The glutamatergic aspects of schizophrenia molecular pathophysiology: Role of the postsynaptic density, and implications for treatment

Current Neuropharmacology

Volumn 12, Issue 3, 2014, Pages 219-238

  Iasevoli, Felice ^a   Tomasetti, Carmine ^a   Buonaguro, Elisabetta F ^a   de Bartolomeis, Andrea ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Dopamine; Homer; Kalirin; NMDA; PSD 95; Psychosis; Shank; Synaptic plasticity

Indexed keywords

ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CYCLIC AMP DEPENDENT PROTEIN KINASE ANCHORING PROTEIN; DIACYLGLYCEROL; ENA VASP HOMOLOGY 1 DOMAIN; EPHRIN RECEPTOR; GLUTAMATE RECEPTOR INTERACTING PROTEIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANYLATE KINASE; INOSITOL TRISPHOSPHATE 3 KINASE; IONOTROPIC RECEPTOR; KALIRIN; METABOTROPIC RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PDZ PROTEIN; PHOSPHATIDYLINOSITOL KINASE; POSTSYNAPTIC DENSITY PROTEIN 95; PROTEIN; PROTEIN HOMER; RAC1 PROTEIN; SCAFFOLD PROTEIN; SHANK PROTEIN; TRANSIENT RECEPTOR POTENTIAL CHANNEL; TRP ANKYRIN REPEAT AND COILED COIL REGION CONTAINING PROTEIN; UNCLASSIFIED DRUG; VOLTAGE GATED CALCIUM CHANNEL;

ARTICLE; CALCIUM TRANSPORT; CHROMOSOME PAIRING; CLINICAL TRIAL (TOPIC); HUMAN; NERVE CELL EXCITABILITY; NERVE CELL PLASTICITY; NEUROTRANSMISSION; NONHUMAN; POSTSYNAPTIC DENSITY; PROTEIN EXPRESSION; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; SODIUM TRANSPORT;

EID: 84924135008     PISSN: 1570159X     EISSN: 18756190     Source Type: Journal    
DOI: 10.2174/1570159X12666140324183406     Document Type: Article

References (199)

1. Leucht, S.; Corves, C.; Arbter, D.; Engel, R. R.; Li, C.; Davis, J. M. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet, 2009, 373 (9657), 31-41. doi:10.1016/S0140-6736(08)61764-X
2. Snyder, M. A.; Gao, W. J. NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Front. Cell Neurosci., 2013, 7, 31. doi.org/10.3389/fncel.2013.00031
3. Schwartz, T. L.; Sachdeva, S.; Stahl, S. M. Glutamate neurocircuitry: theoretical underpinnings in schizophrenia. Front. Pharmacol., 2012, 3, 195. doi.org/10.3389/fphar.2012.00195
4. Schwartz, T. L.; Sachdeva, S.; Stahl, S. M. Genetic data supporting the NMDA glutamate receptor hypothesis for schizophrenia. Curr. Pharm. Des., 2012, 18 (12), 1580-92. doi.org/10.3389/fphar.2012. 00195
5. Javitt, D. C. Twenty-five years of glutamate in schizophrenia: are we there yet? Schizophr. Bull., 2012, 38 (5), 911-3. doi.org/10. 1093/schbul/sbs100
6. Coyle, J. T.; Basu, A.; Benneyworth, M.; Balu, D.; Konopaske, G. Glutamatergic synaptic dysregulation in schizophrenia: therapeutic implications. Handb. Exp. Pharmacol., 2012, (213), 267-95. doi.org/10.1007/978-3-642-25758-2_10
7. Moghaddam, B.; Krystal, J. H. Capturing the angel in "angel dust": twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans. Schizophr. Bull., 2012, 38 (5), 942-9. doi.org/10.1093/schbul/sbs075
8. Field, J. R.; Walker, A. G.; Conn, P. J. Targeting glutamate synapses in schizophrenia. Trends Mol. Med., 2011, 17 (12), 689- 98. doi.org/10.1016/j.molmed.2011.08.004
9. Kew, J. N.; Kemp, J. A., Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl), 2005, 179 (1), 4-29. doi.org/10.1007/s00213-005-2200-z
10. Kew, J. N.; Koester, A.; Moreau, J. L.; Jenck, F.; Ouagazzal, A. M.; Mutel, V.; Richards, J. G.; Trube, G.; Fischer, G.; Montkowski, A.; Hundt, W.; Reinscheid, R. K.; Pauly-Evers, M.; Kemp, J. A.; Bluethmann, H., Functional consequences of reduction in NMDA receptor glycine affinity in mice carrying targeted point mutations in the glycine binding site. J. Neurosci., 2000, 20 (11), 4037-49. PMID:10818139
11. Anson, L. C.; Chen, P. E.; Wyllie, D. J.; Colquhoun, D.; Schoepfer, R. Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors. J. Neurosci., 1998, 18 (2), 581-9. PMID: 9425000
12. Iasevoli, F.; Tomasetti, C.; de Bartolomeis, A. Scaffolding proteins of the post-synaptic density contribute to synaptic plasticity by regulating receptor localization and distribution: relevance for neuropsychiatric diseases. Neurochem. Res., 2013, 38 (1), 1-22. doi.org/10.1007/s11064-012-0886-y
13. Verpelli, C.; Schmeisser, M. J.; Sala, C.; Boeckers, T. M. Scaffold proteins at the postsynaptic density. Adv. Exp. Med. Biol., 2012, 970, 29-61. doi.org/10.1007/978-3-7091-0932-8_2
14. Sheng, M.; Hoogenraad, C. C. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu. Rev. Biochem. 2007, 76, 823-47. doi.org/10.1146/annurev.biochem.76.060805. 160029
15. Benarroch, E. E. NMDA receptors: recent insights and clinical correlations. Neurology, 2011, 76 (20), 1750-7. doi.org/10.1212/ WNL.0b013e31821b7cc9
16. Priestley, T.; Kemp, J. A. Kinetic study of the interactions between the glutamate and glycine recognition sites on the N-methyl-Daspartic acid receptor complex. Mol. Pharmacol., 1994, 46 (6), 1191- 6. PMID: 7808441
17. Monaghan, D. T.; Jane, D. E. Pharmacology of NMDA Receptors. 2009.
18. Javitt, D. C.; Zukin, S. R.; Heresco-Levy, U.; Umbricht, D. Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophr. Bull., 2012, 38 (5), 958-66. doi.org/10.1093/schbul/sbs069
19. Francotte, P.; de Tullio, P.; Fraikin, P.; Counerotte, S.; Goffin, E.; Pirotte, B. In search of novel AMPA potentiators. Recent Pat CNS Drug Discov., 2006, 1 (3), 239-46. doi.org/10.2174/ 157488906778773661
20. O'Neill, M. J.; Bleakman, D.; Zimmerman, D. M.; Nisenbaum, E. S. AMPA receptor potentiators for the treatment of CNS disorders. Curr. Drug Targets CNS Neuro. Disord., 2004, 3 (3), 181-94. doi.org/10.2174/1568007043337508
21. Arai, A. C.; Kessler, M. Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Curr. Drug Targets, 2007, 8 (5), 583-602. doi.org/10.2174/138945007780618490
22. Jane, D. E.; Lodge, D.; Collingridge, G. L. Kainate receptors: pharmacology, function and therapeutic potential. Neuropharmacology, 2009, 56 (1), 90-113. doi.org/10.1016/j.neuropharm. 2008.08.023
23. Pin, J. P.; Acher, F. The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr. Drug Targets CNS Neurol. Disord., 2002, 1 (3), 297-317. doi.org/ 10.2174/1568007023339328
24. Pisani, A.; Bonsi, P.; Centonze, D.; Bernardi, G.; Calabresi, P. Functional coexpression of excitatory mGluR1 and mGluR5 on striatal cholinergic interneurons. Neuropharmacology, 2001, 40 (3), 460-3. doi.org/10.1016/S0028-3908(00)00184-2
25. Pisani, A.; Gubellini, P.; Bonsi, P.; Conquet, F.; Picconi, B.; Centonze, D.; Bernardi, G.; Calabresi, P. Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons. Neuroscience, 2001, 106 (3), 579-87. doi.org/10.1016/S0306-4522(01)00297-4
26. Benarroch, E. E. Metabotropic glutamate receptors: synaptic modulators and therapeutic targets for neurologic disease. Neurology, 2008, 70 (12), 964-8. doi.org/10.1212/01.wnl.0000306315.03021.2a
27. Marek, G. J. Metabotropic glutamate2/3 (mGlu2/3) receptors, schizophrenia and cognition. Eur. J. Pharmacol., 2010, 639 (1-3), 81-90. doi.org/10.1016/j.ejphar.2010.02.058
28. Cartmell, J.; Schoepp, D. D. Regulation of neurotransmitter release by metabotropic glutamate receptors. J. Neurochem., 2000, 75 (3), 889-907. doi.org/10.1046/j.1471-4159.2000.0750889.x
29. Kim, J. S.; Kornhuber, H. H.; Brand, U.; Menge, H. G. Effects of chronic amphetamine treatment on the glutamate concentration in cerebrospinal fluid and brain: implications for a theory of schizophrenia. Neurosci. Lett., 1981, 24 (1), 93-6. doi.org/10.1016/ 0304-3940(81)90365-7
30. Lodge, D.; Anis, N. A. Effects of phencyclidine on excitatory amino acid activation of spinal interneurones in the cat. Eur. J. Pharmacol., 1982, 77 (2-3), 203-4. doi.org/10.1016/0014-2999(82) 90022-X
31. Luby, E. D.; Cohen, B. D.; Rosenbaum, G.; Gottlieb, J. S.; Kelley, R. Study of a new schizophrenomimetic drug; sernyl. AMA Arch. Neurol. Psychiatry, 1959, 81 (3), 363-9. doi.org/10.1001/ archneurpsyc.1959.02340150095011
32. Rosenbaum, G.; Cohen, B. D.; Luby, E. D.; Gottlieb, J. S.; Yelen, D. Comparison of sernyl with other drugs: simulation of schizophrenic performance with sernyl, LSD-25, and amobarbital (amytal) sodium; I. Attention, motor function, and proprioception. AMA Arch. Gen. Psychiatry, 1959, 1, 651-6. doi.org/10.1001/ archpsyc.1959.03590060113013
33. Javitt, D. C., Negative schizophrenic symptomatology and the PCP (phencyclidine) model of schizophrenia. Hillside J. Clin. Psychiatry, 1987, 9 (1), 12-35. PMID: 2820854
34. Krystal, J. H.; Karper, L. P.; Seibyl, J. P.; Freeman, G. K.; Delaney, R.; Bremner, J. D.; Heninger, G. R.; Bowers, M. B., Jr.; Charney, D. S. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch. Gen. Psychiatry, 1994, 51 (3), 199-214. doi.org/10.1001/archpsyc.1994.03950030035004
35. Lahti, A. C.; Holcomb, H. H.; Medoff, D. R.; Tamminga, C. A. Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport, 1995, 6 (6), 869-72. doi.org/10.1097/ 00001756-199504190-00011
36. Malhotra, A. K.; Pinals, D. A.; Adler, C. M.; Elman, I.; Clifton, A.; Pickar, D.; Breier, A. Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology, 1997, 17 (3), 141-50. doi.org/10.1016/ S0893-133X(97)00036-5
37. Kesner, R. P.; Hardy, J. D.; Calder, L. D. Phencyclidine and behavior: I. Sensory-motor function, activity level, taste aversion and water intake. Pharmacol. Biochem. Behav., 1981, 15 (1), 7-13. doi.org/10.1016/0091-3057(81)90330-0
38. Jentsch, J. D.; Taylor, J. R.; Roth, R. H. Subchronic phencyclidine administration increases mesolimbic dopaminergic system responsivity and augments stress- and psychostimulant-induced hyperlocomotion. Neuropsychopharmacology, 1998, 19 (2), 105- 13. doi.org/10.1016/S0893-133X(98)00004-9
39. Tricklebank, M. D.; Singh, L.; Oles, R. J.; Preston, C.; Iversen, S. D. The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. Eur. J. Pharmacol., 1989, 167 (1), 127-35. doi.org/10.1016/0014- 2999(89)90754-1
40. Verma, A.; Moghaddam, B. NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine. J. Neurosci., 1996, 16 (1), 373-9. PMID: 8613804
41. Johansson, C.; Jackson, D. M.; Svensson, L. The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat. Psychopharmacology, (Berl) 1994, 116 (4), 437-42. doi.org/10.1007/BF02247475
42. Corbett, R.; Camacho, F.; Woods, A. T.; Kerman, L. L.; Fishkin, R. J.; Brooks, K.; Dunn, R. W. Antipsychotic agents antagonize noncompetitive N-methyl-D-aspartate antagonist-induced behaviors. Psychopharmacology (Berl), 1995, 120 (1), 67-74. doi.org/10.1007/ BF02246146
43. Sams-Dodd, F. Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia. Behav. Pharmacol., 1996, 7 (1), 3-23. doi.org/10.1097/00008877- 199601000-00001
44. Lipska, B. K.; Weinberger, D. R. To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology, 2000, 23 (3), 223-39. doi.org/10.1016/S0893-133X(00)00137-8
45. Olney, J. W.; Farber, N. B. Glutamate receptor dysfunction and schizophrenia. Arch. Gen. Psychiatry, 1995, 52 (12), 998-1007. doi.org/10.1001/archpsyc.1995.03950240016004
46. Newcomer, J. W.; Farber, N. B.; Jevtovic-Todorovic, V.; Selke, G.; Melson, A. K.; Hershey, T.; Craft, S.; Olney, J. W. Ketamineinduced NMDA receptor hypofunction as a model of memory impairment and psychosis. Neuropsychopharmacology, 1999, 20 (2), 106-18. doi.org/10.1016/S0893-133X(98)00067-0
47. Olney, J. W.; Newcomer, J. W.; Farber, N. B. NMDA receptor hypofunction model of schizophrenia. J. Psychiatr. Res., 1999, 33 (6), 523-33. doi.org/10.1016/S0022-3956(99)00029-1
48. Weickert, C. S.; Fung, S. J.; Catts, V. S.; Schofield, P. R.; Allen, K. M.; Moore, L. T.; Newell, K. A.; Pellen, D.; Huang, X. F.; Catts, S. V.; Weickert, T. W. Molecular evidence of N-methyl-D-aspartate receptor hypofunction in schizophrenia. Mol. Psychiatry, 2012,18, 1185-92. doi.org/10.1038/mp.2012.137
49. Ibrahim, H. M.; Hogg, A. J., Jr.; Healy, D. J.; Haroutunian, V.; Davis, K. L.; Meador-Woodruff, J. H., Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia. Am. J. Psychiatry, 2000, 157 (11), 1811-23. doi.org/10.1176/appi.ajp.157.11.1811
50. Clinton, S. M.; Haroutunian, V.; Davis, K. L.; Meador-Woodruff, J. H. Altered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophrenia. Am. J. Psychiatry, 2003, 160 (6), 1100-9. doi.org/10.1176/appi.ajp. 160.6.1100
51. Beneyto, M.; Kristiansen, L. V.; Oni-Orisan, A.; McCullumsmith, R. E.; Meador-Woodruff, J. H. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology, 2007, 32 (9), 1888-902. doi.org/10.1038/sj.npp.1301312
52. Beneyto, M.; Meador-Woodruff, J. H. Lamina-specific abnormalities of NMDA receptor-associated postsynaptic protein transcripts in the prefrontal cortex in schizophrenia and bipolar disorder. Neuropsychopharmacology, 2008, 33 (9), 2175-86. doi.org/10. 1038/sj.npp.1301604
53. Vrajova, M.; Stastny, F.; Horacek, J.; Lochman, J.; Sery, O.; Pekova, S.; Klaschka, J.; Hoschl, C., Expression of the hippocampal NMDA receptor GluN1 subunit and its splicing isoforms in schizophrenia: postmortem study. Neurochem Res 2010, 35 (7), 994-1002. doi.org/10.1007/s11064-010-0145-z
54. McCullumsmith, R. E.; Kristiansen, L. V.; Beneyto, M.; Scarr, E.; Dean, B.; Meador-Woodruff, J. H. Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain Res., 2007, 1127 (1), 108-18. doi.org/10.1016/ j.brainres.2006.09.011
55. Clinton, S. M.; Meador-Woodruff, J. H. Abnormalities of the NMDA Receptor and Associated Intracellular Molecules in the Thalamus in Schizophrenia and Bipolar Disorder. Neuropsychopharmacology, 2004, 29 (7), 1353-62. doi.org/10.1038/sj. npp.1300451
56. Clinton, S. M.; Haroutunian, V.; Meador-Woodruff, J. H., Upregulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia. J. Neurochem., 2006, 98 (4), 1114-25. doi.org/ 10.1111/j.1471-4159.2006.03954.x
57. Henson, M. A.; Roberts, A. C.; Salimi, K.; Vadlamudi, S.; Hamer, R. M.; Gilmore, J. H.; Jarskog, L. F.; Philpot, B. D. Developmental regulation of the NMDA receptor subunits, NR3A and NR1, in human prefrontal cortex. Cereb. Cortex, 2008, 18 (11), 2560-73. doi.org/10.1093/cercor/bhn017
58. Lyddon, R.; Navarrett, S.; Dracheva, S. Ionotropic glutamate receptor mRNA editing in the prefrontal cortex: no alterations in schizophrenia or bipolar disorder. J. Psychiatry Neurosci., 2012, 37 (4), 267-72. doi.org/10.1503/jpn.110107
59. Dracheva, S.; Byne, W.; Chin, B.; Haroutunian, V. Ionotropic glutamate receptor mRNA expression in the human thalamus: absence of change in schizophrenia. Brain Res., 2008, 1214, 23-34. doi.org/10.1016/j.brainres.2008.03.039
60. O'Connor, J. A.; Hemby, S. E. Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia. Schizophr. Res., 2007, 97 (1-3), 277-88. doi.org/10.1016/j.schres. 2007.09.022
61. O'Connor, J. A.; Muly, E. C.; Arnold, S. E.; Hemby, S. E. AMPA receptor subunit and splice variant expression in the DLPFC of schizophrenic subjects and rhesus monkeys chronically administered antipsychotic drugs. Schizophr. Res., 2007, 90 (1-3), 28-40. doi.org/10.1016/j.schres.2006.10.004
62. Harrison, P. J.; Lyon, L.; Sartorius, L. J.; Burnet, P. W.; Lane, T. A. The group II metabotropic glutamate receptor 3 (mGluR3, mGlu3, GRM3): expression, function and involvement in schizophrenia. J. Psychopharmacol., 2008, 22 (3), 308-22. doi.org/10.1177/ 0269881108089818
63. Gonzalez-Maeso, J.; Ang, R. L.; Yuen, T.; Chan, P.; Weisstaub, N. V.; Lopez-Gimenez, J. F.; Zhou, M.; Okawa, Y.; Callado, L. F.; Milligan, G.; Gingrich, J. A.; Filizola, M.; Meana, J. J.; Sealfon, S. C. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature, 2008, 452 (7183), 93-7. doi.org/10.1038/ nature06612
64. Ohnuma, T.; Augood, S. J.; Arai, H.; McKenna, P. J.; Emson, P. C. Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Brain Res Mol.Brain Res., 1998, 56 (1-2), 207-17. doi.org/10.1016/S0169- 328X(98)00063-1
65. Richardson-Burns, S. M.; Haroutunian, V.; Davis, K. L.; Watson, S. J.; Meador-Woodruff, J. H. Metabotropic glutamate receptor mRNA expression in the schizophrenic thalamus. Biol. Psychiatry, 2000, 47 (1), 22-8. doi.org/10.1016/S0006-3223(99)00207-3
66. Bullock, W. M.; Cardon, K.; Bustillo, J.; Roberts, R. C.; Perrone- Bizzozero, N. I. Altered expression of genes involved in GABAergic transmission and neuromodulation of granule cell activity in the cerebellum of schizophrenia patients. Am. J. Psychiatry, 2008, 165 (12), 1594-603. doi.org/10.1016/S0006- 3223(99)00207-3
67. Ghose, S.; Crook, J. M.; Bartus, C. L.; Sherman, T. G.; Herman, M. M.; Hyde, T. M.; Kleinman, J. E.; Akil, M. Metabotropic glutamate receptor 2 and 3 gene expression in the human prefrontal cortex and mesencephalon in schizophrenia. Int. J. Neurosci., 2008, 118 (11), 1609-27. doi.org/10.1080/00207450802330702
68. Crook, J. M.; Akil, M.; Law, B. C.; Hyde, T. M.; Kleinman, J. E. Comparative analysis of group II metabotropic glutamate receptor immunoreactivity in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects. Mol. Psychiatry, 2002, 7 (2), 157-64. doi.org/10.1038/ sj.mp.4000966
69. Gupta, D. S.; McCullumsmith, R. E.; Beneyto, M.; Haroutunian, V.; Davis, K. L.; Meador-Woodruff, J. H. Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia. Synapse, 2005, 57 (3), 123-31. doi.org/10.1002/ syn.20164
70. Ghose, S.; Gleason, K. A.; Potts, B. W.; Lewis-Amezcua, K.; Tamminga, C. A. Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: a mechanism for antipsychotic drug action? Am. J. Psychiatry, 2009, 166 (7), 812-20. doi.org/10. 1176/appi.ajp.2009.08091445
71. Corti, C.; Crepaldi, L.; Mion, S.; Roth, A. L.; Xuereb, J. H.; Ferraguti, F. Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia. Biol. Psychiatry, 2007, 62 (7), 747-55. doi.org/10.1016/j.biopsych.2006.12.005
72. Bondi, C.; Matthews, M.; Moghaddam, B. Glutamatergic animal models of schizophrenia. Curr. Pharm. Des., 2012, 18 (12), 1593- 604. doi.org/10.2174/138161212799958576
73. de Bartolomeis, A.; Fiore, G. Postsynaptic density scaffolding proteins at excitatory synapse and disorders of synaptic plasticity: implications for human behavior pathologies. Int. Rev. Neurobiol., 2004, 59, 221-54. doi.org/10.1016/S0074-7742(04)59009-8
74. Ohnuma, T.; Kato, H.; Arai, H.; Faull, R. L.; McKenna, P. J.; Emson, P. C. Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia. Neuroreport, 2000, 11 (14), 3133-7. doi.org/10.1097/00001756-200009280-00019
75. Dracheva, S.; Marras, S. A.; Elhakem, S. L.; Kramer, F. R.; Davis, K. L.; Haroutunian, V., N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia. Am. J. Psychiatry, 2001, 158 (9), 1400-10. doi.org/10.1176/appi.ajp.158.9.1400
76. Tsai, S. J.; Hong, C. J.; Cheng, C. Y.; Liao, D. L.; Liou, Y. J. Association study of polymorphisms in post-synaptic density protein 95 (PSD-95) with schizophrenia. J. Neural. Transm., 2007, 114 (4), 423-6. doi.org/10.1007/s00702-006-0587-2
77. Cheng, M. C.; Lu, C. L.; Luu, S. U.; Tsai, H. M.; Hsu, S. H.; Chen, T. T.; Chen, C. H. Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia. PLoS One, 2010, 5 (12), e15107. doi.org/10.1371/ journal.pone.0015107
78. Tomasetti, C.; Dell'Aversano, C.; Iasevoli, F.; Marmo, F.; de Bartolomeis, A. The acute and chronic effects of combined antipsychotic-mood stabilizing treatment on the expression of cortical and striatal postsynaptic density genes. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2011, 35 (1), 184-97. doi.org/ 10.1016/j.pnpbp.2010.10.025
79. de Bartolomeis, A.; Aloj, L.; Ambesi-Impiombato, A.; Bravi, D.; Caraco, C.; Muscettola, G.; Barone, P., Acute administration of antipsychotics modulates Homer striatal gene expression differentially. Brain Res. Mol. Brain Res., 2002, 98 (1-2), 124-9. doi.org/10.1016/S0169-328X(01)00327-8
80. Iasevoli, F.; Tomasetti, C.; Marmo, F.; Bravi, D.; Arnt, J.; de Bartolomeis, A. Divergent acute and chronic modulation of glutamatergic postsynaptic density genes expression by the antipsychotics haloperidol and sertindole. Psychopharmacology, (Berl) 2010, 212 (3), 329-44. doi.org/10.1007/s00213-010-1954-0
81. Iasevoli, F.; Ambesi-Impiombato, A.; Fiore, G.; Panariello, F.; Muscettola, G.; de Bartolomeis, A. Pattern of acute induction of Homer1a gene is preserved after chronic treatment with first- and second-generation antipsychotics: effect of short-term drug discontinuation and comparison with Homer1a-interacting genes. J. Psychopharmacol., 2011, 25 (7), 875-87. doi.org/10.1177/ 0269881109358199
82. Deng, C.; Pan, B.; Engel, M.; Huang, X. F. Neuregulin-1 signalling and antipsychotic treatment : Potential therapeutic targets in a schizophrenia candidate signalling pathway. Psychopharmacology (Berl), 2013, 226 (2), 201-15. doi.org/10.1007/s00213-013-3003-2
83. Hahn, C. G.; Wang, H. Y.; Cho, D. S.; Talbot, K.; Gur, R. E.; Berrettini, W. H.; Bakshi, K.; Kamins, J.; Borgmann-Winter, K. E.; Siegel, S. J.; Gallop, R. J.; Arnold, S. E. Altered neuregulin 1- erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med., 2006, 12 (7), 824-8. doi.org/10.1038/ nm1418
84. du Bois, T. M.; Newell, K. A.; Huang, X. F. Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life. Eur. Neuropsychopharmacol., 2011, 22,356- 63. doi.org/10.1016/j.euroneuro.2011.09.002
85. Brennand, K. J.; Simone, A.; Jou, J.; Gelboin-Burkhart, C.; Tran, N.; Sangar, S.; Li, Y.; Mu, Y.; Chen, G.; Yu, D.; McCarthy, S.; Sebat, J.; Gage, F. H., Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011, 473 (7346), 221-5. doi.org/10.1038/nature09915
86. Hung, A. Y.; Futai, K.; Sala, C.; Valtschanoff, J. G.; Ryu, J.; Woodworth, M. A.; Kidd, F. L.; Sung, C. C.; Miyakawa, T.; Bear, M. F.; Weinberg, R. J.; Sheng, M. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J. Neurosci., 2008, 28 (7), 1697-708. doi.org/ 10.1523/JNEUROSCI.3032-07.2008
87. Wohr, M.; Roullet, F. I.; Hung, A. Y.; Sheng, M.; Crawley, J. N. Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior. PLoS One, 2011, 6 (6), e20631. doi.org/10.1371/journal.pone.0020631
88. Lennertz, L.; Wagner, M.; Wolwer, W.; Schuhmacher, A.; Frommann, I.; Berning, J.; Schulze-Rauschenbach, S.; Landsberg, M. W.; Steinbrecher, A.; Alexander, M.; Franke, P. E.; Pukrop, R.; Ruhrmann, S.; Bechdolf, A.; Gaebel, W.; Klosterkotter, J.; Hafner, H.; Maier, W.; Mossner, R. A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis. Eur. Arch. Psychiatry Clin. Neurosci., 2012, 262 (2), 117-24. doi.org/10.1007/s00406-011- 0233-3
89. Delahaye, A.; Toutain, A.; Aboura, A.; Dupont, C.; Tabet, A. C.; Benzacken, B.; Elion, J.; Verloes, A.; Pipiras, E.; Drunat, S., Chromosome 22q13.3 deletion syndrome with a de novo interstitial 22q13.3 cryptic deletion disrupting SHANK3. Eur. J. Med. Genet., 2009, 52 (5), 328-32. doi.org/10.1016/j.ejmg.2009.05.004
90. Liu, J.; Ulloa, A.; Perrone-Bizzozero, N.; Yeo, R.; Chen, J.; Calhoun, V. D., A pilot study on collective effects of 22q13.31 deletions on gray matter concentration in schizophrenia. PLoS One, 2012, 7 (12), e52865. doi.org/10.1371/journal.pone.0052865
91. Gauthier, J.; Champagne, N.; Lafreniere, R. G.; Xiong, L.; Spiegelman, D.; Brustein, E.; Lapointe, M.; Peng, H.; Cote, M.; Noreau, A.; Hamdan, F. F.; Addington, A. M.; Rapoport, J. L.; Delisi, L. E.; Krebs, M. O.; Joober, R.; Fathalli, F.; Mouaffak, F.; Haghighi, A. P.; Neri, C.; Dube, M. P.; Samuels, M. E.; Marineau, C.; Stone, E. A.; Awadalla, P.; Barker, P. A.; Carbonetto, S.; Drapeau, P.; Rouleau, G. A.; Team, S. D. De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proc. Natl. Acad. Sci. U. S. A., 2010, 107 (17), 7863-8. doi.org/10.1073/pnas.0906232107
92. Hayashi, M. K.; Tang, C.; Verpelli, C.; Narayanan, R.; Stearns, M. H.; Xu, R. M.; Li, H.; Sala, C.; Hayashi, Y. The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell 2009, 137 (1), 159-71. doi.org/10.1016/j.cell.2009. 01.050
93. Sala, C.; Roussignol, G.; Meldolesi, J.; Fagni, L. Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons. J. Neurosci., 2005, 25 (18), 4587-92. doi.org/10.1073/pnas.0906232107
94. de Bartolomeis, A.; Tomasetti, C. Calcium-dependent networks in dopamine-glutamate interaction: the role of postsynaptic scaffolding proteins. Mol. Neurobiol., 2012, 46 (2), 275-96. doi.org/10.1007/ s12035-012-8293-6
95. Bertaso, F.; Roussignol, G.; Worley, P.; Bockaert, J.; Fagni, L.; Ango, F. Homer1a-dependent crosstalk between NMDA and metabotropic glutamate receptors in mouse neurons. PLoS One, 2010, 5 (3), e9755. doi.org/10.1371/journal.pone.0009755
96. Carlisle, H. J.; Kennedy, M. B. Spine architecture and synaptic plasticity. Trends Neurosci., 2005, 28 (4), 182-7. doi.org/10.1016/ j.tins.2005.01.008
97. Peca, J.; Feliciano, C.; Ting, J. T.; Wang, W.; Wells, M. F.; Venkatraman, T. N.; Lascola, C. D.; Fu, Z.; Feng, G., Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 2011, 472 (7344), 437-42. doi.org/10.1038/nature09965
98. Roussignol, G.; Ango, F.; Romorini, S.; Tu, J. C.; Sala, C.; Worley, P. F.; Bockaert, J.; Fagni, L. Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. J. Neurosci., 2005, 25 (14), 3560-70. doi.org/10.1523/JNEUROSCI. 4354-04.2005
99. Kammermeier, P. J. Endogenous homer proteins regulate metabotropic glutamate receptor signaling in neurons. J Neurosci 2008, 28 (34), 8560-7. doi.org/10.1523/JNEUROSCI.1830-08.2008
100. de Bartolomeis, A.; Buonaguro, E. F.; Iasevoli, F. Serotoninglutamate and serotonin-dopamine reciprocal interactions as putative molecular targets for novel antipsychotic treatments: from receptor heterodimers to postsynaptic scaffolding and effector proteins. Psychopharmacology (Berl) 2013, 225 (1), 1-19. doi.org/ 10.1007/s00213-012-2921-8
101. de Bartolomeis, A.; Iasevoli, F. The Homer family and the signal transduction system at glutamatergic postsynaptic density: potential role in behavior and pharmacotherapy. Psychopharmacol. Bull., 2003, 37 (3), 51-83. PMID: 14608240
102. Shiraishi-Yamaguchi, Y.; Furuichi, T. The Homer family proteins. Genome Biol., 2007, 8 (2), 206. DOI: 10.1186/gb-2007-8-2-206
103. Iasevoli, F.; Polese, D.; Ambesi-Impiombato, A.; Muscettola, G.; de Bartolomeis, A., Ketamine-related expression of glutamatergic postsynaptic density genes: possible implications in psychosis. Neurosci. Lett., 2007, 416 (1), 1-5. doi.org/10.1016/j.neulet.2007. 01.041
104. Norton, N.; Williams, H. J.; Williams, N. M.; Spurlock, G.; Zammit, S.; Jones, G.; Jones, S.; Owen, R.; O'Donovan, M. C.; Owen, M. J., Mutation screening of the Homer gene family and association analysis in schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet., 2003, 120B (1), 18-21. doi.org/10.1002/ ajmg.b.20032
105. De Luca, V.; Annesi, G.; De Marco, E. V.; de Bartolomeis, A.; Nicoletti, G.; Pugliese, P.; Muscettola, G.; Barone, P.; Quattrone, A. HOMER1 promoter analysis in Parkinson's disease: association study with psychotic symptoms. Neuropsychobiology, 2009, 59 (4), 239-45. doi.org/10.1159/000230689
106. Spellmann, I.; Rujescu, D.; Musil, R.; Mayr, A.; Giegling, I.; Genius, J.; Zill, P.; Dehning, S.; Opgen-Rhein, M.; Cerovecki, A.; Hartmann, A. M.; Schafer, M.; Bondy, B.; Muller, N.; Moller, H. J.; Riedel, M. Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients. J. Psychiatr. Res., 2011, 45 (2), 234-41. doi.org/10.1016/ j.jpsychires.2010.06.004
107. Iasevoli, F.; Fiore, G.; Cicale, M.; Muscettola, G.; de Bartolomeis, A. Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions. Psychiatry Res., 2010, 177 (1-2), 255-60. doi.org/10.1016/j.psychres.2010.02.009
108. Sala, C.; Piech, V.; Wilson, N. R.; Passafaro, M.; Liu, G.; Sheng, M. Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron, 2001, 31 (1), 115-30. doi.org/10. 1016/S0896-6273(01)00339-7
109. Sala, C.; Futai, K.; Yamamoto, K.; Worley, P. F.; Hayashi, Y.; Sheng, M. Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a. J. Neurosci., 2003, 23 (15), 6327-37. PMID: 12867517
110. Celikel, T.; Marx, V.; Freudenberg, F.; Zivkovic, A.; Resnik, E.; Hasan, M. T.; Licznerski, P.; Osten, P.; Rozov, A.; Seeburg, P. H.; Schwarz, M. K. Select overexpression of homer1a in dorsal hippocampus impairs spatial working memory. Front. Neurosci., 2007, 1 (1), 97-110. doi.org/10.3389/neuro.01.1.1.007.2007
111. Ueta, Y.; Yamamoto, R.; Sugiura, S.; Inokuchi, K.; Kato, N. Homer 1a suppresses neocortex long-term depression in a cortical layer-specific manner. J. Neurophysiol., 2008, 99 (2), 950-7. doi.org/10.1152/jn.01101.2007
112. Gerstein, H.; O'Riordan, K.; Osting, S.; Schwarz, M.; Burger, C. Rescue of synaptic plasticity and spatial learning deficits in the hippocampus of Homer1 knockout mice by recombinant Adenoassociated viral gene delivery of Homer1c. Neurobiol. Learn Mem., 2012, 97 (1), 17-29. doi.org/10.1016/j.nlm.2011.08.009
113. Szumlinski, K. K.; Lominac, K. D.; Kleschen, M. J.; Oleson, E. B.; Dehoff, M. H.; Schwarz, M. K.; Seeburg, P. H.; Worley, P. F.; Kalivas, P. W. Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia. Genes Brain Behav., 2005, 4 (5), 273-88. doi.org/10.1111/j.1601-183X. 2005.00120.x
114. Jaubert, P. J.; Golub, M. S.; Lo, Y. Y.; Germann, S. L.; Dehoff, M. H.; Worley, P. F.; Kang, S. H.; Schwarz, M. K.; Seeburg, P. H.; Berman, R. F. Complex, multimodal behavioral profile of the Homer1 knockout mouse. Genes Brain Behav., 2007, 6 (2), 141-54. doi.org/10.1111/j.1601-183X.2006.00240.x
115. Lominac, K. D.; Oleson, E. B.; Pava, M.; Klugmann, M.; Schwarz, M. K.; Seeburg, P. H.; During, M. J.; Worley, P. F.; Kalivas, P. W.; Szumlinski, K. K., Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function. J. Neurosci., 2005, 25 (50), 11586-94. doi.org/10.1523/JNEUROSCI.3764-05. 2005
116. Tappe, A.; Kuner, R., Regulation of motor performance and striatal function by synaptic scaffolding proteins of the Homer1 family. Proc. Natl. Acad. Sci. U. S. A., 2006, 103 (3), 774-9. doi.org/ 10.1073/pnas.0505900103
117. Iasevoli, F.; Cicale, M.; Abbott, L. C.; de Bartolomeis, A., Striatal expression of Homer1a is affected by genotype but not dystonic phenotype of tottering mice: a model of spontaneously occurring motor disturbances. Neurosci. Lett., 2011, 503 (3), 176-80. doi.org/ 10.1016/j.neulet.2011.08.025
118. Cochran, S. M.; Fujimura, M.; Morris, B. J.; Pratt, J. A., Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain. Synapse, 2002, 46 (3), 206-14. doi.org/10.1002/syn.10126
119. Molteni, R.; Pasini, M.; Moraschi, S.; Gennarelli, M.; Drago, F.; Racagni, G.; Riva, M. A. Reduced activation of intracellular signaling pathways in rat prefrontal cortex after chronic phencyclidine administration. Pharmacol. Res., 2008, 57 (4), 296- 302. doi.org/10.1016/j.phrs.2008.02.007
120. Mouri, A.; Noda, Y.; Noda, A.; Nakamura, T.; Tokura, T.; Yura, Y.; Nitta, A.; Furukawa, H.; Nabeshima, T., Involvement of a dysfunctional dopamine-D1/N-methyl-d-aspartate-NR1 and Ca2+/ calmodulin-dependent protein kinase II pathway in the impairment of latent learning in a model of schizophrenia induced by phencyclidine. Mol. Pharmacol., 2007, 71 (6), 1598-609. doi.org/ 10.1124/mol.106.032961
121. Yamasaki, N.; Maekawa, M.; Kobayashi, K.; Kajii, Y.; Maeda, J.; Soma, M.; Takao, K.; Tanda, K.; Ohira, K.; Toyama, K.; Kanzaki, K.; Fukunaga, K.; Sudo, Y.; Ichinose, H.; Ikeda, M.; Iwata, N.; Ozaki, N.; Suzuki, H.; Higuchi, M.; Suhara, T.; Yuasa, S.; Miyakawa, T. Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol. Brain, 2008, 1, 6. doi.org/10.1186/1756-6606-1-6
122. Novak, G.; Seeman, P.Hyperactive mice show elevated D2(High) receptors, a model for schizophrenia: Calcium/calmodulindependent kinase II alpha knockouts. Synapse, 2010, 64 (10), 794- 800. doi: 10.1002/syn.20786
123. Carlisle, H. J.; Luong, T. N.; Medina-Marino, A.; Schenker, L.; Khorosheva, E.; Indersmitten, T.; Gunapala, K. M.; Steele, A. D.; O'Dell, T. J.; Patterson, P. H.; Kennedy, M. B. Deletion of densin- 180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction. J. Neurosci., 2011, 31 (45), 16194-207. doi.org/10.1523/ JNEUROSCI.5877-10.2011
124. Albert, K. A.; Hemmings, H. C., Jr.; Adamo, A. I.; Potkin, S. G.; Akbarian, S.; Sandman, C. A.; Cotman, C. W.; Bunney, W. E., Jr.; Greengard, P. Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia. Arch. Gen. Psychiatry, 2002, 59 (8), 705-12. doi.org/10.1001/archpsyc.59.8.705
125. Novak, G.; Seeman, P.; Tallerico, T. Increased expression of calcium/calmodulin-dependent protein kinase IIbeta in frontal cortex in schizophrenia and depression. Synapse, 2006, 59 (1), 61- 8. doi.org/10.1002/syn.20211
126. Penzes, P.; Johnson, R. C.; Alam, M. R.; Kambampati, V.; Mains, R. E.; Eipper, B. A. An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction. J. Biol. Chem., 2000, 275 (9), 6395-403. doi.org/10.1074/ jbc.275.9.6395
127. Penzes, P.; Beeser, A.; Chernoff, J.; Schiller, M. R.; Eipper, B. A.; Mains, R. E.; Huganir, R. L. Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron, 2003, 37 (2), 263-74. doi.org/ 10.1016/S0896-6273(02)01168-6
128. Penzes, P.; Cahill, M. E.; Jones, K. A.; VanLeeuwen, J. E.; Woolfrey, K. M. Dendritic spine pathology in neuropsychiatric disorders. Nat. Neurosci., 2011, 14 (3), 285-93. doi.org/10.1038/ nn.2741
129. Penzes, P.; Johnson, R. C.; Sattler, R.; Zhang, X.; Huganir, R. L.; Kambampati, V.; Mains, R. E.; Eipper, B. A. The neuronal Rho- GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron, 2001, 29 (1), 229-42. doi.org/10.1016/S0896-6273(01)00193-3
130. Xie, Z.; Srivastava, D. P.; Photowala, H.; Kai, L.; Cahill, M. E.; Woolfrey, K. M.; Shum, C. Y.; Surmeier, D. J.; Penzes, P. Kalirin- 7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron, 2007, 56 (4), 640-56. doi.org/10.1016/ j.neuron.2007.10.005
131. Ma, X. M.; Wang, Y.; Ferraro, F.; Mains, R. E.; Eipper, B. A., Kalirin-7 is an essential component of both shaft and spine excitatory synapses in hippocampal interneurons. J. Neurosci., 2008, 28 (3), 711-24. doi.org/10.1523/JNEUROSCI.5283-07.2008
132. Cahill, M. E.; Xie, Z.; Day, M.; Photowala, H.; Barbolina, M. V.; Miller, C. A.; Weiss, C.; Radulovic, J.; Sweatt, J. D.; Disterhoft, J. F.; Surmeier, D. J.; Penzes, P. Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes. Proc Natl. Acad. Sci .U. S. A., 2009, 106 (31), 13058-63. doi.org/ 10.1073/pnas.0904636106
133. Ma, X. M.; Kiraly, D. D.; Gaier, E. D.; Wang, Y.; Kim, E. J.; Levine, E. S.; Eipper, B. A.; Mains, R. E. Kalirin-7 is required for synaptic structure and function. J. Neurosci., 2008, 28 (47), 12368- 82. doi.org/10.1523/JNEUROSCI.4269-08.2008
134. Kiraly, D. D.; Lemtiri-Chlieh, F.; Levine, E. S.; Mains, R. E.; Eipper, B. A. Kalirin binds the NR2B subunit of the NMDA receptor, altering its synaptic localization and function. J. Neurosci., 2011, 31 (35), 12554-65. doi.org/10.1523/JNEUROSCI. 3143-11.2011
135. Hayashi-Takagi, A.; Takaki, M.; Graziane, N.; Seshadri, S.; Murdoch, H.; Dunlop, A. J.; Makino, Y.; Seshadri, A. J.; Ishizuka, K.; Srivastava, D. P.; Xie, Z.; Baraban, J. M.; Houslay, M. D.; Tomoda, T.; Brandon, N. J.; Kamiya, A.; Yan, Z.; Penzes, P.; Sawa, A., Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat. Neurosci., 2010, 13 (3), 327-32. doi.org/10.1038/nn.2487
136. Kushima, I.; Nakamura, Y.; Aleksic, B.; Ikeda, M.; Ito, Y.; Shiino, T.; Okochi, T.; Fukuo, Y.; Ujike, H.; Suzuki, M.; Inada, T.; Hashimoto, R.; Takeda, M.; Kaibuchi, K.; Iwata, N.; Ozaki, N., Resequencing and Association Analysis of the KALRN and EPHB1 Genes And Their Contribution to Schizophrenia Susceptibility. Schizophr. Bull., 2010, 38(3), 552-60. doi: 10.1093/ schbul/sbq118
137. Deo, A. J.; Cahill, M. E.; Li, S.; Goldszer, I.; Henteleff, R.; Vanleeuwen, J. E.; Rafalovich, I.; Gao, R.; Stachowski, E. K.; Sampson, A. R.; Lewis, D. A.; Penzes, P.; Sweet, R. A. Increased expression of Kalirin-9 in the auditory cortex of schizophrenia subjects: Its role in dendritic pathology. Neurobiol. Dis., 2012, 45 (2), 796-803. doi.org/10.1016/j.nbd.2011.11.003
138. Hiraoka, S.; Kajii, Y.; Kuroda, Y.; Umino, A.; Nishikawa, T. The development- and phencyclidine-regulated induction of synapse-associated protein-97 gene in the rat neocortex. Eur. Neuropsychopharmacol., 2010, 20 (3), 176-86. doi.org/10.1016/ j.euroneuro.2009.08.007
139. Toyooka, K.; Iritani, S.; Makifuchi, T.; Shirakawa, O.; Kitamura, N.; Maeda, K.; Nakamura, R.; Niizato, K.; Watanabe, M.; Kakita, A.; Takahashi, H.; Someya, T.; Nawa, H., Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia. J. Neurochem., 2002, 83 (4), 797-806. doi.org/10.1046/j.1471-4159.2002.01181.x
140. Hammond, J. C.; McCullumsmith, R. E.; Funk, A. J.; Haroutunian, V.; Meador-Woodruff, J. H. Evidence for abnormal forward trafficking of AMPA receptors in frontal cortex of elderly patients with schizophrenia. Neuropsychopharmacology, 2010, 35 (10), 2110-9. doi.org/10.1038/npp.2010.87
141. Sato, J.; Shimazu, D.; Yamamoto, N.; Nishikawa, T. An association analysis of synapse-associated protein 97 (SAP97) gene in schizophrenia. J. Neural Transm., 2008, 115 (9), 1355-65. doi.org/10.1007/s00702-008-0085-9
142. Uezato, A.; Kimura-Sato, J.; Yamamoto, N.; Iijima, Y.; Kunugi, H.; Nishikawa, T. Further evidence for a male-selective genetic association of synapse-associated protein 97 (SAP97) gene with schizophrenia. Behav. Brain Funct., 2012, 8 (1), 2. doi.org/10. 1186/1744-9081-8-2
143. Kristiansen, L. V.; Beneyto, M.; Haroutunian, V.; Meador- Woodruff, J. H. Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia. Mol. Psychiatry, 2006, 11 (8), 737-47, 705. doi.org/ 10.1038/sj.mp.4001844
144. Kristiansen, L. V.; Meador-Woodruff, J. H. Abnormal striatal expression of transcripts encoding NMDA interacting PSD proteins in schizophrenia, bipolar disorder and major depression. Schizophr. Res., 2005, 78 (1), 87-93. doi.org/10.1016/j.schres.2005.06.012
145. Mueller, H. T.; Haroutunian, V.; Davis, K. L.; Meador-Woodruff, J. H. Expression of the ionotropic glutamate receptor subunits and NMDA receptor-associated intracellular proteins in the substantia nigra in schizophrenia. Brain Res. Mol. Brain Res., 2004, 121 (1- 2), 60-9. doi.org/10.1016/j.molbrainres.2003.11.004
146. Fujii, K.; Maeda, K.; Hikida, T.; Mustafa, A. K.; Balkissoon, R.; Xia, J.; Yamada, T.; Ozeki, Y.; Kawahara, R.; Okawa, M.; Huganir, R. L.; Ujike, H.; Snyder, S. H.; Sawa, A., Serine racemase binds to PICK1: potential relevance to schizophrenia. Mol Psychiatry 2006, 11 (2), 150-7. doi.org/10.1038/sj.mp.4001776
147. Hong, C. J.; Liao, D. L.; Shih, H. L.; Tsai, S. J., Association study of PICK1 rs3952 polymorphism and schizophrenia. Neuroreport, 2004, 15 (12), 1965-7. doi.org/10.1097/00001756-200408260- 00026
148. Dev, K. K.; Henley, J. M. The schizophrenic faces of PICK1. Trends Pharmacol. Sci., 2006, 27 (11), 574-9. doi.org/10.1016/ j.tips.2006.09.007
149. Ishiguro, H.; Koga, M.; Horiuchi, Y.; Inada, T.; Iwata, N.; Ozaki, N.; Ujike, H.; Muratake, T.; Someya, T.; Arinami, T., PICK1 is not a susceptibility gene for schizophrenia in a Japanese population: association study in a large case-control population. Neurosci Res 2007, 58 (2), 145-8. doi.org/10.1016/j.neures.2007.02.008
150. de Bartolomeis, A.; Fiore, G.; Iasevoli, F. Dopamine-glutamate interaction and antipsychotics mechanism of action: implication for new pharmacological strategies in psychosis. Curr. Pharm. Des. 2005, 11 (27), 3561-94. doi.org/10.2174/138161205774414538
151. Seeman, P. Glutamate and dopamine components in schizophrenia. J Psychiatry Neurosci., 2009, 34 (2), 143-9. PMID: 19270765
152. Hallett, P. J.; Spoelgen, R.; Hyman, B. T.; Standaert, D. G.; Dunah, A. W. Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking. J. Neurosci., 2006, 26 (17), 4690-700. doi.org/10.1523/JNEUROSCI. 0792-06.2006
153. Li, Y. C.; Liu, G.; Hu, J. L.; Gao, W. J.; Huang, Y. Q. Dopamine D(1) receptor-mediated enhancement of NMDA receptor trafficking requires rapid PKC-dependent synaptic insertion in the prefrontal neurons. J. Neurochem., 2010, 114 (1), 62-73. doi: 10.1111/j.1471- 4159.2010.06720.x
154. Scott, L.; Kruse, M. S.; Forssberg, H.; Brismar, H.; Greengard, P.; Aperia, A. Selective up-regulation of dopamine D1 receptors in dendritic spines by NMDA receptor activation. Proc. Natl. Acad. Sci. U. S. A. 2002, 99 (3), 1661-4. doi.org/10.1073/pnas.032654599
155. Lee, F. J.; Xue, S.; Pei, L.; Vukusic, B.; Chery, N.; Wang, Y.; Wang, Y. T.; Niznik, H. B.; Yu, X. M.; Liu, F. Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell, 2002, 111 (2), 219-30. doi.org/10.1016/S0092-8674(02)00962-5
156. Pei, L.; Lee, F. J.; Moszczynska, A.; Vukusic, B.; Liu, F., Regulation of dopamine D1 receptor function by physical interaction with the NMDA receptors. J. Neurosci., 2004, 24 (5), 1149-58. doi.org/10.1523/JNEUROSCI.3922-03.2004
157. Nai, Q.; Li, S.; Wang, S. H.; Liu, J.; Lee, F. J.; Frankland, P. W.; Liu, F. Uncoupling the D1-N-methyl-D-aspartate (NMDA) receptor complex promotes NMDA-dependent long-term potentiation and working memory. Biol. Psychiatry, 2010, 67 (3), 246-54. doi.org/ 10.1016/j.biopsych.2009.08.011
158. Zhang, J.; Xu, T. X.; Hallett, P. J.; Watanabe, M.; Grant, S. G.; Isacson, O.; Yao, W. D., PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complex. J. Neurosci., 2009, 29 (9), 2948-60. doi.org/10.1523/JNEUROSCI. 4424-08.2009
159. Zhang, J.; Vinuela, A.; Neely, M. H.; Hallett, P. J.; Grant, S. G.; Miller, G. M.; Isacson, O.; Caron, M. G.; Yao, W. D. Inhibition of the dopamine D1 receptor signaling by PSD-95. J. Biol. Chem. 2007, 282 (21), 15778-89. doi.org/10.1074/jbc.M611485200
160. Brown, A. M.; Deutch, A. Y.; Colbran, R. J. Dopamine depletion alters phosphorylation of striatal proteins in a model of Parkinsonism. Eur. J. Neurosci., 2005, 22 (1), 247-56. doi.org/ 10.1111/j.1460-9568.2005.04190.x
161. Gu, Z.; Jiang, Q.; Yuen, E. Y.; Yan, Z. Activation of dopamine D4 receptors induces synaptic translocation of Ca2+/calmodulindependent protein kinase II in cultured prefrontal cortical neurons. Mol. Pharmacol., 2006, 69 (3), 813-22. PMID:16365279
162. Li, Y. C.; Xi, D.; Roman, J.; Huang, Y. Q.; Gao, W. J. Activation of glycogen synthase kinase-3 beta is required for hyperdopamine and D2 receptor-mediated inhibition of synaptic NMDA receptor function in the rat prefrontal cortex. J. Neurosci., 2009, 29 (49), 15551-63. doi.org/10.1523/JNEUROSCI.3336-09.2009
163. de Bartolomeis, A.; Sarappa, C.; Magara, S.; Iasevoli, F. Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia. Eur. J. Pharmacol., 2012, 682 (1-3), 1-11. Eur. J. Pharmacol., 2012, 682 (1-3), 1-11. doi.org/10.1016/j.ejphar.2012.02.033
164. Critchlow, H. M.; Maycox, P. R.; Skepper, J. N.; Krylova, O. Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons. Mol. Cell Neurosci., 2006, 32 (4), 356-65. doi.org/10.1016/j.mcn.2006. 05.007
165. Jardemark, K. E.; Konradsson, A.; Schilstrom, B.; Marcus, M. M.; Svensson, T. H. Differential effects of topiramate on prefrontal glutamatergic transmission when combined with raclopride or clozapine. Synapse, 2009, 63 (10), 913-20. doi.org/10.1002/syn. 20674
166. Pratt, J. A.; Winchester, C.; Egerton, A.; Cochran, S. M.; Morris, B. J. Modelling prefrontal cortex deficits in schizophrenia: implications for treatment. Br. J. Pharmacol., 2008, 153 Suppl 1, S465-70. doi.org/10.1038/bjp.2008.24
167. Neill, J. C.; Barnes, S.; Cook, S.; Grayson, B.; Idris, N. F.; McLean, S. L.; Snigdha, S.; Rajagopal, L.; Harte, M. K. Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacol. Ther., 2010, 128 (3), 419-32. doi.org/10.1016/j.pharmthera.2010. 07.004
168. Purkayastha, S.; Ford, J.; Kanjilal, B.; Diallo, S.; Del Rosario Inigo, J.; Neuwirth, L.; El Idrissi, A.; Ahmed, Z.; Wieraszko, A.; Azmitia, E. C.; Banerjee, P., Clozapine functions through the prefrontal cortex serotonin 1A receptor to heighten neuronal activity via calmodulin kinase II-NMDA receptor interactions. J. Neurochem., 2012, 120 (3), 396-407. doi.org/10.1111/j.1471- 4159.2011.07565.x
169. Abbas, A. I.; Yadav, P. N.; Yao, W. D.; Arbuckle, M. I.; Grant, S. G.; Caron, M. G.; Roth, B. L. PSD-95 is essential for hallucinogen and atypical antipsychotic drug actions at serotonin receptors. J. Neurosci., 2009, 29 (22), 7124-36. doi.org/10.1523/JNEUROSCI. 1090-09.2009
170. Menniti, F. S.; Faraci, W. S.; Schmidt, C. J., Phosphodiesterases in the CNS: targets for drug development. Nat. Rev. Drug Discov., 2006, 5 (8), 660-70. doi.org/10.1038/nrd2058
171. Grauer, S. M.; Pulito, V. L.; Navarra, R. L.; Kelly, M. P.; Kelley, C.; Graf, R.; Langen, B.; Logue, S.; Brennan, J.; Jiang, L.; Charych, E.; Egerland, U.; Liu, F.; Marquis, K. L.; Malamas, M.; Hage, T.; Comery, T. A.; Brandon, N. J. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J. Pharm. Exp. Ther., 2009, 331 (2), 574-90. doi.org/10.1124/jpet.109.155994
172. Kanes, S. J.; Tokarczyk, J.; Siegel, S. J.; Bilker, W.; Abel, T.; Kelly, M. P. Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity. Neuroscience, 2007, 144 (1), 239-46. doi.org/10.1016/j.neuroscience.2006.09.026
173. Kuroiwa, M.; Snyder, G. L.; Shuto, T.; Fukuda, A.; Yanagawa, Y.; Benavides, D. R.; Nairn, A. C.; Bibb, J. A.; Greengard, P.; Nishi, A. Phosphodiesterase 4 inhibition enhances the dopamine D1 receptor/PKA/DARPP-32 signaling cascade in frontal cortex. Psychopharmacology (Berl) 2012, 219 (4), 1065-79. doi.org/ 10.1007/s00213-011-2436-8
174. Iasevoli, F.; Tomasetti, C.; Ambesi-Impiombato, A.; Muscettola, G.; de Bartolomeis, A. Dopamine receptor subtypes contribution to Homer1a induction: insights into antipsychotic molecular action. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33 (5), 813- 21. doi.org/10.1016/j.pnpbp.2009.02.009
175. Tomasetti, C.; Dell'Aversano, C.; Iasevoli, F.; de Bartolomeis, A. Homer splice variants modulation within cortico-subcortical regions by dopamine D2 antagonists, a partial agonist, and an indirect agonist: implication for glutamatergic postsynaptic density in antipsychotics action. Neuroscience, 2007, 150 (1), 144-58. doi.org/10.1016/j.neuroscience.2007.08.022
176. Ambesi-Impiombato, A.; Panariello, F.; Dell'aversano, C.; Tomasetti, C.; Muscettola, G.; de Bartolomeis, A. Differential expression of Homer 1 gene by acute and chronic administration of antipsychotics and dopamine transporter inhibitors in the rat forebrain. Synapse, 2007, 61 (6), 429-39. doi.org/10.1002/syn. 20385
177. de Bartolomeis, A.; Marmo, F.; Filomena Buonaguro, E.; Rossi, R.; Tomasetti, C.; Iasevoli, F., Imaging brain gene expression profiles by antipsychotics: Region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol. Eur. Neuropsychopharmacol. 2013. doi.org/10.1016/j.euroneuro.2012. 11.014
178. Zhang, G. C.; Mao, L. M.; Liu, X. Y.; Parelkar, N. K.; Arora, A.; Yang, L.; Hains, M.; Fibuch, E. E.; Wang, J. Q. In vivo regulation of Homer1a expression in the striatum by cocaine. Mol. Pharmacol. 2007, 71 (4), 1148-58. doi.org/10.1124/mol.106. 028399
179. Ghasemzadeh, M. B.; Windham, L. K.; Lake, R. W.; Acker, C. J.; Kalivas, P. W. Cocaine activates Homer1 immediate early gene transcription in the mesocorticolimbic circuit: differential regulation by dopamine and glutamate signaling. Synapse, 2009, 63 (1), 42-53. doi.org/10.1002/syn.20577
180. Yano, M.; Beverley, J. A.; Steiner, H., Inhibition of methylphenidate-induced gene expression in the striatum by local blockade of D1 dopamine receptors: interhemispheric effects. Neuroscience, 2006, 140 (2), 699-709. doi.org/10.1016/j. neuroscience.2006.02.017
181. Yamada, H.; Kuroki, T.; Nakahara, T.; Hashimoto, K.; Tsutsumi, T.; Hirano, M.; Maeda, H. The dopamine D1 receptor agonist, but not the D2 receptor agonist, induces gene expression of Homer 1a in rat striatum and nucleus accumbens. Brain Res., 2007, 1131 (1), 88-96. doi.org/10.1016/j.brainres.2006.11.011
182. Westerink, B. H.; Kawahara, Y.; De Boer, P.; Geels, C.; De Vries, J. B.; Wikstrom, H. V.; Van Kalkeren, A.; Van Vliet, B.; Kruse, C. G.; Long, S. K. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum. Eur. J. Pharmacol., 2001, 412 (2), 127-38. doi.org/ 10.1016/S0014-2999(00)00935-3
183. Heres, S.; Davis, J.; Maino, K.; Jetzinger, E.; Kissling, W.; Leucht, S. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of headto- head comparison studies of second-generation antipsychotics. Am. J. Psychiatry, 2006, 163 (2), 185-94. doi.org/10.1176/appi. ajp.163.2.185
184. Bertolino, A.; Blasi, G. The genetics of schizophrenia. Neuroscience, 2009, 164 (1), 288-99. doi.org/10.1016/j.neuroscience. 2009.04.038
185. Papaleo, F.; Lipska, B. K.; Weinberger, D. R. Mouse models of genetic effects on cognition: relevance to schizophrenia. Neuropharmacology, 2012, 62 (3), 1204-20. doi.org/10.1016/ j.neuropharm.2011.04.025
186. Thomases, D. R.; Cass, D. K.; Tseng, K. Y., Periadolescent exposure to the NMDA receptor antagonist MK-801 impairs the functional maturation of local GABAergic circuits in the adult prefrontal cortex. J. Neurosci., 2013, 33 (1), 26-34. doi.org/ 10.1523/JNEUROSCI.4147-12.2013
187. Rujescu, D.; Genius, J.; Benninghoff, J.; Giegling, I. Current progress in the genetic research of schizophrenia: relevance for drug discovery? Curr. Pharm. Biotechnol., 2012, 13 (8), 1614-21. doi.org/10.2174/138920112800784754
188. Moreau, A. W.; Kullmann, D. M. NMDA receptor-dependent function and plasticity in inhibitory circuits. Neuropharmacology, 2013, 74, 23-31. doi.org/10.1016/j.neuropharm.2013.03.004
189. Wiescholleck, V.; Manahan-Vaughan, D. Long-lasting changes in hippocampal synaptic plasticity and cognition in an animal model of NMDA receptor dysfunction in psychosis. Neuropharmacology, 2013, 74, 48-58. doi.org/10.1016/j.neuropharm.2013.01.001
190. Cook, D. J.; Teves, L.; Tymianski, M. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature, 2012, 483 (7388), 213-7. doi.org/10.1038/nature10841
191. Bach, A.; Clausen, B. H.; Moller, M.; Vestergaard, B.; Chi, C. N.; Round, A.; Sorensen, P. L.; Nissen, K. B.; Kastrup, J. S.; Gajhede, M.; Jemth, P.; Kristensen, A. S.; Lundstrom, P.; Lambertsen, K. L.; Stromgaard, K., A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proc. Natl. Acad. Sci. U. S. A., 2012, 109 (9), 3317- 22. doi.org/10.1073/pnas.1113761109
192. Zhang, L.; Torgerson, T. R.; Liu, X. Y.; Timmons, S.; Colosia, A. D.; Hawiger, J.; Tam, J. P. Preparation of functionally active cellpermeable peptides by single-step ligation of two peptide modules. Proc. Natl. Acad. Sci. U. S. A., 1998, 95 (16), 9184-9. doi.org/ 10.1073/pnas.95.16.9184
193. Joliot, A.; Prochiantz, A. Transduction peptides: from technology to physiology. Nat. Cell Biol., 2004, 6 (3), 189-96. doi.org/10. 1038/ncb0304-189
194. Noguchi, H.; Matsushita, M.; Okitsu, T.; Moriwaki, A.; Tomizawa, K.; Kang, S.; Li, S. T.; Kobayashi, N.; Matsumoto, S.; Tanaka, K.; Tanaka, N.; Matsui, H. A new cell-permeable peptide allows successful allogeneic islet transplantation in mice. Nat. Med., 2004, 10 (3), 305-9. doi.org/10.1038/nm994
195. Mamidipudi, V.; Dhillon, N. K.; Parman, T.; Miller, L. D.; Lee, K. C.; Cartwright, C. A., RACK1 inhibits colonic cell growth by regulating Src activity at cell cycle checkpoints. Oncogene, 2007, 26 (20), 2914-24. doi.org/10.1038/sj.onc.1210091
196. Borsello, T.; Clarke, P. G.; Hirt, L.; Vercelli, A.; Repici, M.; Schorderet, D. F.; Bogousslavsky, J.; Bonny, C. A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat. Med., 2003, 9 (9), 1180-6. doi.org/10.1038/ nm911
197. Borsello, T.; Bonny, C. Use of cell-permeable peptides to prevent neuronal degeneration. Trends Mol. Med., 2004, 10 (5), 239-44. doi.org/10.1016/j.molmed.2004.03.008
198. Hammond, J. C.; Meador-Woodruff, J. H.; Haroutunian, V.; McCullumsmith, R. E. AMPA receptor subunit expression in the endoplasmic reticulum in frontal cortex of elderly patients with schizophrenia. PLoS One, 2012, 7 (6), e39190. doi.org/10.1371/ journal.pone.0039190
199. Tucholski, J.; Simmons, M. S.; Pinner, A. L.; Haroutunian, V.; McCullumsmith, R. E.; Meador-Woodruff, J. H. Abnormal Nlinked glycosylation of cortical AMPA receptor subunits in schizophrenia. Schizophr. Res., 2013, 146 (1-3), 177-83. doi.org/ 10.1016/j.schres.2013.01.031