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GSK-3 and Wnt Markers of Neurodevelopmental Abnormalities in Schizophrenia

  • Nitsan Kozlovsky
  • Rh Belmaker
  • Galila Agam
Part of the Neurobiological Foundation of Aberrant Behaviors book series (NFAB, volume 4)

Abstract

The Neurodevelopmental Hypothesis of schizophrenia suggests that interaction between genetic and environmental events occurring during critical early periods in neuronal growth may negatively influence the way by which nerve cells are laid down, differentiated and selectively culled by apoptosis. Recent advances offer insights into the regulation of brain development. The Wnt family of genes plays a central role in normal brain development. Activation of the Wnt cascade leads to inactivation of glycogen synthase kinase-3ß (GSK-3ß), accumulation and activation of ßcatenin and expression of genes involved in neuronal development. The possible role of aberrant GSK-3 in the etiology of schizophrenia is discussed.

Keywords

Schizophrenic Patient Neural Cell Adhesion Molecule Radiation Hybrid Mapping Neuronal Cell Adhesion Molecule Neurodevelopmental Hypothesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Anderton BH, Dayanandan R, Killick R, Lovestone S Does dysregulation of the Notch and wingless/Wnt pathways underlie the pathogenesis of Alzheimer’s disease? Mol Med Today 2000; 6: 54 - 59.PubMedCrossRefGoogle Scholar
  2. Arnold SE, Lee VM, Gur RE, Trojanowski JQ Abnormal expression of two microtubuleassociated proteins (MAP2 and MAP5) in specific subfields of the hippocampal formation in schizophrenia. Proc Natl Acad Sci USA 1991; 88: 10850 - 10854.PubMedCrossRefGoogle Scholar
  3. Arnold SE, Trojanowski JQ Recent advances in defining the neuropathology of schizophrenia. Acta Neuropathol (Berl) 1996; 92: 217 - 231.CrossRefGoogle Scholar
  4. Barbeau D, Liang JJ, Robitalille Y, Quirion R, Srivastava LK Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains. Proc Natl Acad Sci U S A 1995; 92: 2785 - 2789.PubMedCrossRefGoogle Scholar
  5. Beasley C, Cotter D, Khan N, glycogen synthase kinase-3beta immunoreactivity is reduced in the prefrontal cortex in schizophrenia.. Neurosci Lett 2001; 20: 117 - 120.CrossRefGoogle Scholar
  6. Bloom FE Advancing a neurodevelopmental origin for schizophrenia. Arch Gen Psychiatry 1993; 50: 224 - 227.PubMedCrossRefGoogle Scholar
  7. Blouin JL, Dombroski BA, Nath SK, Schizophrenia susceptibility loci on chromosomes 13832 and 8p21. Nat Genet 1998; 20: 70 - 73.PubMedCrossRefGoogle Scholar
  8. Browning MD, Dudek EM, Rapier JL, Leonard S, Freedman R Significant reductions in synapsin but not synaptophysin specific activity in the brains of some schizophrenics. Biol Psychiatry 1993; 34: 529 - 535.PubMedCrossRefGoogle Scholar
  9. Bunney BG, Potkin SG, Bunney WE, Jr. New morphological and neuropathological findings in schizophrenia: a neurodevelopmental perspective. Clin Neurosci 1995; 3: 81 - 88.PubMedGoogle Scholar
  10. Cohen P The role of protein phosphorylation in the hormonal control of enzyme activity. Eur J Biochem 1985; 151:439-448.274Google Scholar
  11. Conrad Ai, Scheibel AB Schizophrenia and the hippocampus: the embryological hypothesis extended. Schizophr Bull 1987; 13: 577 - 587.PubMedCrossRefGoogle Scholar
  12. Cotter D, Kerwin R, al-Sarraji S, Abnormalities of Wnt signalling in schizophrenia-evidence for neurodevelopmental abnormality. Neuroreport 1998; 9: 1379 - 1383.PubMedCrossRefGoogle Scholar
  13. Cotter D, Kerwin R, Doshi B, Martin CS, Everall IP Alterations in hippocampal nonphosphorylated MAP2 protein expression in schizophrenia. Brain Res 1997; 765: 238246.Google Scholar
  14. Dominguez I, Itoh K, Sokol SY Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos. Proc Natl Acad Sci U S A 1995; 92: 8498 - 8502.PubMedCrossRefGoogle Scholar
  15. Frame S, Cohen P, Biondi RM A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell 2001; 7: 1321 - 1327.PubMedCrossRefGoogle Scholar
  16. Garcia-Perez J, Avila J, Diaz-Nido J Implication of cyclin-dependent kinases and glycogen synthase kinase 3 in the phosphorylation of microtubule-associated protein 1B in developing neuronal cells. J Neurosci Res 1998; 52: 445 - 452.Google Scholar
  17. Glantz LA, Lewis DA Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity [corrected and republished article originally appeared in Arch Gen Psychiatry 1997 Jul;54(7):660-669]. Arch Gen Psychiatry 1997; 54: 943 - 952.CrossRefGoogle Scholar
  18. Goold RG, Owen R, Gordon-Weeks PR Glycogen synthase kinase 3beta phosphorylation of microtubule-associated protein IB regulates the stability of microtubules in growth cones. J Cell Sci 1999; 112: 3373 - 3384.PubMedGoogle Scholar
  19. Hall AC, Lucas FR, Salinas PC Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling [see comments]. Cell 2000; 100: 525 - 535.PubMedCrossRefGoogle Scholar
  20. Hanger DP, Hughes K, Woodgett JR, Brion JP, Anderton BH Glycogen synthase kinase-3 induces Alzheimer’s disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci Lett 1992; 147: 5862.CrossRefGoogle Scholar
  21. Harrison PJ The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 1999; 122: 593 - 624.PubMedCrossRefGoogle Scholar
  22. He X, Saint-Jeannet JP, Woodgett JR, Varmus HE, Dawid IB Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos [published erratum appears in Nature 1995 May 18;375(6528):253]. Nature 1995; 374: 617 - 622.PubMedCrossRefGoogle Scholar
  23. Hemperly JJ, Murray BA, Edelman GM, Cunningham BA Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM [published erratum appears in Proc Natl Acad Sci U S A 1988 Mar;85(6):2008]. Proc Natl Acad Sci U S A 1986; 83: 3037 - 3041.Google Scholar
  24. Impagnatiello F, Guidotti AR, Pesold C, A decrease of reelin expression as a putativeGoogle Scholar
  25. vulnerability factor in schizophrenia. Proc Natl Acad Sci USA 1998; 95: 15718 - 15723.Google Scholar
  26. Kozlovsky N, Belmaker RH, Agam G Low GSK-3beta immunoreactivity in postmortem frontal cortex of schizophrenic patients. Am J Psychiatry 2000; 157: 831 - 833.PubMedCrossRefGoogle Scholar
  27. Kozlovsky N, Belmaker RH, Agam G Low GSK-3 activity in frontal cortex of schizophrenic patients. Schizo Res 2001; in pressGoogle Scholar
  28. Landmesser L, Dahm L, Tang JC, Rutishauser U Polysialic acid as a regulator of intramuscular nerve branching during embryonic development. Neuron 1990; 4: 655667.Google Scholar
  29. Lijam N, Paylor R, McDonald MP, Social interaction and sensorimotor gating abnormalities in mice lacking Dvll. Cell 1997; 90: 895 - 905.PubMedCrossRefGoogle Scholar
  30. Mandelkow EM, Drewes G, Biemat J, Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett 1992; 314: 315 - 321.PubMedCrossRefGoogle Scholar
  31. Manschreck TC, Maher BA, Winzig L, Candela SF, Beaudette S, Boshes R Age disorientation in schizophrenia: an indicator of progressive and severe psychopathology, not institutional isolation. J Neuropsychiatry Clin Neurosci 2000; 12: 350 - 358.PubMedCrossRefGoogle Scholar
  32. Mates A, Riederer B Microtubule-associated proteins in the developing brain. Ann N Y Acad Sci 1986; 466: 167-179. 275Google Scholar
  33. McCarley RW, Wible CG, Frumin M, MRI anatomy of schizophrenia. Biol Psychiatry 1999; 45: 1099 - 1119.PubMedCrossRefGoogle Scholar
  34. McClain DA, Edelman GM A neural cell adhesion molecule from human brain. Proc Natl Acad Sci U S A 1982; 79: 6380 - 6384.PubMedCrossRefGoogle Scholar
  35. McMahon AP, Bradley A The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 1990; 62: 1073 - 1085.PubMedCrossRefGoogle Scholar
  36. Miyaoka T, Seno H, Ishino H Increased expression of Wnt-1 in schizophrenic brains. Schizophr Res 1999; 38: 1 - 6.PubMedCrossRefGoogle Scholar
  37. Moon RT, Brown JD, Tones M WNTs modulate cell fate and behavior during vertebrate development. Trends Genet 1997; 13: 157 - 162.PubMedCrossRefGoogle Scholar
  38. Murray RM Neurodevelopmental schizophrenia: the rediscovery of dementia praecox. Br J Psychiatry S uppl 1994;:6-12.Google Scholar
  39. Patapoutian A, Reichardt LF Roles of wnt proteins in neural development and maintenance [In Process Citation]. Curr Opin Neurobiol 2000; 10: 392 - 399.PubMedCrossRefGoogle Scholar
  40. Pei JJ, Braak E, Braak H, Distribution of active glycogen synthase kinase 3beta (GSK3beta) in brains staged for Alzheimer disease neurofibrillary changes. J Neuropathol Exp Neurol 1999; 58: 1010 - 1019.PubMedCrossRefGoogle Scholar
  41. Pizzuti A, Novelli G, Mari A, Human homologue sequences to the Drosophila dishevelled segment-polarity gene are deleted in the DiGeorge syndrome. Am J Hum Genet 1996; 58: 722 - 729.PubMedGoogle Scholar
  42. Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR Glycogen synthase kinase-3:Google Scholar
  43. functions in oncogenesis and development. Biochim Biophys Acta 1992; 1114: 147-162. Rhoads AR, Karkera JD, Detera-Wadleigh SD Radiation hybrid mapping of genes in theGoogle Scholar
  44. lithium-sensitive wnt signaling pathway. Mol Psychiatry 1999; 4: 437 - 442.Google Scholar
  45. Roberts GW Schizophrenia: the cellular biology of a functional psychosis. Trends Neurosci 1990; 13:207-211.Google Scholar
  46. Robinson WP, Waslynka J, Bernasconi F, Delineation of 7g11.2 deletions associated with Williams-Beuren syndrome and mapping of a repetitive sequence to within and to either side of the common deletion. Genomics 1996; 34: 17 - 23.PubMedCrossRefGoogle Scholar
  47. Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly [see comments]. Science 1996; 272: 1023 - 1056.PubMedCrossRefGoogle Scholar
  48. Shaw PC, Davies AF, Lau KF, Isolation and chromosomal mapping of human glycogen synthase kinase-3 alpha and -3 beta encoding genes. Genome 1998; 41: 720 - 727.PubMedGoogle Scholar
  49. Siegfried E, Chou TB, Perrimon N wingless signaling acts through zeste-white 3, the Drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate. Cell 1992; 71: 1167 - 1179.PubMedCrossRefGoogle Scholar
  50. Sower AC, Bird ED, Perrone-Bizzozero NI Increased levels of GAP-43 protein in schizophrenic brain tissues demonstrated by a novel immunodetection method. Mol Chem Neuropathol 1995; 24: 1 - 11.PubMedCrossRefGoogle Scholar
  51. Srivastava AK, Pandey SK Potential mechanism(s) involved in the regulation of glycogen synthesis by insulin. Mol Cell Biochem 1998; 182: 135 - 141.PubMedCrossRefGoogle Scholar
  52. Stambolic V, Woodgett JR Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem J 1994; 303: 701 - 704.PubMedGoogle Scholar
  53. Torrey EF, Webster M, Knable M, Johnston N, Yolken RH The stanley foundation brain collection and neuropathology consortium. Schizophr Res 2000; 44: 151 - 155.PubMedCrossRefGoogle Scholar
  54. van Kammen DP, Poltorak M, Kelley ME, Further studies of elevated cerebrospinal fluid neuronal cell adhesion molecule in schizophrenia. Biol Psychiatry 1998; 43: 680 - 686.PubMedCrossRefGoogle Scholar
  55. Vawter MP, Cannon-Spoor HE, Hemperly JJ, Abnormal expression of cell recognition molecules in schizophrenia Exp Neurol 1998; 149: 424 - 432.Google Scholar
  56. Wang QM, Roach PJ, Fiol CJ Use of a synthetic peptide as a selective substrate for glycogen synthase kinase 3. Anal Biochem 1994; 220: 397 - 402.PubMedCrossRefGoogle Scholar
  57. Wang Y, Macke JP, Abella BS, A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. J Biol Chem 1996; 271: 4468-4476. 276Google Scholar
  58. Wei J, Hemmings GP The NOTCH4 locus is associated with susceptibility to schizophrenia. Nat Genet 2000; 25: 376 - 7.PubMedCrossRefGoogle Scholar
  59. Weinberger DR Implications of normal brain development for the pathogenesis of schizophrenia Arch Gen Psychiatry 1987; 44:660-669.Google Scholar
  60. Weston CR, Davis RJ Signal transduction: signaling specificity-a complex affair. Science 2001; 292: 2439 - 2440.PubMedCrossRefGoogle Scholar
  61. Wodarz A, Nusse R Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol 1998; 14: 59 - 88.PubMedCrossRefGoogle Scholar
  62. Woodgett JR Molecular cloning and expression of glycogen synthase kinase-3/factor A. Embo J 1990; 9: 2431 - 2438.Google Scholar
  63. Woodgett JR A common denominator linking glycogen metabolism, nuclear oncogenes and development. Trends Biochem Sci 1991; 16: 177 - 181.CrossRefGoogle Scholar
  64. Yang SD, Huang JJ, Huang TJ Protein kinase FA/glycogen synthase kinase 3 alpha predominantly phosphorylates the in vivo sites of Ser502, Ser506, Ser603, and Ser666 in neurofilament. J Neurochem 1995a; 64: 1848 - 1854.PubMedCrossRefGoogle Scholar
  65. Yang SD, Song JS, Hsieh YT, Liu HW, Chan WH Identification of the ATP.Mg-dependent protein phosphatase activator (FA) as a synapsin I kinase that inhibits cross-linking of synapsin I with brain microtubules. J Protein Chem 1992; 11: 539 - 546.PubMedCrossRefGoogle Scholar
  66. Yang SD, Yu JS, Lee TT, Yang CC, Ni MH, Yang YY Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder. J Cell Biochem 1995b; 59: 108 - 116.PubMedCrossRefGoogle Scholar
  67. Yu JS, Yang SD Immunological and biochemical study on tissue and subcellular distributions of protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase): a simplified and efficient procedure for high quantity purification from brain. J Protein Chem 1993; 12: 667 - 676.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Nitsan Kozlovsky
  • Rh Belmaker
  • Galila Agam

There are no affiliations available

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