4 research outputs found

    Neuregulin 1 Type III/ErbB Signaling Is Crucial for Schwann Cell Colonization of Sympathetic Axons

    Get PDF
    Analysis of Schwann cell (SC) development has been hampered by the lack of growing axons in many commonly used in vitro assays. As a consequence, the molecular signals and cellular dynamics of SC development along peripheral axons are still only poorly understood. Here we use a superior cervical ganglion (SCG) explant assay, in which axons elongate after treatment with nerve growth factor (NGF). Migration as well as proliferation and apoptosis of endogenous SCG-derived SCs along sympathetic axons were studied in these cultures using pharmacological interference and time-lapse imaging. Inhibition of ErbB receptor tyrosine kinases leads to reduced SC proliferation, increased apoptosis and thereby severely interfered with SC migration to distal axonal sections and colonization of axons. Furthermore we demonstrate that SC colonization of axons is also strongly impaired in a specific null mutant of an ErbB receptor ligand, Neuregulin 1 (NRG1) type III. Taken together, using a novel SC development assay, we demonstrate that NRG1 type III serves as a critical axonal signal for glial ErbB receptors that drives SC development along sympathetic axons

    Dysregulated Expression Of Neuregulin-1 By Cortical Pyramidal Neurons Disrupts Synaptic Plasticity

    No full text
    Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated ordecreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions invivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an "optimal" level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect. © 2014 The Authors.8411301145Agarwal, A., Dibaj, P., Kassmann, C.M., Goebbels, S., Nave, K.A., Schwab, M.H., Invivo imaging and noninvasive ablation of pyramidal neurons in adult NEX-CreERT2 mice (2012) Cereb. Cortex, 22, pp. 1473-1486Ayalew, M., Le-Niculescu, H., Levey, D.F., Jain, N., Changala, B., Patel, S.D., Winiger, E., Amdur, R., Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction (2012) Mol. Psychiatry, 17, pp. 887-905Berning, S., Willig, K.I., Steffens, H., Dibaj, P., Hell, S.W., Nanoscopy in a living mouse brain (2012) Science, 335, p. 551Bertram, I., Bernstein, H.G., Lendeckel, U., Bukowska, A., Dobrowolny, H., Keilhoff, G., Kanakis, D., Bogerts, B., Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression (2007) Ann. N Y Acad. Sci., 1096, pp. 147-156Brinkmann, B.G., Agarwal, A., Sereda, M.W., Garratt, A.N., Müller, T., Wende, H., Stassart, R.M., Velanac, V., Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system (2008) Neuron, 59, pp. 581-595Brzózka, M.M., Radyushkin, K., Wichert, S.P., Ehrenreich, H., Rossner, M.J., Cognitive and sensorimotor gating impairments in transgenic mice overexpressing the schizophrenia susceptibility gene Tcf4 in the brain (2010) Biol. Psychiatry, 68, pp. 33-40Cahill, M.E., Remmers, C., Jones, K.A., Xie, Z., Sweet, R.A., Penzes, P., Neuregulin1 signaling promotes dendritic spine growth through kalirin (2013) J.Neurochem., 126, pp. 625-635Carraway, K.L., Weber, J.L., Unger, M.J., Ledesma, J., Yu, N., Gassmann, M., Lai, C., Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases (1997) Nature, 387, pp. 512-516Chen, Y.J., Johnson, M.A., Lieberman, M.D., Goodchild, R.E., Schobel, S., Lewandowski, N., Rosoklija, G., Small, S., Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components (2008) J.Neurosci., 28, pp. 6872-6883Chen, Y.J., Zhang, M., Yin, D.M., Wen, L., Ting, A., Wang, P., Lu, Y.S., Wu, C.Y., ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation (2010) Proc. Natl. Acad. Sci. USA, 107, pp. 21818-21823Cooper, M.A., Koleske, A.J., Ablation of ErbB4 from excitatory neurons leads to reduced dendritic spine density in mouse prefrontal cortex (2014) J.Comp. Neurol., 522, pp. 3351-3362Deakin, I.H., Nissen, W., Law, A.J., Lane, T., Kanso, R., Schwab, M.H., Nave, K.A., Harrison, P.J., Transgenic overexpression of the type I isoform of neuregulin 1 affects working memory and hippocampal oscillations but not long-term potentiation (2012) Cereb. Cortex, 22, pp. 1520-1529Del Pino, I., García-Frigola, C., Dehorter, N., Brotons-Mas, J.R., Alvarez-Salvado, E., Martínez de Lagrán, M., Ciceri, G., Dierssen, M., Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes (2013) Neuron, 79, pp. 1152-1168Deutsch, S.I., Rosse, R.B., Mastropaolo, J., Behavioral approaches to the functional assessment of NMDA-mediated neural transmission in intact mice (1997) Clin. Neuropharmacol., 20, pp. 375-384Dodd, P.R., Hardy, J.A., Oakley, A.E., Edwardson, J.A., Perry, E.K., Delaunoy, J.P., A rapid method for preparing synaptosomes: comparison, with alternative procedures (1981) Brain Res., 226, pp. 107-118Falls, D.L., Neuregulins: functions, forms, and signaling strategies (2003) Exp. Cell Res., 284, pp. 14-30Fazzari, P., Paternain, A.V., Valiente, M., Pla, R., Luján, R., Lloyd, K., Lerma, J., Rico, B., Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling (2010) Nature, 464, pp. 1376-1380Flames, N., Long, J.E., Garratt, A.N., Fischer, T.M., Gassmann, M., Birchmeier, C., Lai, C., Marín, O., Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1 (2004) Neuron, 44, pp. 251-261Gorski, J.A., Talley, T., Qiu, M., Puelles, L., Rubenstein, J.L., Jones, K.R., Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage (2002) J.Neurosci., 22, pp. 6309-6314Gu, Z., Jiang, Q., Fu, A.K., Ip, N.Y., Yan, Z., Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex (2005) J.Neurosci., 25, pp. 4974-4984Hahn, C.G., Wang, H.Y., Cho, D.S., Talbot, K., Gur, R.E., Berrettini, W.H., Bakshi, K., Siegel, S.J., Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia (2006) Nat. Med., 12, pp. 824-828Hering, H., Sheng, M., Dendritic spines: structure, dynamics and regulation (2001) Nat. Rev. Neurosci., 2, pp. 880-888Hirrlinger, P.G., Scheller, A., Braun, C., Quintela-Schneider, M., Fuss, B., Hirrlinger, J., Kirchhoff, F., Expression of reef coral fluorescent proteins in the central nervous system of transgenic mice (2005) Mol. Cell. Neurosci., 30, pp. 291-303Huang, Y.Z., Won, S., Ali, D.W., Wang, Q., Tanowitz, M., Du, Q.S., Pelkey, K.A., Mei, L., Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses (2000) Neuron, 26, pp. 443-455Jiang, L., Emmetsberger, J., Talmage, D.A., Role, L.W., Type III neuregulin 1 is required for multiple forms of excitatory synaptic plasticity of mouse cortico-amygdala circuits (2013) J.Neurosci., 33, pp. 9655-9666Kwon, O.B., Longart, M., Vullhorst, D., Hoffman, D.A., Buonanno, A., Neuregulin-1 reverses long-term potentiation at CA1 hippocampal synapses (2005) J.Neurosci., 25, pp. 9378-9383Law, A.J., Lipska, B.K., Weickert, C.S., Hyde, T.M., Straub, R.E., Hashimoto, R., Harrison, P.J., Weinberger, D.R., Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5' SNPs associated with the disease (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 6747-6752Li, L., Cleary, S., Mandarano, M.A., Long, W., Birchmeier, C., Jones, F.E., The breast proto-oncogene, HRGalpha regulates epithelial proliferation and lobuloalveolar development in the mouse mammary gland (2002) Oncogene, 21, pp. 4900-4907Li, D., Collier, D.A., He, L., Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia (2006) Hum. Mol. Genet., 15, pp. 1995-2002Li, K.X., Lu, Y.M., Xu, Z.H., Zhang, J., Zhu, J.M., Zhang, J.M., Cao, S.X., Luo, J.H., Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy (2012) Nat. Neurosci., 15, pp. 267-273Liu, X., Bates, R., Yin, D.M., Shen, C., Wang, F., Su, N., Kirov, S.A., Mei, L., Specific regulation of NRG1 isoform expression by neuronal activity (2011) J.Neurosci., 31, pp. 8491-8501Martins-de-Souza, D., Menezes de Oliveira, B., dos Santos Farias, A., Horiuchi, R.S., Crepaldi Domingues, C., de Paula, E., Marangoni, S., Camillo Novello, J., The use of ASB-14 in combination with CHAPS is the best for solubilization of human brain proteins for two-dimensional gel electrophoresis (2007) Brief. Funct. Genomic Proteomic, 6, pp. 70-75Mata, I., Perez-Iglesias, R., Roiz-Santiañez, R., Tordesillas-Gutierrez, D., Gonzalez-Mandly, A., Vazquez-Barquero, J.L., Crespo-Facorro, B., A neuregulin 1 variant is associated with increased lateral ventricle volume in patients with first-episode schizophrenia (2009) Biol. Psychiatry, 65, pp. 535-540Meyer, D., Birchmeier, C., Multiple essential functions of neuregulin in development (1995) Nature, 378, pp. 386-390Meyer, A.H., Katona, I., Blatow, M., Rozov, A., Monyer, H., Invivo labeling of parvalbumin-positive interneurons and analysis of electrical coupling in identified neurons (2002) J.Neurosci., 22, pp. 7055-7064Michailov, G.V., Sereda, M.W., Brinkmann, B.G., Fischer, T.M., Haug, B., Birchmeier, C., Role, L., Nave, K.A., Axonal neuregulin-1 regulates myelin sheath thickness (2004) Science, 304, pp. 700-703Miles, R., Tóth, K., Gulyás, A.I., Hájos, N., Freund, T.F., Differences between somatic and dendritic inhibition in the hippocampus (1996) Neuron, 16, pp. 815-823Minichiello, L., Korte, M., Wolfer, D., Kühn, R., Unsicker, K., Cestari, V., Rossi-Arnaud, C., Klein, R., Essential role for TrkB receptors in hippocampus-mediated learning (1999) Neuron, 24, pp. 401-414Mizoguchi, A., Ueda, T., Ikeda, K., Shiku, H., Mizoguti, H., Takai, Y., Localization and subcellular distribution of cellular ras gene products in rat brain (1989) Brain Res. Mol. Brain Res., 5, pp. 31-44Mizuno, K., Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation (2013) Cell. Signal., 25, pp. 457-469Natt, O., Watanabe, T., Boretius, S., Radulovic, J., Frahm, J., Michaelis, T., High-resolution 3D MRI of mouse brain reveals small cerebral structures invivo (2002) J.Neurosci. Methods, 120, pp. 203-209Nave, K.A., Salzer, J.L., Axonal regulation of myelination by neuregulin 1 (2006) Curr. Opin. Neurobiol., 16, pp. 492-500Neddens, J., Buonanno, A., Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice (2010) Hippocampus, 20, pp. 724-744Ozaki, M., Sasner, M., Yano, R., Lu, H.S., Buonanno, A., Neuregulin-beta induces expression of an NMDA-receptor subunit (1997) Nature, 390, pp. 691-694Penzes, P., Cahill, M.E., Jones, K.A., VanLeeuwen, J.E., Woolfrey, K.M., Dendritic spine pathology in neuropsychiatric disorders (2011) Nat. Neurosci., 14, pp. 285-293Pitcher, G.M., Beggs, S., Woo, R.S., Mei, L., Salter, M.W., ErbB4 is a suppressor of long-term potentiation in the adult hippocampus (2008) Neuroreport, 19, pp. 139-143Pitcher, G.M., Kalia, L.V., Ng, D., Goodfellow, N.M., Yee, K.T., Lambe, E.K., Salter, M.W., Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors (2011) Nat. Med., 17, pp. 470-478Role, L.W., Talmage, D.A., Neurobiology: new order for thought disorders (2007) Nature, 448, pp. 263-265Shamir, A., Kwon, O.B., Karavanova, I., Vullhorst, D., Leiva-Salcedo, E., Janssen, M.J., Buonanno, A., The importance of the NRG-1/ErbB4 pathway for synaptic plasticity and behaviors associated with psychiatric disorders (2012) J.Neurosci., 32, pp. 2988-2997Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Chou, T.T., Neuregulin 1 and susceptibility to schizophrenia (2002) Am. J. Hum. Genet., 71, pp. 877-892Tan, G.H., Liu, Y.Y., Hu, X.L., Yin, D.M., Mei, L., Xiong, Z.Q., Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons (2012) Nat. Neurosci., 15, pp. 258-266Ting, A.K., Chen, Y., Wen, L., Yin, D.M., Shen, C., Tao, Y., Liu, X., Mei, L., Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons (2011) J.Neurosci., 31, pp. 15-25Trommald, M., Hulleberg, G., Andersen, P., Long-term potentiation is associated with new excitatory spine synapses on rat dentate granule cells (1996) Learn. Mem., 3, pp. 218-228Uhlhaas, P.J., Singer, W., Abnormal neural oscillations and synchrony in schizophrenia (2010) Nat. Rev. Neurosci., 11, pp. 100-113Velanac, V., Unterbarnscheidt, T., Hinrichs, W., Gummert, M.N., Fischer, T.M., Rossner, M.J., Trimarco, A., Willem, M., Bace1 processing of NRG1 type III produces a myelin-inducing signal but is not essential for the stimulation of myelination (2012) Glia, 60, pp. 203-217Wang, J.Y., Frenzel, K.E., Wen, D., Falls, D.L., Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition (1998) J.Biol. Chem., 273, pp. 20525-20534Weickert, C.S., Tiwari, Y., Schofield, P.R., Mowry, B.J., Fullerton, J.M., Schizophrenia-associated HapICE haplotype is associated with increased NRG1 type III expression and high nucleotide diversity (2012) Transl. Psychiatr., 2, pp. e104Wen, L., Lu, Y.S., Zhu, X.H., Li, X.M., Woo, R.S., Chen, Y.J., Yin, D.M., Vazdarjanova, A., Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons (2010) Proc. Natl. Acad. Sci. USA, 107, pp. 1211-1216Woo, R.S., Li, X.M., Tao, Y., Carpenter-Hyland, E., Huang, Y.Z., Weber, J., Neiswender, H., Gassmann, M., Neuregulin-1 enhances depolarization-induced GABA release (2007) Neuron, 54, pp. 599-610Yin, D.M., Chen, Y.J., Lu, Y.S., Bean, J.C., Sathyamurthy, A., Shen, C., Liu, X., Mei, L., Reversal of behavioral deficits and synaptic dysfunction in mice overexpressing neuregulin 1 (2013) Neuron, 78, pp. 644-657Yin, D.M., Sun, X.D., Bean, J.C., Lin, T.W., Sathyamurthy, A., Xiong, W.C., Gao, T.M., Mei, L., Regulation of spine formation by ErbB4 in PV-positive interneurons (2013) J.Neurosci., 33, pp. 19295-19303Zhong, C., Du, C., Hancock, M., Mertz, M., Talmage, D.A., Role, L.W., Presynaptic type III neuregulin 1 is required for sustained enhancement of hippocampal transmission by nicotine and for axonal targeting of alpha7 nicotinic acetylcholine receptors (2008) J.Neurosci., 28, pp. 9111-911
    corecore