22456117.

71. Frotscher M, Haas CA, Forster E. Reelin controls granule cell migration in the dentate gyrus by acting on the radial glial scaffold. Cereb Cortex. 2003;13(6):634–40. Epub 2003/05/24. doi: 10.1093/cercor/13.6.634 12764039.

72. Lanoue V, Langford M, White A, Sempert K, Fogg L, Cooper HM. The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis. Scientific reports. 2017;7(1):5965. doi: 10.1038/s41598-017-06140-z 28729735

73. Yu X, Malenka RC. Beta-catenin is critical for dendritic morphogenesis. Nature neuroscience. 2003;6(11):1169–77. Epub 2003/10/07. doi: 10.1038/nn1132 14528308.

74. Chai X, Munzner G, Zhao S, Tinnes S, Kowalski J, Haussler U, et al. Epilepsy-induced motility of differentiated neurons. Cereb Cortex. 2014;24(8):2130–40. Epub 2013/03/19. doi: 10.1093/cercor/bht067 23505288.

75. Huang CT, Tao Y, Lu J, Jones JR, Fowler L, Weick JP, et al. Time-Course Gene Expression Profiling Reveals a Novel Role of Non-Canonical WNT Signaling During Neural Induction. Scientific reports. 2016;6:32600. doi: 10.1038/srep32600 27600186

76. Powell TR, Murphy T, Lee SH, Duarte RRRRR, Lee HA, Smeeth D, et al. Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood. Scientific reports. 2017;7(1):15112. doi: 10.1038/s41598-017-15042-z 29118430

77. David MD, Cantí C, Herreros J. Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling. Journal of neuroscience research. 2010;88(14):3011–23. doi: 10.1002/jnr.22464 20722074


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