Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders
Open accessAbstract
Several psychiatric disorders are associated with white matter defects, suggesting that oligodendrocyte (OL) abnormalities underlie some aspects of these diseases. Neuregulin 1 (NRG1) and its receptor, erbB4, are genetically linked with susceptibility to schizophrenia and bipolar disorder. In vitro studies suggest that NRG1-erbB signaling is important for OL development. To test whether erbB signaling contributes to psychiatric disorders by regulating the structure or function of OLs, we analyzed transgenic mice in which erbB signaling is blocked in OLs in vivo . Here we show that loss of erbB signaling leads to changes in OL number and morphology, reduced myelin thickness, and slower conduction velocity in CNS axons. Furthermore, these transgenic mice have increased levels of dopamine receptors and transporters and behavioral alterations consistent with neuropsychiatric disorders. These results indicate that defects in white matter can cause alterations in dopaminergic function and behavior relevant to neuropsychiatric disorders.
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Cycles of demyelination and remyelination in multiple sclerosis are associated with fluctuations in conduction velocity and symptomatology, including psychotic symptomatology.
“Such a possibility would be akin to the cycles of demyelination and remyelination often experienced by patients with multiple sclerosis 72 : cycles that have been shown to be associated with fluctuations in conduction velocity 46 and symptomatology, including psychotic symptomatology.[73][74][75]”
From Schizophrenia, myelination, and delayed corollary discharges: a hypothesis (2012) · cites this paper as [75]
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Cites
The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review.
Prut, L., & Belzung, C. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01272-x · Cited by 3,190 · see citing works
Neuregulin 1 and Susceptibility to Schizophrenia
Stefánsson, H., Pétursson, H., Sigurðsson, E., Steinthórsdóttir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342734 · Cited by 1,671 · see citing works
Self-citationMice with Reduced NMDA Receptor Expression Display Behaviors Related to Schizophrenia
Mohn, A. R., Gainetdinov, R. R., Caron, M. G., & Koller, B. H. (1999) · Cell · doi:10.1016/s0092-8674(00)81972-8 · Cited by 1,075 · see citing works
The Structure of Negative Symptoms Within Schizophrenia: Implications for Assessment
Blanchard, J. J., & Cohen, A. S. (2005) · Schizophrenia Bulletin · doi:10.1093/schbul/sbj013 · Cited by 649 · see citing works
Altered neuregulin 1–erbB4 signaling contributes to NMDA> receptor hypofunction in schizophrenia
Hahn, C.-G., Wang, H.-Y., Cho, D.-S., Talbot, K., Gur, R. E., Berrettini, W. H., Bakshi, K. P., Kamins, J., Borgmann‐Winter, K. E., Siegel, S. J., et al. (2006) · Nature Medicine · doi:10.1038/nm1418 · Cited by 564 · see citing works
Belachew, S. M., Chittajallu, R., Aguirre, A. A., Yuan, X. Q., Kirby, M., Anderson, S. M., & Gallo, V. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200210110 · Cited by 489 · see citing works
Axonal regulation of myelination by neuregulin 1
Nave, K., & Salzer, J. L. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.08.008 · Cited by 452 · see citing works
Law, A. J., Lipska, B. K., Weickert, C. S., Hyde, T. M., Straub, R. E., Hashimoto, R., Harrison, P. J., Kleinman, J. E., & Weinberger, D. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602002103 · Cited by 403 · see citing works
Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia
Corfas, G., Roy, K., & Buxbaum, J. D. (2004) · Nature Neuroscience · doi:10.1038/nn1258 · Cited by 388 · see citing works
Self-citationMallon, B. S., Shick, H. E., Kidd, G. J., & Macklin, W. B. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00876.2002 · Cited by 382 · see citing works
Neuregulin and erbB Receptors Play a Critical Role in Neuronal Migration
Río, C., Rieff, H. I., Qi, P., & Corfas, G. (1997) · Neuron · doi:10.1016/s0896-6273(00)80346-3 · Cited by 382 · see citing works
Self-citationSardi, S. P., Murtie, J. C., Koirala, S., Patten, B. A., & Corfas, G. (2006) · Cell · doi:10.1016/j.cell.2006.07.037 · Cited by 349 · see citing works
Self-citationLaruelle, M. (2000) · Brain research. Brain research reviews · doi:10.1016/s0165-0173(99)00054-5 · Cited by 347 · see citing works
Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia
Hashimoto, R., Straub, R. E., Weickert, C. S., Hyde, T. M., Kleinman, J. E., & Weinberger, D. R. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001434 · Cited by 283 · see citing works
The involvement of ErbB4 with schizophrenia: Association and expression studies
Silberberg, G., Darvasi, A., Pinkas‐Kramarski, R., & Navon, R. (2006) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30275 · Cited by 251 · see citing works
Aguirre, A. A., & Gallo, V. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3572-04.2004 · Cited by 224 · see citing works
Aberrant responses in social interaction of dopamine transporter knockout mice
Rodriguiz, R. M., Chu, R., Caron, M. G., & Wetsel, W. C. (2003) · Behavioural Brain Research · doi:10.1016/s0166-4328(03)00187-6 · Cited by 221 · see citing works
Neuregulin 1–erbB Signaling Is Necessary for Normal Myelination and Sensory Function
Chen, S., Velardez, M. O., Warot, X. M., Yu, Z.-X., Miller, S. J., Cros, D. P., & Corfas, G. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3785-05.2006 · Cited by 192 · see citing works
Self-citationNorton, N., Moskvina, V., Morris, D. W., Bray, N. J., Zammit, S., Williams, N. M., Williams, H. J., Preece, A. C., Dwyer, S., Wilkinson, J. C., et al. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30236 · Cited by 185 · see citing works
Armstrong, R. C., Le, T. Q., Frost, E. E., Borke, R. C., & Vana, A. C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-19-08574.2002 · Cited by 178 · see citing works
Dracheva, S. M., Davis, K. L., Chin, B., Woo, D. A., Schmeidler, J., & Haroutunian, V. H. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.08.012 · Cited by 178 · see citing works
Prévot, V., Río, C., Cho, G. J., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00230.2003 · Cited by 177 · see citing works
Dopamine and the Diseased Brain
Kienast, T., & Heinz, A. (2006) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152706784111560 · Cited by 172 · see citing works
Chen, S., Río, C., Ji, R., Dikkes, P., Coggeshall, R. E., Woolf, C. J., & Corfas, G. (2003) · Nature Neuroscience · doi:10.1038/nn1139 · Cited by 167 · see citing works
Self-citationNeuregulin-1 (NRG-1) mRNA and protein in the adult human brain
Law, A. J., Weickert, C. S., Hyde, T. M., Kleinman, J. E., & Harrison, P. J. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.04.026 · Cited by 160 · see citing works
Behavioral characteristics of a nervous system-specific erbB4 knock-out mouse
Golub, M. S., Germann, S. L., & Lloyd, K. C. K. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.11.010 · Cited by 155 · see citing works
Neuroanatomical abnormalities as risk factors for bipolar disorder
Hájek, T., CARREY, N. J., & Alda, M. (2005) · Bipolar Disorders · doi:10.1111/j.1399-5618.2005.00238.x · Cited by 155 · see citing works
A diffusion tensor imaging study of white matter in obsessive–compulsive disorder
Cannistraro, P. A., Makris, N., Howard, J. D., Wedig, M. M., Hodge, S. M., Wilhelm, S., Kennedy, D. N., & Rauch, S. L. (2007) · Depression and Anxiety · doi:10.1002/da.20246 · Cited by 154 · see citing works
Diffusion tensor imaging in normal aging and neuropsychiatric disorders
Sullivan, E. V., & Pfefferbaum, A. (2003) · European Journal of Radiology · doi:10.1016/s0720-048x(02)00313-3 · Cited by 148 · see citing works
Gerlai, R. T., Pisacane, P. I., & Erickson, S. L. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00175-8 · Cited by 144 · see citing works
Scherer, S. S., Braun, P. E., Grinspan, J. B., Collarini, E. J., Wang, D.-Y., & Kamholz, J. A. (1994) · Neuron · doi:10.1016/0896-6273(94)90451-0 · Cited by 142 · see citing works
Benoit‐Marand, M., Jaber, M., & Gonon, F. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00155.x · Cited by 137 · see citing works
Self-citationA magnetic resonance spectroscopy investigation of obsessive–compulsive disorder and anxiety
Whiteside, S. P. H., Port, J. D., Deacon, B. J., & Abramowitz, J. S. (2006) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2005.12.006 · Cited by 133 · see citing works
Walterfang, M., Wood, S. J., Velakoulis, D., & Pantelis, C. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.02.001 · Cited by 131 · see citing works
Carter, C. J. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.05.023 · Cited by 126 · see citing works
Georgieva, L., Moskvina, V., Peirce, T., Norton, N., Bray, N. J., Jones, L., Holmans, P., MacGregor, S., Zammit, S., Wilkinson, J. C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603029103 · Cited by 125 · see citing works
Rimer, M., Barrett, D. W., Maldonado, M. A., Vock, V. M., & Gonzalez-Lima, F. (2005) · Neuroreport · doi:10.1097/00001756-200502280-00014 · Cited by 120 · see citing works
Prevalence and impact of comorbid anxiety and bipolar disorder.
Keller, M. B. (2006) · PubMed · Cited by 112 · see citing works
Anxiety disorders in schizophrenia
Braga, R. J., Petrides, G., & Figueira, I. L. D. V. (2004) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2004.07.009 · Cited by 112 · see citing works
Activity-dependent regulation of Neu differentiation factor/neuregulin expression in rat brain
Eilam, R., Pinkas‐Kramarski, R., Ratzkin, B. J., Segal, M., & Yarden, Y. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1888 · Cited by 107 · see citing works
Cocaine reward and MPTP toxicity: alteration by regional variant dopamine transporter overexpression
Donovan, D. M., Miner, L. L., Perry, M. P., Revay, R. S., Sharpe, L. G., Przedborski, S., Kostić, V., Philpot, R. M., Kirstein, C. L., Rothman, R. B., et al. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00235-1 · Cited by 94 · see citing works
Morphometric analysis of oligodendrocytes in the adult mouse frontal cortex
Murtie, J. C., Macklin, W. B., & Corfas, G. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21339 · Cited by 73 · see citing works
Self-citationBirth insult increases amphetamine-induced behavioral responses in the adult rat.
El-Khodor, B., & Boksa, P. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00194-8 · Cited by 66 · see citing works
Self-citationIdentification and Characterization of Early Glial Progenitors Using a Transgenic Selection Strategy
Chandross, K. J., Cohen, R. I., Paras, P., et al. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-02-00759.1999 · Cited by 58 · see citing works
Axonal Signals and Oligodendrocyte Differentiation
Bozzali, M., & Wrabetz, L. G. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000021242.12455.75 · Cited by 57 · see citing works
In vivo analysis of oligodendrocyte lineage development in postnatal FGF2 null mice
Murtie, J. C., Zhou, Y., Le, T. Q., & Armstrong, R. C. (2004) · Glia · doi:10.1002/glia.20142 · Cited by 51 · see citing works
Self-citationA novel family of ancient vertebrate odorant receptors
Berghard, A., & Dryer, L. (1998) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(19981115)37:3 · Cited by 50 · see citing works
Focus on Childhood and Adolescent Mental Health
DelBello, M. P. (2006) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v67n0101 · Cited by 45 · see citing works
Upregulation of erbB receptors in rat brain after middle cerebral arterial occlusion
Xu, Z., & Ford, B. D. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.11.039 · Cited by 43 · see citing works
Neuregulin expression after focal stroke in the rat
Parker, M. W., Chen, Y., Hallenbeck, J. M., et al. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)01126-6 · Cited by 34 · see citing works
Tan, S., Hermann, B., & Borrelli, E. (2003) · International review of neurobiology · doi:10.1016/s0074-7742(03)54005-3 · Cited by 32 · see citing works
The use of stereological counting methods to assess immediate early gene immunoreactivity
Mura, A., Murphy, C. A., Feldon, J., & Jongen‐Rêlo, A. L. (2004) · Brain Research · doi:10.1016/j.brainres.2004.02.054 · Cited by 24 · see citing works
Neurochemical changes in dopamine D1, D3 and D1/D3 receptor knockout mice
Wong, J. Y. F., Clifford, J. J., Massalas, J. S., et al. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01862-4 · Cited by 20 · see citing works
Zeng, B. ‐., Heales, S., Canevari, L., et al. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.08.022 · Cited by 19 · see citing works
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- [43]Keller MB. J Clin Psychiatry. 2006;67(Suppl 1):5–7. [PubMed] [Google Scholar]
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Fields, R. D. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.04.001 · Cited by 1,337 · see citing works
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Mei, L., & Xiong, W.-C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2392 · Cited by 1,030 · see citing works
A critical period for social experience-dependent oligodendrocyte maturation and myelination
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Chen, Y.-J. J., Johnson, M. A., Lieberman, M. D., Goodchild, R. E., Schobel, S., Lewandowski, N., Rosoklija, G., Liu, R.-C., Gingrich, J. A., Small, S., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1815-08.2008 · Cited by 188 · see citing works
Self-citationGiera, S., Luo, R., Ying, Y., Ackerman, S. D., Jeong, S.-J., Stoveken, H. M., Folts, C. J., Welsh, C. A., Tall, G. G., Stevens, B., et al. (2018) · eLife · doi:10.7554/elife.33385 · Cited by 145 · see citing works
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- Authors
- Roy, K., Murtie, J. C., El-Khodor, B. F., Edgar, N., Sardi, S. P., Hooks, B. M., Benoit-Marand, M., Chen, C., Moore, H., O'Donnell, P., Brunner, D., & Corfas, G.
- Affiliations
- Boston Children's Hospital (US)
- PsychoGenics, Inc., Tarrytown, NY 10591;
- Psychogenics (United States) (US)
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201; and
- Columbia University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-05-08
- Volume
- 104
- Issue
- 19
- Pages
- 8131-8136
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1876583
- OpenAlex
- W2025008591
- Cited by
- 319
- References
- 54
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 12 · 2023: 9 · 2022: 12 · 2021: 10 · 2020: 11 · 2019: 14 · 2018: 11 · 2017: 15 · 2016: 8 · 2015: 19 · 2014: 13 · 2013: 21 · 2012: 23
- FWCI
- 21.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institutes of Health (5p50mh066171-05)
- National Institute of Mental Health (R43MH070264, P50 MH66171, P50-MH066171, R01MH060131)
- National Institute of Neurological Disorders and Stroke (F31NS048630, NS7473, R01NS035884, T32NS007473)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- ErbB signaling, oligodendrocytes, neuregulin-1, ErbB4, myelination, myelin thickness, axonal conduction velocity, dopaminergic activity, dopamine receptors, dopamine transporter, neuropsychiatric disorders, schizophrenia, bipolar disorder, transgenic mice
- MeSH terms
- Amphetamine, Animals, Anxiety, Mental Disorders, Dopamine, Mice, Transgenic, Motor Activity, Myelin Sheath, Nerve Tissue Proteins, Neural Conduction, Oligodendroglia, Phosphoric Diester Hydrolases, Promoter Regions, Genetic, Social Behavior, Signal Transduction, Neuregulin-1, Mice, Cyclic Nucleotide Phosphodiesterases, Type 1, ErbB Receptors, Receptor, ErbB-4
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