Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

Molecular Psychiatry volume 16, pages 307–320 (2011)Cite this article

Subjects

A Corrigendum to this article was published on 18 June 2013

Abstract

Neuregulin-1 (NRG1) is implicated in the etiology or pathology of schizophrenia, although its biological roles in this illness are not fully understood. Human midbrain dopaminergic neurons highly express NRG1 receptors (ErbB4). To test its neuropathological role in the neurodevelopmental hypothesis of schizophrenia, we administered type-1 NRG1 protein to neonatal mice and evaluated the immediate and subsequent effects on dopaminergic neurons and their associated behaviors. Peripheral NRG1 administration activated midbrain ErbB4 and elevated the expression, phosphorylation and enzyme activity of tyrosine hydroxylase (TH), which ultimately increased dopamine levels. The hyperdopaminergic state was sustained in the medial prefrontal cortex after puberty. There were marked increases in dopaminergic terminals and TH levels. In agreement, higher amounts of dopamine were released from this brain region of NRG1-treated mice following high potassium stimulation. Furthermore, NRG1-treated mice exhibited behavioral impairments in prepulse inhibition, latent inhibition, social behaviors and hypersensitivity to methamphetamine. However, there were no gross abnormalities in brain structures or other phenotypic features of neurons and glial cells. Collectively, our findings provide novel insights into neurotrophic contribution of NRG1 to dopaminergic maldevelopment and schizophrenia pathogenesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002; 71: 877–892.

    PubMed  PubMed Central  Google Scholar 

  2. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 2008; 320: 539–543.

    Article  CAS  PubMed  Google Scholar 

  3. Chong VZ, Thompson M, Beltaifa S, Webster MJ, Law AJ, Weickert CS . Elevated neuregulin-1 and ErbB4 protein in the prefrontal cortex of schizophrenic patients. Schizophr Res 2008; 100: 270–280.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hashimoto R, Straub RE, Weickert CS, Hyde TM, Kleinman JE, Weinberger DR . Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia. Mol Psychiatry 2004; 9: 299–307.

    Article  CAS  PubMed  Google Scholar 

  5. Law AJ, Lipska BK, Weickert CS, Hyde TM, Straub RE, Hashimoto R et al. Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5′ SNPs associated with the disease. Proc Natl Acad Sci USA 2006; 103: 6747–6752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Petryshen TL, Middleton FA, Kirby A, Aldinger KA, Purcell S, Tahl AR et al. Support for involvement of neuregulin 1 in schizophrenia pathophysiology. Mol Psychiatry 2005; 10: 366–374.

    Article  CAS  PubMed  Google Scholar 

  7. Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 2004; 61: 774–780.

    Article  PubMed  Google Scholar 

  8. Zornberg GL, Buka SL, Tsuang MT . Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study. Am J Psychiatry 2000; 157: 196–202.

    Article  CAS  PubMed  Google Scholar 

  9. Nadri C, Belmaker RH, Agam G . Oxygen restriction of neonate rats elevates neuregulin-1alpha isoform levels: possible relationship to schizophrenia. Neurochem Int 2007; 51: 447–450.

    Article  CAS  PubMed  Google Scholar 

  10. Parker MW, Chen Y, Hallenbeck JM, Ford BD . Neuregulin expression after focal stroke in the rat. Neurosci Lett 2002; 334: 169–172.

    Article  CAS  PubMed  Google Scholar 

  11. Tokita Y, Keino H, Matsui F, Aono S, Ishiguro H, Higashiyama S et al. Regulation of neuregulin expression in the injured rat brain and cultured astrocytes. J Neurosci 2001; 21: 1257–1264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Flames N, Long JE, Garratt AN, Fischer TM, Gassmann M, Birchmeier C et al. Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1. Neuron 2004; 44: 251–261.

    Article  CAS  PubMed  Google Scholar 

  13. Taveggia C, Thaker P, Petrylak A, Caporaso GL, Toews A, Falls DL et al. Type III neuregulin-1 promotes oligodendrocyte myelination. Glia 2008; 56: 284–293.

    Article  PubMed  Google Scholar 

  14. Krivosheya D, Tapia L, Levinson JN, Huang K, Kang Y, Hines R et al. ErbB4-neuregulin signaling modulates synapse development and dendritic arborization through distinct mechanisms. J Biol Chem 2008; 283: 32944–32956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. López-Bendito G, Cautinat A, Sánchez JA, Bielle F, Flames N, Garratt AN et al. Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 2006; 125: 127–142.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen YJ, Johnson MA, Lieberman MD, Goodchild RE, Schobel S, Lewandowski N et al. Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components. J Neurosci 2008; 28: 6872–6883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ehrlichman RS, Luminais SN, White SL, Rudnick ND, Ma N, Dow HC et al. Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions. Brain Res 2009; 1294: 116–127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. O’Tuathaigh CM, Babovic D, O’Sullivan GJ, Clifford JJ, Tighe O, Croke DT et al. Phenotypic characterization of spatial cognition and social behavior in mice with ‘knockout’ of the schizophrenia risk gene neuregulin 1. Neuroscience 2007; 147: 18–27.

    Article  PubMed  Google Scholar 

  19. Rimer M, Barrett DW, Maldonado MA, Vock VM, Gonzalez-Lima F . Neuregulin-1 immunoglobulin-like domain mutant mice: clozapine sensitivity and impaired latent inhibition. Neuroreport 2005; 16: 271–275.

    Article  CAS  PubMed  Google Scholar 

  20. Abe Y, Namba H, Zheng Y, Nawa H . In situ hybridization reveals developmental regulation of ErbB1-4 mRNA expression in mouse midbrain: implication of ErbB receptors for dopaminergic neurons. Neuroscience 2009; 161: 95–110.

    Article  CAS  PubMed  Google Scholar 

  21. Zheng Y, Watakabe A, Takada M, Kakita A, Namba H, Takahashi H et al. Expression of ErbB4 in substantia nigra dopamine neurons of monkeys and humans. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 701–706.

    Article  PubMed  Google Scholar 

  22. Fox IJ, Kornblum HI . Developmental profile of ErbB receptors in murine central nervous system: implications for functional interactions. J Neurosci Res 2005; 79: 584–597.

    Article  CAS  PubMed  Google Scholar 

  23. Neddens J, Vullhorst D, Paredes D, Buonanno A . Neuregulin links dopaminergic and glutamatergic neurotransmission to control hippocampal synaptic plasticity. Commun Integr Biol 2009; 2: 261–264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lewis DA, Levitt P . Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 2002; 25: 409–432.

    Article  CAS  PubMed  Google Scholar 

  25. Murray RM, Lewis SW . Is schizophrenia a neurodevelopmental disorder? Br Med J 1987; 295: 681–682.

    Article  CAS  Google Scholar 

  26. Weinberger DR . Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44: 660–669.

    Article  CAS  PubMed  Google Scholar 

  27. Winterer G, Weinberger DR . Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci 2004; 27: 683–690.

    Article  CAS  PubMed  Google Scholar 

  28. Ozaki M, Tohyama K, Kishida H, Buonanno A, Yano R, Hashikawa T . Roles of neuregulin in synaptogenesis between mossy fibers and cerebellar granule cells. J Neurosci Res 2000; 59: 612–623.

    Article  CAS  PubMed  Google Scholar 

  29. Umetsu M, Tsumoto K, Hara M, Ashish K, Goda S, Adschiri T et al. How additives influence the refolding of immunoglobulin-folded proteins in a stepwise dialysis system. Spectroscopic evidence for highly efficient refolding of a single-chain Fv fragment. J Biol Chem 2003; 278: 8979–8987.

    Article  CAS  PubMed  Google Scholar 

  30. Tohmi M, Tsuda N, Zheng Y, Mizuno M, Sotoyama H, Shibuya M 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 2007; 150: 234–250.

    Article  CAS  PubMed  Google Scholar 

  31. Kapur S, VanderSpek SC, Brownlee BA, Nobrega JN . Antipsychotic dosing in preclinical models is often unrepresentative of the clinical condition: a suggested solution based on in vivo occupancy. J Pharmacol Exp Ther 2003; 305: 625–631.

    Article  CAS  PubMed  Google Scholar 

  32. Lim EP, Verma V, Nagarajah R, Dawe GS . Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task. Psychopharmacology (Berl) 2007; 191: 297–310.

    Article  CAS  Google Scholar 

  33. Martinez-Gras I, Rubio G, del Manzano BA, Rodriguez-Jimenez R, Garcia-Sanchez F, Bagney A et al. The relationship between prepulse inhibition and general psychopathology in patients with schizophrenia treated with long-acting risperidone. Schizophr Res 2009; 115: 215–221.

    Article  PubMed  Google Scholar 

  34. Namba H, Zheng Y, Abe Y, Nawa H . Epidermal growth factor administered in the periphery influences excitatory synaptic inputs onto midbrain dopaminergic neurons in postnatal mice. Neuroscience 2009; 158: 1731–1741.

    Article  CAS  PubMed  Google Scholar 

  35. Tohmi M, Tsuda N, Mizuno M, Takei N, Frankland PW, Nawa H . Distinct influences of neonatal epidermal growth factor challenge on adult neurobehavioral traits in four mouse strains. Behav Genet 2005; 35: 615–629.

    Article  PubMed  Google Scholar 

  36. Frankland PW, Josselyn SA, Anagnostaras SG, Kogan JH, Takahashi E, Silva AJ . Consolidation of CS and US representations in associative fear conditioning. Hippocampus 2004; 14: 557–569.

    Article  PubMed  Google Scholar 

  37. Caldarone BJ, Duman CH, Picciotto MR . Fear conditioning and latent inhibition in mice lacking the high affinity subclass of nicotinic acetylcholine receptors in the brain. Neuropharmacology 2000; 39: 2779–2784.

    Article  CAS  PubMed  Google Scholar 

  38. Brown HE, Garcia MM, Harlan RE . A two focal plane method for digital quantification of nuclear immunoreactivity in large brain areas using NIH-image software. Brain Res Brain Protoc 1998; 2: 264–272.

    Article  CAS  Google Scholar 

  39. Mizuno M, Sotoyama H, Narita E, Kawamura H, Namba H, Zheng Y et al. A cyclooxygenase-2 inhibitor ameliorates behavioral impairments induced by striatal administration of epidermal growth factor. J Neurosci 2007; 27: 10116–10127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Futamura T, Kakita A, Tohmi M, Sotoyama H, Takahashi H, Nawa H . Neonatal perturbation of neurotrophic signaling results in abnormal sensorimotor gating and social interaction in adults: implication for epidermal growth factor in cognitive development. Mol Psychiatry 2003; 8: 19–29.

    Article  CAS  PubMed  Google Scholar 

  41. Liu Y, Tao YM, Woo RS, Xiong WC, Mei L . Stimulated ErbB4 internalization is necessary for neuregulin signaling in neurons. Biochem Biophys Res Commun 2007; 354: 505–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fujisawa H, Okuno S . Regulatory mechanism of tyrosine hydroxylase activity. Biochem Biophys Res Commun 2005; 338: 271–276.

    Article  CAS  PubMed  Google Scholar 

  43. Ozaki M, Sasner M, Yano R, Lu HS, Buonanno A . Neuregulin-beta induces expression of an NMDA-receptor subunit. Nature 1997; 390: 691–694.

    Article  CAS  PubMed  Google Scholar 

  44. Sardi SP, Murtie J, Koirala S, Patten BA, Corfas G . Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell 2006; 127: 185–197.

    Article  CAS  PubMed  Google Scholar 

  45. Roy K, Murtie JC, El-Khodor BF, Edgar N, Sardi SP, Hooks BM et al. Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders. Proc Natl Acad Sci USA 2007; 104: 8131–8136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Broersen LM, Feldon J, Weiner I . Dissociative effects of apomorphine infusions into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine-induced locomotion. Neuroscience 1999; 94: 39–46.

    Article  CAS  PubMed  Google Scholar 

  47. Grillon C, Ameli R, Charney DS, Krystal J, Braff D . Startle gating deficits occur across prepulse intensities in schizophrenic patients. Biol Psychiatry 1992; 32: 939–943.

    Article  CAS  PubMed  Google Scholar 

  48. Stankovic K, Rio C, Xia A, Sugawara M, Adams JC, Liberman MC et al. Survival of adult spiral ganglion neurons requires erbB receptor signaling in the inner ear. J Neurosci 2004; 24: 8651–8661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kumari V, Soni W, Sharma T . Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics. Schizophr Res 2002; 55: 139–146.

    Article  PubMed  Google Scholar 

  50. Gray NS, Pickering AD, Hemsley DR, Dawling S, Gray JA . Abolition of latent inhibition by a single 5 mg dose of d-amphetamine in man. Psychopharmacology (Berl) 1992; 107: 425–430.

    Article  CAS  Google Scholar 

  51. Peleg-Raibstein D, Knuesel I, Feldon J . Amphetamine sensitization in rats as an animal model of schizophrenia. Behav Brain Res 2008; 191: 190–201.

    Article  CAS  PubMed  Google Scholar 

  52. Baruch I, Hemsley DR, Gray JA . Differential performance of acute and chronic schizophrenics in a latent inhibition task. J Nerv Ment Dis 1998; 176: 598–606.

    Article  Google Scholar 

  53. Nawa H, Takahashi M, Patterson PH . Cytokine and growth factor involvement in schizophrenia-support for the developmental model. Mol Psychiatry 2000; 5: 594–603.

    Article  CAS  PubMed  Google Scholar 

  54. Thuret S, Alavian KN, Gassmann M, Lloyd CK, Smits SM, Smidt MP et al. The neuregulin receptor, ErbB4, is not required for normal development and adult maintenance of the substantia nigra pars compacta. J Neurochem 2004; 91: 1302–1311.

    Article  CAS  PubMed  Google Scholar 

  55. Hu Z, Cooper M, Crockett DP, Zhou R . Differentiation of the midbrain dopaminergic pathways during mouse development. J Comp Neurol 2004; 476: 301–311.

    Article  PubMed  Google Scholar 

  56. Kalsbeek A, Voorn P, Buijs RM, Pool CW, Uylings HB . Development of the dopaminergic innervation in the prefrontal cortex of the rat. J Comp Neurol 1998; 269: 58–72.

    Article  Google Scholar 

  57. Falls FL . Neuregulins: functions, forms, and signaling strategies. Exp Cell Res 2003; 284: 14–30.

    Article  CAS  PubMed  Google Scholar 

  58. Harrison PJ, Law AJ . Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry 2006; 60: 132–140.

    Article  CAS  PubMed  Google Scholar 

  59. Mei L, Xiong WC . Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 2008; 9: 437–452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Li Q, Loeb JA . Neuregulin-heparan-sulfate proteoglycan interactions produce sustained erbB receptor activation required for the induction of acetylcholine receptors in muscle. J Biol Chem 2001; 276: 38068–38075.

    CAS  PubMed  Google Scholar 

  61. Brummelte S, Teuchert-Noodt G . Postnatal development of dopamine innervation in the amygdala and the entorhinal cortex of the gerbil (Meriones unguiculatus). Brain Res 2006; 1125: 9–16.

    Article  CAS  PubMed  Google Scholar 

  62. Deakin IH, Law AJ, Oliver PL, Schwab MH, Nave KA, Harrison PJ et al. Behavioural characterization of neuregulin 1 type I overexpressing transgenic mice. Neuroreport 2009; 20: 1523–1528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Canoll PD, Musacchio JM, Hardy R, Reynolds R, Marchionni MA, Salzer JL . GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors. Neuron 1996; 17: 229–243.

    Article  CAS  PubMed  Google Scholar 

  64. Lieberman JA, Kane JM, Alvir J . Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology (Berl) 1987; 91: 415–433.

    Article  CAS  Google Scholar 

  65. Clemens KJ, Van Nieuwenhuyzen PS, Li KM, Cornish JL, Hunt GE, McGregor IS . MDMA (‘ecstasy’), methamphetamine and their combination: long-term changes in social interaction and neurochemistry in the rat. Psychopharmacology (Berl) 2004; 173: 318–325.

    Article  CAS  Google Scholar 

  66. Lipska BK, Weinberger DR . To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology 2000; 23: 223–239.

    Article  CAS  PubMed  Google Scholar 

  67. Hernandez L, Hoebel BG . Chronic clozapine selectively decreases prefrontal cortex dopamine as shown by simultaneous cortical, accumbens, and striatal microdialysis in freely moving rats. Pharmacol Biochem Behav 1995; 52: 581–589.

    Article  CAS  PubMed  Google Scholar 

  68. Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR . Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 2001; 156: 117–154.

    Article  CAS  PubMed  Google Scholar 

  69. Keith VA, Mansbach RS, Geyer MA . Failure of haloperidol to block the effects of phencyclidine and dizocilpine on prepulse inhibition of startle. Biol Psychiatry 1991; 30: 557–566.

    Article  CAS  PubMed  Google Scholar 

  70. Le Pen G, Moreau JL . Disruption of prepulse inhibition of startle reflex in a neurodevelopmental model of schizophrenia: reversal by clozapine, olanzapine and risperidone but not by haloperidol. Neuropsychopharmacology 2002; 27: 1–11.

    Article  CAS  PubMed  Google Scholar 

  71. Tamminga CA . The neurobiology of cognition in schizophrenia. J Clin Psychiatry 2006; 67 (Suppl 9): 9–13.

    CAS  PubMed  Google Scholar 

  72. Jaaro-Peled H, Hayashi-Takagi A, Seshadri S, Kamiya A, Brandon NJ, Sawa A . Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1-ErbB4 and DISC1. Trends Neurosci 2009; 32: 485–495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Shi L, Fatemi SH, Sidwell RW, Patterson PH . Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 2003; 23: 297–302.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Decker MJ, Hue GE, Caudle WM, Miller GW, Keating GL, Rye DB . Episodic neonatal hypoxia evokes executive dysfunction and regionally specific alterations in markers of dopamine signalling. Neuroscience 2003; 117: 417–425.

    Article  CAS  PubMed  Google Scholar 

  75. Meyer U, Feldon J . Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia. Psychopharmacology (Berl) 2009; 206: 587–602.

    Article  CAS  Google Scholar 

  76. Romero E, Guaza C, Castellano B, Borrell J . Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia. Mol Psychiatry 2008; e-pub ahead of print 15 April 2008; doi:10.1038/mp.2008.44.

    Article  PubMed  Google Scholar 

  77. Nawa H, Takei N . Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines. Neurosci Res 2006; 56: 2–13.

    Article  CAS  PubMed  Google Scholar 

  78. Tohmi M, Tsuda N, Watanabe Y, Kakita A, Nawa H . Perinatal inflammatory cytokine challenge results in distinct neurobehavioral alterations in rats: implication in psychiatric disorders of developmental origin. Neurosci Res 2004; 50: 67–75.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr Jourdi for proofreading. This work was supported by Health and Labor Sciences Research Grants, a grant for Promotion of Niigata University Research Projects, Core Research for Evolutional Science and Technology from the JST Corporation and a grant-in-aid from the Ministry of Health, Labor and Welfare, Japan.

Author information

Authors and Affiliations

  1. Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan

    T Kato, Y Abe, H Sotoyama & H Nawa

  2. Department of Pathological Neuroscience, Resource Branch for Brain Disease Research, Brain Research Institute, Niigata University, Niigata, Japan

    A Kakita & H Takahashi

  3. Department of Molecular Genetics, Niigata University, Niigata, Japan

    R Kominami & S Hirokawa

  4. Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan

    M Ozaki

Authors
  1. T Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Sotoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Kakita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R Kominami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Hirokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Ozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H Nawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Nawa.

Additional information

Note added in proof: We also tested the in vivo activity of the misfolded NRG1β1 in the peak 1 of the cation-exchange chromatography (Supplementary Figure S1) and did not detect its effects on TH and dopamine content (Supplementary Figure S8).

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kato, T., Abe, Y., Sotoyama, H. et al. Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia. Mol Psychiatry 16, 307–320 (2011). https://doi.org/10.1038/mp.2010.10

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2010.10

Keywords

This article is cited by

Search

Advanced search

Quick links