Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 697935, 12 pages
http://dx.doi.org/10.1155/2014/697935
Review Article

Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window

Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8585, Japan

Received 1 February 2014; Accepted 10 April 2014; Published 13 May 2014

Academic Editor: Saverio Bellusci

Copyright © 2014 Hiroyuki Nawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Cohen, “The epidermal growth factor (EGF),” Cancer, vol. 51, no. 10, pp. 1787–1791, 1983. View at Google Scholar · View at Scopus
  2. S. Higashiyama and D. Nanba, “ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk,” Biochimica et Biophysica Acta, vol. 1751, no. 1, pp. 110–117, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. L. Mei and W.-C. Xiong, “Neuregulin 1 in neural development, synaptic plasticity and schizophrenia,” Nature Reviews Neuroscience, vol. 9, no. 6, pp. 437–452, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. T. Futamura, K. Toyooka, S. Iritani et al., “Abnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients,” Molecular Psychiatry, vol. 7, no. 7, pp. 673–682, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Shibuya, E. Komi, R. Wang et al., “Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism,” Journal of Neural Transmission, vol. 117, no. 7, pp. 887–895, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. D. Jeng, Z. Ma, J. W. Barrett, G. McFadden, J. A. Loeb, and K. Essani, “The tanapoxvirus 15L protein is a virus-encoded neuregulin that promotes viral replication in human endothelial cells,” Journal of Virology, vol. 87, no. 6, pp. 3018–3026, 2013. View at Google Scholar
  7. M. Kim, H. Yang, S. K. Kim et al., “Biochemical and functional analysis of smallpox growth factor (SPGF) and anti-SPGF monoclonal antibodies,” Journal of Biological Chemistry, vol. 279, no. 24, pp. 25838–25848, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Y. Galvez-Contreras, A. Quiñones-Hinojosa, and O. Gonzalez-Perez, “The role of EGFR and ErbB family related proteins in the oligodendrocyte specification in germinal niches of the adult mammalian brain,” Frontiers in Cellular Neuroscince, vol. 7, article 258, 2013. View at Google Scholar
  9. C. J. Xian and X. F. Zhou, “EGF family of growth factors: essential roles and functional redundancy in the nerve system,” Frontiers in Bioscience, vol. 9, pp. 85–92, 2004. View at Google Scholar · View at Scopus
  10. H. Nawa and N. Takei, “Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines,” Neuroscience Research, vol. 56, no. 1, pp. 2–13, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. Y. Iwakura and H. Nawa, “ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: pathological implications in schizophrenia and Parkinson's disease,” Frontiers in Cellular Neuroscince, vol. 7, article 4, 2013. View at Google Scholar
  12. M. Jo, D. B. Stolz, J. E. Esplen, K. Dorko, G. K. Michalopoulos, and S. C. Strom, “Cross-talk between epidermal growth factor receptor and c-Met signal pathways in transformed cells,” Journal of Biological Chemistry, vol. 275, no. 12, pp. 8806–8811, 2000. View at Publisher · View at Google Scholar · View at Scopus
  13. H. I. Kornblum, D. S. Yanni, M. C. Easterday, and K. B. Seroogy, “Expression of the EGF receptor family members ErbB2, ErbB3, and ErbB4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells,” Developmental Neuroscience, vol. 22, no. 1-2, pp. 16–24, 2000. View at Google Scholar · View at Scopus
  14. I. J. Fox and H. I. Kornblum, “Developmental profile of ErbB receptors in murine central nervous system: implications for functional interactions,” Journal of Neuroscience Research, vol. 79, no. 5, pp. 584–597, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. Abe, H. Namba, Y. Zheng, and H. Nawa, “In situ hybridization reveals developmental regulation of ErbB1-4 mRNA expression in mouse midbrain: implication of ErbB receptors for dopaminergic neurons,” Neuroscience, vol. 161, no. 1, pp. 95–110, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Neddens, K. N. Fish, L. Tricoire et al., “Conserved interneuron-specific ErbB4 expression in frontal cortex of rodents, monkeys, and humans: implications for schizophrenia,” Biological Psychiatry, vol. 70, no. 7, pp. 636–645, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Nagano, H. Namba, Y. Abe, H. Aoki, N. Takei, and H. Nawa, “In vivo administration of epidermal growth factor and its homologue attenuates developmental maturation of functional excitatory synapses in cortical GABAergic neurons,” European Journal of Neuroscience, vol. 25, no. 2, pp. 380–390, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Birchmeier and K. A. Nave, “Neuregulin-1, a key axonal signal that drives Schwann cell growth and differentiation,” Glia, vol. 56, no. 14, pp. 1491–1497, 2008. View at Google Scholar · View at Scopus
  19. L. Zhang, A. Fletcher-Turner, M. A. Marchionni et al., “Neurotrophic and neuroprotective effects of the neuregulin glial growth factor-2 on dopaminergic neurons in rat primary midbrain cultures,” Journal of Neurochemistry, vol. 91, no. 6, pp. 1358–1368, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Iwakura, R. Wang, Y. Abe et al., “Dopamine-dependent ectodomain shedding and release of epidermal growth factor in developing striatum: target-derived neurotrophic signaling (Part 2),” Journal of Neurochemistry, vol. 118, no. 1, pp. 57–68, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Carlsson, F. R. Schindler, M. Höllerhage et al., “Systemic administration of neuregulin-1β1 protects dopaminergic neurons in a mouse model of Parkinson's disease,” Journal of Neurochemistry, vol. 117, no. 6, pp. 1066–1074, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Fazzari, A. V. Paternain, M. Valiente et al., “Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling,” Nature, vol. 464, no. 7293, pp. 1376–1380, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. A. K. Ting, Y. Chen, L. Wen et al., “Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons,” Journal of Neuroscience, vol. 31, no. 1, pp. 15–25, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Abe, H. Namba, T. Kato, Y. Iwakura, and H. Nawa, “Neuregulin-1 signals from the periphery regulate AMPA receptor sensitivity and expression in GABAergic interneurons in developing neocortex,” Journal of Neuroscience, vol. 31, no. 15, pp. 5699–5709, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. H. Stefansson, E. Sigurdsson, V. Steinthorsdottir et al., “Neuregulin 1 and Susceptibility to Schizophrenia,” The American Journal of Human Genetics, vol. 71, no. 4, pp. 877–892, 2002. View at Google Scholar · View at Scopus
  26. S. Anttila, A. Illi, O. Kampman, K. M. Mattila, T. Lehtimäki, and E. Leinonen, “Association of EGF polymorphism with schizophrenia in Finnish men,” NeuroReport, vol. 15, no. 7, pp. 1215–1218, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. K. Y. Lee, Y. M. Ahn, E. J. Joo et al., “Partial evidence of an association between epidermal growth factor A61G polymorphism and age at onset in male schizophrenia,” Neuroscience Research, vol. 56, no. 4, pp. 356–362, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Hänninen, H. Katila, S. Anttila et al., “Epidermal growth factor a61g polymorphism is associated with the age of onset of schizophrenia in male patients,” Journal of Psychiatric Research, vol. 41, no. 1-2, pp. 8–14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. Y. Watanabe, N. Fukui, T. Muratake, N. Kaneko, and T. Someya, “No association of EGF polymorphism with schizophrenia in a Japanese population,” NeuroReport, vol. 16, no. 4, pp. 403–405, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Tohmi, N. Tsuda, M. Mizuno, N. Takei, P. W. Frankland, and H. Nawa, “Distinct influences of neonatal epidermal growth factor challenge on adult neurobehavioral traits in four mouse strains,” Behavior Genetics, vol. 35, no. 5, pp. 615–629, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Futamura, A. Kakita, M. Tohmi, H. Sotoyama, H. Takahashi, and H. Nawa, “Neonatal perturbation of neurotrophic signaling results in abnormal sensorimotor gating and social interaction in adults: implication for epidermal growth factor in cognitive development,” Molecular Psychiatry, vol. 8, pp. 19–29, 2003. View at Google Scholar
  32. M. Mizuno, R. S. Malta Jr., T. Nagano, and H. Nawa, “Conditioned place preference and locomotor sensitization after repeated administration of cocaine or methamphetamine in rats treated with epidermal growth factor during the neonatal period,” Annals of the New York Academy of Sciences, vol. 1025, pp. 612–618, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Sotoyama, H. Namba, N. Takei, and H. Nawa, “Neonatal exposure to epidermal growth factor induces dopamine D 2-like receptor supersensitivity in adult sensorimotor gating,” Psychopharmacology, vol. 191, no. 3, pp. 783–792, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Watanabe, S. Hashimoto, A. Kakita et al., “Neonatal impact of leukemia inhibitory factor on neurobehavioral development in rats,” Neuroscience Research, vol. 48, no. 3, pp. 345–353, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Tohmi, N. Tsuda, Y. Watanabe, A. Kakita, and H. Nawa, “Perinatal inflammatory cytokine challenge results in distinct neurobehavioral alterations in rats: implication in psychiatric disorders of developmental origin,” Neuroscience Research, vol. 50, no. 1, pp. 67–75, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Tohmi, N. Tsuda, Y. Zheng et al., “The cellular and behavioral consequences of interleukin-1 alpha penetration through the blood-brain barrier of neonatal rats: a critical period for efficacy,” Neuroscience, vol. 150, no. 1, pp. 234–250, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. N. Tsuda, M. Mizuno, T. Yamanaka, T. Komurasaki, M. Yoshimoto, and H. Nawa, “Common behavioral influences of the ErbB1 ligands transforming growth factor alpha and epiregulin administered to mouse neonates,” Brain and Development, vol. 30, no. 8, pp. 533–543, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Kato, Y. Abe, H. Sotoyama et al., “Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia,” Molecular Psychiatry, vol. 16, no. 3, pp. 307–320, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. R. P. Kleshcheva, “The development of components of the blood-brain barrier in the neocortex of the white rat,” Arkhiv Anatomii, Gistologii i Embriologii, vol. 95, no. 11, pp. 22–26, 1988. View at Google Scholar · View at Scopus
  40. A. J. Kastin, V. Akerstrom, and W. Pan, “Neuregulin-1-β1 enters brain and spinal cord by receptor-mediated transport,” Journal of Neurochemistry, vol. 88, no. 4, pp. 965–970, 2004. View at Google Scholar · View at Scopus
  41. T. W. Rösler, C. Depboylu, O. Arias-Carrión et al., “Biodistribution and brain permeability of the extracellular domain of neuregulin-1-β1,” Neuropharmacology, vol. 61, no. 8, pp. 1413–1418, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. K. B. Seroogy, S. Numan, C. M. Gall, D. C. Lee, and H. I. Kornblum, “Expression of EGF receptor mRNA in rat nigrostriatal system,” NeuroReport, vol. 6, no. 1, pp. 105–108, 1994. View at Google Scholar · View at Scopus
  43. M. Mizuno, H. Sotoyama, E. Narita et al., “A cyclooxygenase-2 inhibitor ameliorates behavioral impairments induced by striatal administration of epidermal growth factor,” Journal of Neuroscience, vol. 27, no. 38, pp. 10116–10127, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Sakai, M. Kashiwahara, A. Kakita, and H. Nawa, “An attempt of non-human primate modeling of schizophrenia with neonatal challenges of epidermal growth factor,” Behavioral Pharmacology in Addiction Research & Therapy, vol. 5, article 170, 2014. View at Publisher · View at Google Scholar
  45. T. Kato, A. Kasai, M. Mizuno et al., “Phenotypic characterization of transgenic mice overexpressing neuregulin-1,” PLoS ONE, vol. 5, no. 12, Article ID e14185, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. T. Eda, M. Mizuno, K. Araki et al., “Neurobehavioral deficits of epidermal growth factor-overexpressing transgenic mice: impact on dopamine metabolism,” Neuroscience Letters, vol. 547, pp. 21–25, 2013. View at Google Scholar
  47. C. M. O'Tuathaigh, D. Babovic, G. O'Meara, J. J. Clifford, D. T. Croke, and J. L. Waddington, “Susceptibility genes for schizophrenia: characterisation of mutant mouse models at the level of phenotypic behaviour,” Neuroscience and Biobehavioral Reviews, vol. 31, no. 1, pp. 60–78, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Mouri, T. Nagai, D. Ibi, and K. Yamada, “Animal models of schizophrenia for molecular and pharmacological intervention and potential candidate molecules,” Neurobiology of Disease, vol. 53, pp. 61–74, 2013. View at Google Scholar
  49. T. Karl, “Neuregulin 1: a prime candidate for research into gene-environment interactions in schizophrenia? Insights from genetic rodent models,” Frontiers in Behavioral Neuroscience, vol. 7, article 106, 2013. View at Google Scholar
  50. A. Oyagi, Y. Oida, K. Kakefuda et al., “Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice,” PLoS ONE, vol. 4, no. 10, Article ID e7461, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. C. G. Hahn, H. Y. Wang, D. S. Cho et al., “Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia,” Nature Medicine, vol. 12, no. 7, pp. 824–828, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Karl, L. Duffy, A. Scimone, R. P. Harvey, and P. R. Schofield, “Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: Implications for understanding schizophrenia,” Genes, Brain and Behavior, vol. 6, no. 7, pp. 677–687, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. I. del Pino, C. García-Frigola, N. Dehorter et al., “ErbB4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes,” Neuron, vol. 79, no. 6, pp. 1152–1168, 2013. View at Google Scholar
  54. Y. Watanabe, T. Someya, and H. Nawa, “Cytokine hypothesis of schizophrenia pathogenesis: evidence from human studies and animal models,” Psychiatry and Clinical Neurosciences, vol. 64, no. 3, pp. 217–230, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. H. Namba, T. Nagano, Y. Iwakura et al., “Transforming growth factor alpha attenuates the functional expression of AMPA receptors in cortical GABAergic neurons,” Molecular and Cellular Neuroscience, vol. 31, no. 4, pp. 628–641, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. H. Namba, Y. Zheng, Y. Abe, and H. Nawa, “Epidermal growth factor administered in the periphery influences excitatory synaptic inputs onto midbrain dopaminergic neurons in postnatal mice,” Neuroscience, vol. 158, no. 4, pp. 1731–1741, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. D. Yokomaku, H. Jourdi, A. Kakita et al., “ErbB1 receptor ligands attenuate the expression of synaptic scaffolding proteins, GRIP1 and SAP97, in developing neocortex,” Neuroscience, vol. 136, no. 4, pp. 1037–1047, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Sotoyama, Y. Zheng, Y. Iwakura et al., “Pallidal hyperdopaminergic innervation underlying d2 receptor-dependent behavioral deficits in the schizophrenia animal model established by EGF,” PLoS ONE, vol. 6, no. 10, Article ID e25831, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Zheng, A. Watakabe, M. Takada et al., “Expression of ErbB4 in substantia nigra dopamine neurons of monkeys and humans,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 33, no. 4, pp. 701–706, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. I. H. Deakin, W. Nissen, A. J. Law et al., “Transgenic overexpression of the type I isoform of neuregulin 1 affects working memory and hippocampal oscillations but not long-term potentiation,” Cerebral Cortex, vol. 22, no. 7, pp. 1520–1529, 2012. View at Google Scholar
  61. D. M. Yin, Y. J. Chen, Y. S. Lu et al., “Reversal of behavioral deficits and synaptic dysfunction in mice overexpressing neuregulin 1,” Neuron, vol. 78, no. 4, pp. 644–657, 2013. View at Google Scholar
  62. X. Luo, W. He, X. Hu, and R. Yan, “Reversible overexpression of Bace1-cleaved neuregulin-1 N-terminal fragment induces schizophrenia-like phenotypes in mice,” Biological Psychiatry, 2013. View at Publisher · View at Google Scholar
  63. M. L. Perreault, A. Hasbi, M. Alijaniaram et al., “The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: Increased high affinity state following amphetamineandin schizophrenia,” Journal of Biological Chemistry, vol. 285, no. 47, pp. 36625–36634, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. C. R. Gerfen and D. J. Surmeier, “Modulation of striatal projection systems by dopamine,” Annual Review of Neuroscience, vol. 34, pp. 441–466, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Cazorla, F. D. de Carvalho, M. O. Chohan et al., “Dopamine d2 receptors regulate the anatomical and functional balance of Basal Ganglia circuitry,” Neuron, vol. 81, no. 1, pp. 153–164, 2014. View at Google Scholar
  66. H. Sotoyama, H. Namba, S. Chiken, A. Nambu, and H. Nawa, “Exposure to the cytokine EGF leads to abnormal hyperactivity of pallidal GABA neurons: implications for schizophrenia and its modeling,” Journal of Neurochemistry, vol. 126, no. 4, pp. 518–528, 2013. View at Google Scholar
  67. M. Mizuno, H. Sotoyama, H. Namba et al., “ErbB inhibitors ameliorate behavioral impairments of an animal model for schizophrenia: implication of their dopamine-modulatory actions,” Translational Psychiatry, vol. 3, article e252, 2013. View at Google Scholar
  68. D. L. Levy, A. B. Sereno, D. C. Gooding, and G. A. O'Driscoll, “Eye tracking dysfunction in schizophrenia: characterization and pathophysiology,” Current Topics in Behavioral Neurosciences, vol. 4, pp. 311–347, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. M. Furman and M. Gur, “And yet it moves: perceptual illusions and neural mechanisms of pursuit compensation during smooth pursuit eye movements,” Neuroscience and Biobehavioral Reviews, vol. 36, no. 1, pp. 143–151, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Higashiyama, D. Nanba, H. Nakayama, H. Inoue, and S. Fukuda, “Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands,” Journal of Biochemistry, vol. 150, no. 1, pp. 15–22, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. M. R. Schneider and E. Wolf, “The epidermal growth factor receptor ligands at a glance,” Journal of Cellular Physiology, vol. 218, no. 3, pp. 460–466, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. H. C. Crawford, P. J. Dempsey, G. Brown, L. Adam, and M. L. Moss, “ADAM10 as a therapeutic target for cancer and inflammation,” Current Pharmaceutical Design, vol. 15, no. 20, pp. 2288–2299, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. L. Peng, B. Li, T. Du et al., “Astrocytic transactivation by α2A-adrenergic and 5-HT2B serotonergic signaling,” Neurochemistry International, vol. 57, no. 4, pp. 421–431, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. Iwakura, Y. Zheng, M. Sibilia et al., “Qualitative and quantitative re-evaluation of epidermal growth factor-ErbB1 action on developing midbrain dopaminergic neurons in vivo and in vitro: target-derived neurotrophic signaling (Part 1),” Journal of Neurochemistry, vol. 118, no. 1, pp. 45–56, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. S. Yoon and J. H. Baik, “Dopamine D2 receptor-mediated epidermal growth factor receptor transactivation through a disintegrin and metalloprotease regulates dopaminergic neuron development via extracellular signal-related kinase activation,” The Journal of Biological Chemistry, vol. 288, no. 40, pp. 28435–28446, 2013. View at Google Scholar
  76. G. C. O'Keeffe, P. Tyers, D. Aarsland, J. W. Dalley, R. A. Barker, and M. A. Caldwellf, “Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 21, pp. 8754–8759, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. U. Meyer, J. Feldon, and B. K. Yee, “A review of the fetal brain cytokine imbalance hypothesis of schizophrenia,” Schizophrenia Bulletin, vol. 35, no. 5, pp. 959–972, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Bauer, B. J. Kerr, and P. H. Patterson, “The neuropoietic cytokine family in development, plasticity, disease and injury,” Nature Reviews Neuroscience, vol. 8, no. 3, pp. 221–232, 2007. View at Publisher · View at Google Scholar · View at Scopus