Schizophrenia Research
Volume 91, Issue 1 , Pages 51-61 , March 2007

Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder

Received 3 August 2006 ,Revised 17 November 2006 ,Accepted 26 November 2006.

References 

  1. Abdolmaleky HM, Cheng KH, Russo A, Smith CL, Faraone SV, Wilcox M, et al. Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: a preliminary report. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005;134(1):60–66
  2. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE, et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch. Gen. Psychiatry. 1995;52(4):258–266
  3. Aleman A, Kahn RS. Strange feelings: do amygdala abnormalities dysregulate the emotional brain in schizophrenia?. Prog. Neurobiol. 2005;77(5):283–298
  4. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. Fourth edition. Washington, DC: American Psychiatric Association; 1994;
  5. Barbas H, De Olmos J. Projections from the amygdala to basoventral and mediodorsal prefrontal regions in the rhesus monkey. J. Comp. Neurol. 1990;300(4):549–571
  6. Beffert U, Weeber EJ, Durudas A, Qiu S, Masiulis I, Sweatt JD, et al. Modulation of synaptic plasticity and memory by reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron. 2005;47(4):567–579
  7. Benes FM, Berretta S. GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology. 2001;25(1):1–27
  8. Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP. Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics. J. Neurosci. 1992;12(3):924–929
  9. Benes FM, Matzilevich D, Burke RE, Walsh J. The expression of proapoptosis genes is increased in bipolar disorder, but not in schizophrenia. Mol. Psychiatry. 2006;11(3):241–251
  10. Brueckner B, Lyko F. DNA methyltransferase inhibitors: old and new drugs for an epigenetic cancer therapy. Trends Pharmacol. Sci. 2004;25(11):551–554
  11. Carboni G, Tueting P, Tremolizzo L, Sugaya I, Davis J, Costa E, et al. Enhanced dizocilpine efficacy in heterozygous reeler mice relates to GABA turnover downregulation. Neuropharmacology. 2004;46(8):1070–1081
  12. Chen Y, Sharma RP, Costa RH, Costa E, Grayson DR. On the epigenetic regulation of the human reelin promoter. Nucleic Acids Res. 2002;30(13):2930–2939
  13. Costa E, Davis J, Grayson DR, Guidotti A, Pappas GD, Pesold C. Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability. Neurobiol. Dis. 2001;8(5):723–742
  14. Costa E, Chen Y, Davis JM, Dong E, Noh JS, Tremolizzo L, et al. Reelin and schizophrenia: a disease at the interface of the genome and the epigenome. Mol. Interv. 2002;2(1):47–57
  15. Costa E, Grayson DR, Guidotti A. Epigenetic downregulation of GABAergic function in schizophrenia: potential for pharmacological intervention?. Mol. Interv. 2003;3(4):220–229
  16. Costa E, Grayson DR, Mitchell CP, Tremolizzo L, Veldic M, Guidotti A. GABAergic cortical neuron chromatin as a putative target to treat schizophrenia vulnerability. Crit. Rev. Neurobiol. 2003;15(2):121–142
  17. Detich N, Bovenzi V, Szyf M. Valproate induces replication-independent active DNA demethylation. J. Biol. Chem. 2003;278(30):27586–27592
  18. Dong E, Caruncho H, Liu WS, Smalheiser NR, Grayson DR, Costa E, et al. A reelin-integrin interaction regulates Arc mRNA translation in synaptoneurosomes. Proc. Natl. Acad. Sci. U. S. A. 2003;100(9):5479–5484
  19. Dong E, Agis-Balboa RC, Simonini MV, Grayson DR, Costa E, Guidotti A. Reelin and glutamic acid decarboxylase67 promoter remodeling in an epigenetic methionine-induced mouse model of schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 2005;102(35):12578–12583
  20. Eastwood SL, Harrison PJ. Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Mol. Psychiatry. 2003;8(9):821–831
  21. Fatemi SH, Earle JA, McMenomy T. Reduction in reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol. Psychiatry. 2000;5(6):654–663
  22. Feighner JP, Robins E, Guze SB, Woodruff RA, Winokur G, Munoz R. Diagnostic criteria for use in psychiatric research. Arch. Gen. Psychiatry. 1972;26(1):57–63
  23. Gabbott PL, Somogyi P. Quantitative distribution of GABA-immunoreactive neurons in the visual cortex (area 17) of the cat. Exp. Brain Res. 1986;61(2):323–331
  24. Grayson DR, Jia X, Chen Y, Sharma RP, Mitchell CP, Guidotti A, et al. Reelin promoter hypermethylation in schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 2005;102(26):9341–9346
  25. Grayson DR, Chen Y, Costa E, Dong E, Guidotti A, Kundakovic M, et al. The human reelin gene: transcription factors (+), repressors (−) and the methylation switch (+/−) in schizophrenia. Pharmacol. Ther. 2006;111(1):272–286
  26. Guidotti A, Auta J, Davis JM, Di-Giorgi-Gerevini V, Dwivedi Y, Grayson DR, et al. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch. Gen. Psychiatry. 2000;57(11):1061–1069
  27. Guidotti A, Auta J, Davis JM, Dong E, Grayson DR, Veldic M, et al. GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon. Psychopharmacology (Berl). 2005;180(2):191–205
  28. Hanada S, Mita T, Nishino N, Tanaka C. [3H]muscimol binding sites increased in autopsied brains of chronic schizophrenics. Life Sci. 1987;40(3):259–266
  29. Hong EJ, West AE, Greenberg ME. Transcriptional control of cognitive development. Curr. Opin. Neurobiol. 2005;15(1):21–28
  30. Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, et al. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 1998;95(26):15718–15723
  31. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293(5532):1074–1080
  32. Kemp JM, Powell TP. The cortico-striate projection in the monkey. Brain. 1970;93(3):525–546
  33. Kunzle H. Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia. An autoradiographic study in Macaca fascicularis. Brain Res. 1975;88(2):195–209
  34. Larson J, Hoffman JS, Guidotti A, Costa E. Olfactory discrimination learning deficit in heterozygous reeler mice. Brain Res. 2003;971(1):40–46
  35. Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat. Rev. Neurosci. 2005;6(4):312–324
  36. Liu WS, Pesold C, Rodriguez MA, Carboni G, Auta J, Lacor P, et al. Downregulation of dendritic spine and glutamic acid decarboxylase67 expressions in reelin haploinsufficient heterozygous reeler mouse. Proc. Natl. Acad. Sci. U. S. A. 2001;98(6):3477–3482
  37. Mitchell CP, Chen Y, Kundakovic M, Costa E, Grayson DR. Histone deacetylase inhibitors decrease reelin promoter methylation in vitro. J. Neurochem. 2005;93(2):483–492
  38. Noh JS, Sharma R, Veldic M, Salvacion AA, Jia X, Chen Y, et al. DNA methyltransferase 1 regulates reelin mRNA expression in mouse primary cortical cultures. Proc. Natl. Acad. Sci. U. S. A. 2005;102(5):1749–1754
  39. Parent A, Hazrati LN. Functional anatomy of the basal ganglia. I. The cortico-basal ganglia thalamo-cortical loop. Brain Res. Brain Res. Rev. 1995;20(1):91–127
  40. Popken GJ, Bunney Jr. WE, Potkin SG, Jones EG. Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. Proc. Natl. Acad. Sci. U. S. A. 2000;97(16):9276–9280
  41. Qiu S, Korwek KM, Pratt-Davis AR, Peters M, Bergman MY, Weeber EJ. Cognitive disruption and altered hippocampus synaptic function in reelin haploinsufficient mice. Neurobiol. Learn. Mem. 2006;85(3):228–242
  42. Rajkowska G, Goldman-Rakic PS. Cytoarchitectonic definition of prefrontal areas in the normal human cortex: I Remapping of areas 9 and 46 using quantitative criteria. Cereb. Cortex. 1995;5(4):307–332
  43. Robertson AK, Geiman TM, Sankpal UT, Hager GL, Robertson KD. Effects of chromatin structure on the enzymatic and DNA binding functions of DNA methyltransferases DNMT1 and Dnmt3a in vitro. Biochem. Biophys. Res. Commun. 2004;322(1):110–118
  44. Rodriguez MA, Caruncho HJ, Costa E, Pesold C, Liu WS, Guidotti A. In Patas monkey, glutamic acid decarboxylase-67 and reelin mRNA coexpression varies in a manner dependent on layers and cortical areas. J. Comp. Neurol. 2002;451(3):279–288
  45. Rotaru DC, Barrionuevo G, Sesack SR. Mediodorsal thalamic afferents to layer III of the rat prefrontal cortex: synaptic relationships to subclasses of interneurons. J. Comp. Neurol. 2005;490(3):220–238
  46. Ruzicka, W.B., Zhubi, A., Veldic, M., Grayson, D.R., Costa, E., Guidotti, A., in press. Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection. Mol. Psychiatry.
  47. Selemon LD, Goldman-Rakic PS. Longitudinal topography and interdigitation of cortico-striatal projections in the rhesus monkey. J. Neurosci. 1985;5(3):776–794
  48. Simonini MV, Camargo LM, Dong E, Maloku E, Veldic M, Costa E, et al. The benzamide MS-275 is a potent long-lasting brain region-selective inhibitor of histone deacetylases. Proc. Natl. Acad. Sci. U. S. A. 2006;103(5):1587–1592
  49. Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J. Psychosom. Res. 2002;53(2):647–654
  50. Tisch S, Silberstein P, Limousin-Dowsey P, Jahanshahi M. The basal ganglia: anatomy physiology and pharmacology. Psychiatr. Clin. North Am. 2004;27(4):757–799
  51. Tremolizzo L, Carboni G, Ruzicka WB, Mitchell CP, Sugaya I, Tueting P, et al. An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Proc. Natl. Acad. Sci. U. S. A. 2002;99(26):17095–17100
  52. Tremolizzo L, Doueiri MS, Dong E, Grayson DR, Davis J, Pinna G, et al. Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice. Biol. Psychiatry. 2005;57(5):500–509
  53. Veldic M, Caruncho HJ, Liu WS, Davis J, Satta R, Grayson DR, et al. DNA methyltransferase 1 is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc. Natl. Acad. Sci. U. S. A. 2004;101(1):348–353
  54. Veldic M, Guidotti A, Maloku E, Davis JM, Costa E. In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc. Natl. Acad. Sci. U. S. A. 2005;102(6):2152–2157
  55. Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA. Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch. Gen. Psychiatry. 2000;57(3):237–245
  56. Woo TU, Walsh JP, Benes FM. Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. Arch. Gen. Psychiatry. 2004;61(7):649–657

PII: S0920-9964(06)00493-2

doi: 10.1016/j.schres.2006.11.029

Schizophrenia Research
Volume 91, Issue 1 , Pages 51-61 , March 2007