Table Info

Table 1.

NRG and neurological diseases

Disease	Aging	AD	PD	BT	SZ
Main hallmarks	Gradual loss of cognitive functions. Developmental abnormalities in cortical circuitry	Neuritic plaques. Neurofibrillary tangles. Accumulation beta-amyloid peptide (Aβ)	Degeneration of DAergic neurons. Deposition of α-synuclein	A brain injury that disrupts normal cellular and tissue function (b)	Chronic mental illness presents highly heritable genetic factors. Likely a consequence of neurodevelopmental disorders
Role of NRG	Neuroprotection, related to maximum lifespan in model systems	Neuroprotection. Decrement of Aβ peptide. Regulation of α-7 nAChR	Protection of DAergic neurons, elevation of DA levels (a)	Neuroprotection. Anti-inflammatory responses. Anti-apoptotic. Beneficial effects on endothelial cells and BBB permeability	Genetic association (NRG and ErbB). High levels of NRG1 contribute to hippocampal synaptic plasticity dysfunction (c)
Main affected areas	Cortex, PFC	Hippocampus and cerebral cortex	Substantia nigra, hypothalamus	Any area	Cerebral cortex, PFC, hippocampus

Summary of the neurological diseases discussed in the review, showing their main features and how NRG is involved in those diseases. (a) In PD, ErbB4 is overexpressed and occurs with an excessive release of NRG; (b) BT: traumatic brain injury, stroke, etc.; (c) SZ: NRG1 concentration in serum is modulated by antipsychotic treatments and could be a therapeutic target. BBB: blood-brain barrier; nAChR: nicotinic ACh-R; BT: brain trauma; PD: Parkinson’s disease

Declarations

Author contributions

ML designed the outline of the manuscript, wrote the abstract, part of sections 1, 2, and 3, contributed to Table 1, wrote the conclusions, and corrected the grammar. CC helped with the general outline, wrote section 4, and contributed to Table 1. MG wrote section 5, performed the main design of the Figures and significantly contributed to the final Figures. MEG wrote part of section 1, significantly contributed to the design of the final Figures, formatted the citations and references, and helped significantly in the revision of the grammar. JCM wrote part of section 1, revised the entire manuscript, and corrected the grammar. All authors contributed to the design and development of the different sections of this review and gave insights into the final design of the Figures. All authors read and revised the final manuscript.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

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Availability of data and materials

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Funding

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Copyright

References

Douglas L. Falls. Neuregulins: functions, forms, and signaling strategies. In: In: Graham Carpenter, editor. The EGF receptor family. Burlington: Academic Press; 2003. pp. 15–31. [DOI] [PubMed]

Mei L, Xiong WC. Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci. 2008;9:437–52. [DOI] [PubMed] [PMC]

Ledonne A, Mercuri NB. Insights on the functional interaction between group 1 metabotropic glutamate receptors (mGluRI) and ErbB receptors. Int J Mol Sci. 2020;21:7913. [DOI] [PubMed] [PMC]

Kao WT, Wang Y, Kleinman JE, Lipska BK, Hyde TM, Weinberger DR, et al. Common genetic variation in neuregulin 3 (NRG3) influences risk for schizophrenia and impacts NRG3 expression in human brain. Proc Natl Acad Sci U S A. 2010;107:15619–24. [DOI] [PubMed] [PMC]

Mei L, Nave KA. Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron. 2014;83:27–49. [DOI] [PubMed] [PMC]

Brown DJ, Lin B, Holguin B. Expression of neuregulin 1, a member of the epidermal growth factor family, is expressed as multiple splice variants in the adult human cornea. Invest Ophthalmol Vis Sci. 2004;45:3021–9. [DOI] [PubMed]

Steinthorsdottir V, Stefansson H, Ghosh S, Birgisdottir B, Bjornsdottir S, Fasquel AC, et al. Multiple novel transcription initiation sites for NRG1. Gene. 2004;342:97–105. [DOI] [PubMed]

Tan W, Wang Y, Gold B, Chen J, Dean M, Harrison PJ, et al. Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia. J Biol Chem. 2007;282:24343–51. [DOI] [PubMed]

Liu X, Bates R, Yin DM, Shen C, Wang F, Su N, et al. Specific regulation of NRG1 isoform expression by neuronal activity. J Neurosci. 2011;31:8491–501. [DOI] [PubMed] [PMC]

10.

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;276:38068–75. [DOI] [PubMed]

11.

Law AJ, Shannon Weickert C, Hyde TM, Kleinman JE, Harrison PJ. Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain. Neuroscience. 2004;127:125–36. [DOI] [PubMed]

12.

Chang H, Riese DJ 2nd, Gilbert W, Stern DF, McMahan UJ. Ligands for ErbB-family receptors encoded by a neuregulin-like gene. Nature. 1997;387:509–12. [DOI] [PubMed]

13.

Carraway KL 3rd, Weber JL, Unger MJ, Ledesma J, Yu N, Gassmann M, et al. Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. Nature. 1997;387:512–6. [DOI] [PubMed]

14.

Busfield SJ, Michnick DA, Chickering TW, Revett TL, Ma J, Woolf EA, et al. Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus. Mol Cell Biol. 1997;17:4007–14. [DOI] [PubMed] [PMC]

15.

Longart M, Liu Y, Karavanova I, Buonanno A. Neuregulin-2 is developmentally regulated and targeted to dendrites of central neurons. J Comp Neurol. 2004;472:156–72. [DOI] [PubMed]

16.

Yan L, Shamir A, Skirzewski M, Leiva-Salcedo E, Kwon OB, Karavanova I, et al. Neuregulin-2 ablation results in dopamine dysregulation and severe behavioral phenotypes relevant to psychiatric disorders. Mol Psychiatry. 2018;23:1233–43. [DOI] [PubMed] [PMC]

17.

Carteron C, Ferrer-Montiel A, Cabedo H. Characterization of a neural-specific splicing form of the human neuregulin 3 gene involved in oligodendrocyte survival. J Cell Sci. 2006;119:898–909. [DOI] [PubMed]

18.

Paterson C, Wang Y, Hyde TM, Weinberger DR, Kleinman JE, Law AJ. Temporal, diagnostic, and tissue-specific regulation of NRG3 isoform expression in human brain development and affective disorders. Am J Psychiatry. 2017;174:256–65. [DOI] [PubMed] [PMC]

19.

Zeledón M, Eckart N, Taub M, Vernon H, Szymanksi M, Wang R, et al. Identification and functional studies of regulatory variants responsible for the association of NRG3 with a delusion phenotype in schizophrenia. Mol Neuropsychiatry. 2015;1:36–46. [DOI] [PubMed] [PMC]

20.

Ledonne A, Mercuri NB. On the modulatory roles of neuregulins/ErbB signaling on synaptic plasticity. Int J Mol Sci. 2020;21:275. [DOI] [PubMed] [PMC]

21.

Zhang D, Sliwkowski MX, Mark M, Frantz G, Akita R, Sun Y, et al. Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4. Proc Natl Acad Sci U S A. 1997;94:9562–7. [DOI] [PubMed] [PMC]

22.

Harari D, Tzahar E, Romano J, Shelly M, Pierce JH, Andrews GC, et al. Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase. Oncogene. 1999;18:2681–9. [DOI] [PubMed]

23.

Hayes NV, Gullick WJ. The neuregulin family of genes and their multiple splice variants in breast cancer. J Mammary Gland Biol Neoplasia. 2008;13:205–14. [DOI] [PubMed]

24.

Rosell M, Kaforou M, Frontini A, Okolo A, Chan YW, Nikolopoulou E, et al. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol Endocrinol Metab. 2014;306:E945–64. [DOI] [PubMed] [PMC]

25.

Paramo B, Wyatt S, Davies AM. An essential role for neuregulin-4 in the growth and elaboration of developing neocortical pyramidal dendrites. Exp Neurol. 2018;302:85–92. [DOI] [PubMed] [PMC]

26.

Uchida T, Wada K, Akamatsu T, Yonezawa M, Noguchi H, Mizoguchi A, et al. A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells. Biochem Biophys Res Commun. 1999;266:593–602. [DOI] [PubMed]

27.

Kanemoto N, Horie M, Omori K, Nishino N, Kondo M, Noguchi K, et al. Expression of TMEFF1 mRNA in the mouse central nervous system: precise examination and comparative studies of TMEFF1 and TMEFF2. Brain Res Mol Brain Res. 2001;86:48–55. [DOI] [PubMed]

28.

Kinugasa Y, Ishiguro H, Tokita Y, Oohira A, Ohmoto H, Higashiyama S. Neuroglycan C, a novel member of the neuregulin family. Biochem Biophys Res Commun. 2004;321:1045–9. [DOI] [PubMed]

29.

Aono S, Tokita Y, Yasuda Y, Hirano K, Yamauchi S, Shuo T, et al. Expression and identification of a new splice variant of neuroglycan C, a transmembrane chondroitin sulfate proteoglycan, in the human brain. J Neurosci Res. 2006;83:110–8. [DOI] [PubMed]

30.

Barros CS, Calabrese B, Chamero P, Roberts AJ, Korzus E, Lloyd K, et al. Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system. Proc Natl Acad Sci U S A. 2009;106:4507–12. [DOI] [PubMed] [PMC]

31.

Ting AK, Chen Y, Wen L, Yin DM, Shen C, Tao Y, et al. Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons. J Neurosci. 2011;31:15–25. [DOI] [PubMed] [PMC]

32.

Fazzari P, Paternain AV, Valiente M, Pla R, Luján R, Lloyd K, et al. Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature. 2010;464:1376–80. [DOI] [PubMed]

33.

Ryu J, Hong BH, Kim YJ, Yang EJ, Choi M, Kim H, et al. Neuregulin-1 attenuates cognitive function impairments in a transgenic mouse model of Alzheimer’s disease. Cell Death Dis. 2016;7:e2117. [DOI] [PubMed] [PMC]

34.

Chen P, Jing H, Xiong M, Zhang Q, Lin D, Ren D, et al. Spine impairment in mice high-expressing neuregulin 1 due to LIMK1 activation. Cell Death Dis. 2021;12:403. [DOI] [PubMed] [PMC]

35.

Wang JY, Miller SJ, Falls DL. The N-terminal region of neuregulin isoforms determines the accumulation of cell surface and released neuregulin ectodomain. J Biol Chem. 2001;276:2841–51. [DOI] [PubMed]

36.

Garratt AN, Britsch S, Birchmeier C. Neuregulin, a factor with many functions in the life of a schwann cell. Bioessays. 2000;22:987–96. [DOI] [PubMed]

37.

Nave KA, Salzer JL. Axonal regulation of myelination by neuregulin 1. Curr Opin Neurobiol. 2006;16:492–500. [DOI] [PubMed]

38.

Vullhorst D, Ahmad T, Karavanova I, Keating C, Buonanno A. Structural similarities between neuregulin 1-3 isoforms determine their subcellular distribution and signaling mode in central neurons. J Neurosci. 2017;37:5232–49. [DOI] [PubMed] [PMC]

39.

Gallart-Palau X, Tarabal O, Casanovas A, Sábado J, Correa FJ, Hereu M, et al. Neuregulin-1 is concentrated in the postsynaptic subsurface cistern of C-bouton inputs to α-motoneurons and altered during motoneuron diseases. FASEB J. 2014;28:3618–32. [DOI] [PubMed]

40.

Garcia RA, Vasudevan K, Buonanno A. The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses. Proc Natl Acad Sci U S A. 2000;97:3596–601. [DOI] [PubMed] [PMC]

41.

Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS, et al. Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses. Neuron. 2000;26:443–55. [DOI] [PubMed]

42.

Vullhorst D, Mitchell RM, Keating C, Roychowdhury S, Karavanova I, Tao-Cheng JH, et al. A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling. Nat Commun. 2015;6:7222. [DOI] [PubMed] [PMC]

43.

Loeb JA, Fischbach GD. ARIA can be released from extracellular matrix through cleavage of a heparin-binding domain. J Cell Biol. 1995;130:127–35. [DOI] [PubMed] [PMC]

44.

Ribeiro LF, Verpoort B, de Wit J. Trafficking mechanisms of synaptogenic cell adhesion molecules. Mol Cell Neurosci. 2018;91:34–47. [DOI] [PubMed]

45.

Sampo B, Kaech S, Kunz S, Banker G. Two distinct mechanisms target membrane proteins to the axonal surface. Neuron. 2003;37:611–24. [DOI] [PubMed]

46.

Gumy LF, Hoogenraad CC. Local mechanisms regulating selective cargo entry and long-range trafficking in axons. Curr Opin Neurobiol. 2018;51:23–8. [DOI] [PubMed]

47.

Ribeiro LF, Verpoort B, Nys J, Vennekens KM, Wierda KD, de Wit J. SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function. PLoS Biol. 2019;17:e3000466. [DOI] [PubMed] [PMC]

48.

Del Pino I, Rico B, Marín O. Neural circuit dysfunction in mouse models of neurodevelopmental disorders. Curr Opin Neurobiol. 2018;48:174–82. [DOI] [PubMed]

49.

Vullhorst D, Neddens J, Karavanova I, Tricoire L, Petralia RS, McBain CJ, et al. Selective expression of ErbB4 in interneurons, but not pyramidal cells, of the rodent hippocampus. J Neurosci. 2009;29:12255–64. [DOI] [PubMed] [PMC]

50.

Del Pino I, Brotons-Mas JR, Marques-Smith A, Marighetto A, Frick A, Marín O, et al. Abnormal wiring of CCK⁺ basket cells disrupts spatial information coding. Nat Neurosci. 2017;20:784–92. [DOI] [PubMed] [PMC]

51.

Del Pino I, García-Frigola C, Dehorter N, Brotons-Mas JR, Alvarez-Salvado E, Martínez de Lagrán M, et al. Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes. Neuron. 2013;79:1152–68. [DOI] [PubMed]

52.

Yang JM, Zhang J, Chen XJ, Geng HY, Ye M, Spitzer NC, et al. Development of GABA circuitry of fast-spiking basket interneurons in the medial prefrontal cortex of erbb4-mutant mice. J Neurosci. 2013;33:19724–33. [DOI] [PubMed] [PMC]

53.

Hancock ML, Canetta SE, Role LW, Talmage DA. Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons. J Gen Physiol. 2008;131:i4. [DOI] [PubMed]

54.

Wolpowitz D, Mason TB, Dietrich P, Mendelsohn M, Talmage DA, Role LW. Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron. 2000;25:79–91. [DOI] [PubMed]

55.

Müller T, Braud S, Jüttner R, Voigt BC, Paulick K, Sheean ME, et al. Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons. EMBO J. 2018;37:e98858. [DOI] [PubMed] [PMC]

56.

Exposito-Alonso D, Osório C, Bernard C, Pascual-García S, Del Pino I, Marín O, et al. Subcellular sorting of neuregulins controls the assembly of excitatory-inhibitory cortical circuits. Elife. 2020;9:e57000. [DOI] [PubMed] [PMC]

57.

Buonanno A, Fischbach GD. Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol. 2001;11:287–96. [DOI] [PubMed]

58.

Buonanno A. The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits. Brain Res Bull. 2010;83:122–31. [DOI] [PubMed] [PMC]

59.

Chen Y, Hancock ML, Role LW, Talmage DA. Intramembranous valine linked to schizophrenia is required for neuregulin 1 regulation of the morphological development of cortical neurons. J Neurosci. 2010;30:9199–208. [DOI] [PubMed] [PMC]

60.

Shamir A, Kwon OB, Karavanova I, Vullhorst D, Leiva-Salcedo E, Janssen MJ, et al. The importance of the NRG-1/ErbB4 pathway for synaptic plasticity and behaviors associated with psychiatric disorders. J Neurosci. 2012;32:2988–97. [DOI] [PubMed] [PMC]

61.

Gu Y, Tran T, Murase S, Borrell A, Kirkwood A, Quinlan EM. Neuregulin-dependent regulation of fast-spiking interneuron excitability controls the timing of the critical period. J Neurosci. 2016;36:10285–95. [DOI] [PubMed] [PMC]

62.

Sun Y, Ikrar T, Davis MF, Gong N, Zheng X, Luo ZD, et al. Neuregulin-1/ErbB4 signaling regulates visual cortical plasticity. Neuron. 2016;92:160–73. [DOI] [PubMed] [PMC]

63.

Bjarnadottir M, Misner DL, Haverfield-Gross S, Bruun S, Helgason VG, Stefansson H, et al. Neuregulin1 (NRG1) signaling through Fyn modulates NMDA receptor phosphorylation: differential synaptic function in NRG1^+/– knock-outs compared with wild-type mice. J Neurosci. 2007;27:4519–29. [DOI] [PubMed] [PMC]

64.

Fu AK, Fu WY, Cheung J, Tsim KW, Ip FC, Wang JH, et al. Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction. Nat Neurosci. 2001;4:374–81. [DOI] [PubMed]

65.

Si J, Mei L. ERK MAP kinase activation is required for acetylcholine receptor inducing activity-induced increase in all five acetylcholine receptor subunit mRNAs as well as synapse-specific expression of acetylcholine receptor epsilon-transgene. Brain Res Mol Brain Res. 1999;67:18–27. [DOI]

66.

Hellyer NJ, Cheng K, Koland JG. ErbB3 (HER3) interaction with the p85 regulatory subunit of phosphoinositide 3-kinase. Biochem J. 1998;333(Pt 3):757–63. [DOI] [PubMed] [PMC]

67.

Lee HJ, Jung KM, Huang YZ, Bennett LB, Lee JS, Mei L, et al. Presenilin-dependent gamma-secretase-like intramembrane cleavage of ErbB4. J Biol Chem. 2002;277:6318–23. [DOI] [PubMed]

68.

Ni CY, Murphy MP, Golde TE, Carpenter G. γ-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science. 2001;294:2179–81. [DOI] [PubMed]

69.

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;127:185–97. [DOI] [PubMed]

70.

Bao J, Wolpowitz D, Role LW, Talmage DA. Back signaling by the Nrg-1 intracellular domain. J Cell Biol. 2003;161:1133–41. [DOI] [PubMed] [PMC]

71.

Bao J, Lin H, Ouyang Y, Lei D, Osman A, Kim TW, et al. Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nat Neurosci. 2004;7:1250–8. [DOI] [PubMed]

72.

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;283:32944–56. [DOI] [PubMed] [PMC]

73.

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;28:6872–83. [DOI] [PubMed] [PMC]

74.

Rahman-Enyart A, Lai C, Prieto AL. Neuregulins 1, 2, and 3 promote early neurite outgrowth in ErbB4-expressing cortical GABAergic interneurons. Mol Neurobiol. 2020;57:3568–88. [DOI] [PubMed]

75.

Vullhorst D, Buonanno A. NMDA receptors regulate neuregulin 2 binding to ER-PM junctions and ectodomain release by ADAM10 [corrected]. Mol Neurobiol. 2019;56:8345–63. Erratum in: Mol Neurobiol. 2020;57:585. [DOI] [PubMed]

76.

Calaora V, Rogister B, Bismuth K, Murray K, Brandt H, Leprince P, et al. Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. J Neurosci. 2001;21:4740–51. [DOI] [PubMed] [PMC]

77.

Schmucker J, Ader M, Brockschnieder D, Brodarac A, Bartsch U, Riethmacher D. erbB3 is dispensable for oligodendrocyte development in vitro and in vivo. Glia. 2003;44:67–75. [DOI] [PubMed]

78.

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;125:127–42. [DOI] [PubMed] [PMC]

79.

Okada M, Corfas G. Neuregulin1 downregulates postsynaptic GABA_a receptors at the hippocampal inhibitory synapse. Hippocampus. 2004;14:337–44. [DOI] [PubMed]

80.

Fazzari P, Snellinx A, Sabanov V, Ahmed T, Serneels L, Gartner A, et al. Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling. Elife. 2014;3:e02196. [DOI] [PubMed] [PMC]

81.

Li B, Woo RS, Mei L, Malinow R. The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity. Neuron. 2007;54:583–97. [DOI] [PubMed] [PMC]

82.

Brandon NJ, Sawa A. Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nat Rev Neurosci. 2011;12:707–22. [DOI] [PubMed] [PMC]

83.

El-Husseini AE, Schnell E, Chetkovich DM, Nicoll RA, Bredt DS. PSD-95 involvement in maturation of excitatory synapses. Science. 2000;290:1364–8. [DOI] [PubMed]

84.

Rio C, Rieff HI, Qi P, Khurana TS, Corfas G. Neuregulin and erbB receptors play a critical role in neuronal migration. Neuron. 1997;19:39–50. Erratum in: Neuron 1997;19:1349. [DOI] [PubMed]

85.

Gerecke KM, Wyss JM, Carroll SL. Neuregulin-1β induces neurite extension and arborization in cultured hippocampal neurons. Mol Cell Neurosci. 2004;27:379–93. [DOI] [PubMed]

86.

Murphy SP, Bielby-Clarke K. Neuregulin signaling in neurons depends on ErbB4 interaction with PSD-95. Brain Res. 2008;1207:32–5. [DOI] [PubMed]

87.

Zhong C, Akmentin W, Du C, Role LW, Talmage DA. Axonal type III Nrg1 controls glutamate synapse formation and GluA2 trafficking in hippocampal-accumbens connections. eNeuro. 2017;4:ENEURO.0232–16.2017. [DOI] [PubMed] [PMC]

88.

Lee KH, Lee H, Yang CH, Ko JS, Park CH, Woo RS, et al. Bidirectional signaling of neuregulin-2 mediates formation of GABAergic synapses and maturation of glutamatergic synapses in newborn granule cells of postnatal hippocampus. J Neurosci. 2015;35:16479–93. [DOI] [PubMed] [PMC]

89.

Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci. 2000;23:649–711. [DOI] [PubMed]

90.

Hunt DL, Castillo PE. Synaptic plasticity of NMDA receptors: mechanisms and functional implications. Curr Opin Neurobiol. 2012;22:496–508. [DOI] [PubMed] [PMC]

91.

He Y, Kulasiri D, Samarasinghe S. Modelling bidirectional modulations in synaptic plasticity: a biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD). J Theor Biol. 2016;403:159–77. [DOI] [PubMed]

92.

Bin Ibrahim MZ, Benoy A, Sajikumar S. Long-term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses. FEBS J. 2022;289:2176–201. [DOI] [PubMed]

93.

Citri A, Malenka RC. Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008;33:18–41. [DOI] [PubMed]

94.

Hölscher C, Anwyl R, Rowan MJ. Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can be depotentiated by stimulation on the negative phase in area CA1 in vivo. J Neurosci. 1997;17:6470–7. [DOI] [PubMed] [PMC]

95.

Fujikawa A, Chow JP, Shimizu H, Fukada M, Suzuki R, Noda M. Tyrosine phosphorylation of ErbB4 is enhanced by PSD95 and repressed by protein tyrosine phosphatase receptor type Z. J Biochem. 2007;142:343–50. [DOI] [PubMed]

96.

Chaudhury AR, Gerecke KM, Wyss JM, Morgan DG, Gordon MN, Carroll SL. Neuregulin-1 and erbB4 immunoreactivity is associated with neuritic plaques in Alzheimer disease brain and in a transgenic model of Alzheimer disease. J Neuropathol Exp Neurol. 2003;62:42–54. [DOI] [PubMed]

97.

Kwon OB, Longart M, Vullhorst D, Hoffman DA, Buonanno A. Neuregulin-1 reverses long-term potentiation at CA1 hippocampal synapses. J Neurosci. 2005;25:9378–83. [DOI] [PubMed] [PMC]

98.

Pitcher GM, Kalia LV, Ng D, Goodfellow NM, Yee KT, Lambe EK, et al. Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors. Nat Med. 2011;17:470–8. [DOI] [PubMed] [PMC]

99.

Awasthi A, Ramachandran B, Ahmed S, Benito E, Shinoda Y, Nitzan N, et al. Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting. Science. 2019;363:eaav1483. [DOI] [PubMed]

100.

Liu X, Gu QH, Duan K, Li Z. NMDA receptor-dependent LTD is required for consolidation but not acquisition of fear memory. J Neurosci. 2014;34:8741–8. [DOI] [PubMed] [PMC]

101.

Thiels E, Xie X, Yeckel MF, Barrionuevo G, Berger TW. NMDA receptor-dependent LTD in different subfields of hippocampus in vivo and in vitro. Hippocampus. 1996;6:43–51. [DOI] [PubMed]

102.

Dudek SM, Bear MF. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc Natl Acad Sci U S A. 1992;89:4363–7. [DOI] [PubMed] [PMC]

103.

Lanté F, Cavalier M, Cohen-Solal C, Guiramand J, Vignes M. Developmental switch from LTD to LTP in low frequency-induced plasticity. Hippocampus. 2006;16:981–9. [DOI] [PubMed]

104.

Buschler A, Goh JJ, Manahan-Vaughan D. Frequency dependency of NMDA receptor-dependent synaptic plasticity in the hippocampal CA1 region of freely behaving mice. Hippocampus. 2012;22:2238–48. [DOI] [PubMed]

105.

Shen H, Zhu H, Panja D, Gu Q, Li Z. Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling. Nat Commun. 2020;11:2979. [DOI] [PubMed] [PMC]

106.

Cao Q, Wei Y, Deng J, Li J, Huang Y, Li Y, et al. NRG1 accelerates the forgetting of fear memories and facilitates the induction of long-term depression in adult mice. Psychopharmacology (Berl). 2021;238:2535–42. [DOI] [PubMed]

107.

Connor SA, Wang YT. A place at the table: LTD as a mediator of memory genesis. Neuroscientist. 2016;22:359–71. [DOI] [PubMed]

108.

Sengupta T, Das R, Chattarji S. Chronic but not acute immobilization stress stably enhances hippocampal CA1 metabotropic glutamate receptor dependent long-term depression. Neurosci Lett. 2016;633:101–5. [DOI] [PubMed]

109.

Hu Z, Yu P, Zhang Y, Yang Y, Zhu M, Qin S, et al. Inhibition of the ISR abrogates mGluR5-dependent long-term depression and spatial memory deficits in a rat model of Alzheimer’s disease. Transl Psychiatry. 2022;12:96. [DOI] [PubMed] [PMC]

110.

Ménard C, Quirion R. Group 1 metabotropic glutamate receptor function and its regulation of learning and memory in the aging brain. Front Pharmacol. 2012;3:182. [DOI] [PubMed] [PMC]

111.

Huang CC, Yeh CM, Wu MY, Chang AY, Chan JY, Chan SH, et al. Cocaine withdrawal impairs metabotropic glutamate receptor-dependent long-term depression in the nucleus accumbens. J Neurosci. 2011;31:4194–203. [DOI] [PubMed] [PMC]

112.

Lee K, Vyas Y, Garner CC, Montgomery JM. Autism-associated Shank3 mutations alter mGluR expression and mGluR-dependent but not NMDA receptor-dependent long-term depression. Synapse. 2019;73:e22097. [DOI] [PubMed]

113.

World Health Organization. Neurological disorders: public health challenges. Switzerland: WHO Press; 2006.

114.

Schirinzi T, Canevelli M, Suppa A, Bologna M, Marsili L. The continuum between neurodegeneration, brain plasticity, and movement: a critical appraisal. Rev Neurosci. 2020;31:723–42. [DOI] [PubMed]

115.

Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW. Mapping cortical change across the human life span. Nat Neurosci. 2003;6:309–15. [DOI] [PubMed]

116.

Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. 2004;101:8174–9. [DOI] [PubMed] [PMC]

117.

Tau GZ, Peterson BS. Normal development of brain circuits. Neuropsychopharmacology. 2010;35:147–68. [DOI] [PubMed] [PMC]

118.

Paterson C, Law AJ. Transient overexposure of neuregulin 3 during early postnatal development impacts selective behaviors in adulthood. PLoS One. 2014;9:e104172. [DOI] [PubMed] [PMC]

119.

Loos M, Schetters D, Hoogeland M, Spijker S, de Vries TJ, Pattij T. Prefrontal cortical neuregulin-ErbB modulation of inhibitory control in rats. Eur J Pharmacol. 2016;781:157–63. [DOI] [PubMed]

120.

Wang H, Liu F, Chen W, Sun X, Cui W, Dong Z, et al. Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice. Proc Natl Acad Sci U S A. 2018;115:13105–10. [DOI] [PubMed] [PMC]

121.

Jiang Q, Chen S, Hu C, Huang P, Shen H, Zhao W. Neuregulin-1 (Nrg1) signaling has a preventive role and is altered in the frontal cortex under the pathological conditions of Alzheimer’s disease. Mol Med Rep. 2016;14:2614–24. [DOI] [PubMed] [PMC]

122.

Xu J, de Winter F, Farrokhi C, Rockenstein E, Mante M, Adame A, et al. Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model. Sci Rep. 2016;6:31692. [DOI] [PubMed] [PMC]

123.

Edrey YH, Casper D, Huchon D, Mele J, Gelfond JA, Kristan DM, et al. Sustained high levels of neuregulin-1 in the longest-lived rodents; a key determinant of rodent longevity. Aging Cell. 2012;11:213–22. [DOI] [PubMed] [PMC]

124.

Paterson C, Cumming B, Law AJ. Temporal dynamics of the neuregulin-ErbB network in the murine prefrontal cortex across the lifespan. Cereb Cortex. 2020;30:3325–39. [DOI] [PubMed] [PMC]

125.

Brennan AR, Arnsten AF. Neuronal mechanisms underlying attention deficit hyperactivity disorder: the influence of arousal on prefrontal cortical function. Ann N Y Acad Sci. 2008;1129:236–45. [DOI] [PubMed] [PMC]

126.

Schumann CM, Bloss CS, Barnes CC, Wideman GM, Carper RA, Akshoomoff N, et al. Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. J Neurosci. 2010;30:4419–27. [DOI] [PubMed] [PMC]

127.

Goedert M, Spillantini MG. A century of Alzheimer’s disease. Science. 2006;314:777–81. [DOI] [PubMed]

128.

Cespedes JC, Liu M, Harbuzariu A, Nti A, Onyekaba J, Cespedes HW, et al. Neuregulin in health and disease. Int J Brain Disord Treat. 2018;4:024. [DOI] [PubMed] [PMC]

129.

Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362:329–44. Erratum in: N Engl J Med. 2011;364:588. [DOI] [PubMed]

130.

Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056. [DOI] [PubMed]

131.

Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science. 2007;316:750–4. [DOI] [PubMed]

132.

Pankonin MS, Sohi J, Kamholz J, Loeb JA. Differential distribution of neuregulin in human brain and spinal fluid. Brain Res. 2009;1258:1–11. [DOI] [PubMed]

133.

Yang Z, Jiang Q, Chen SX, Hu CL, Shen HF, Huang PZ, et al. Differential changes in neuregulin-1 signaling in major brain regions in a lipopolysaccharide-induced neuroinflammation mouse model. Mol Med Rep. 2016;14:790–6. [DOI] [PubMed] [PMC]

134.

Yoo JY, Kim HB, Baik TK, Lee JH, Woo RS. Neuregulin 1/ErbB4/Akt signaling attenuates cytotoxicity mediated by the APP-CT31 fragment of amyloid precursor protein. Exp Mol Pathol. 2021;120:104622. [DOI] [PubMed]

135.

Harrison PJ, Law AJ. Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry. 2006;60:132–40. [DOI] [PubMed]

136.

Zhang H, Zhang L, Zhou D, Li H, Xu Y. ErbB4 mediates amyloid β-induced neurotoxicity through JNK/tau pathway activation: implications for Alzheimer’s disease. J Comp Neurol. 2021;529:3497–512. [DOI] [PubMed]

137.

Vrillon A, Mouton-Liger F, Martinet M, Cognat E, Hourregue C, Dumurgier J, et al. Plasma neuregulin 1 as a synaptic biomarker in Alzheimer’s disease: a discovery cohort study. Alzheimers Res Ther. 2022;14:71. [DOI] [PubMed] [PMC]

138.

Mouton-Liger F, Dumurgier J, Cognat E, Hourregue C, Zetterberg H, Vanderstichele H, et al. CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease. Alzheimers Res Ther. 2020;12:88. [DOI] [PubMed] [PMC]

139.

Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain. 2018;141:1917–33. [DOI] [PubMed] [PMC]

140.

Corfas G, Rosen KM, Aratake H, Krauss R, Fischbach GD. Differential expression of ARIA isoforms in the rat brain. Neuron. 1995;14:103–15. [DOI] [PubMed]

141.

Liu Y, Ford B, Mann MA, Fischbach GD. Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus. J Neurosci. 2001;21:5660–9. [DOI] [PubMed] [PMC]

142.

Kim YJ, Yoo JY, Kim OS, Kim HB, Ryu J, Kim HS, et al. Neuregulin 1 regulates amyloid precursor protein cell surface expression and non-amyloidogenic processing. J Pharmacol Sci. 2018;137:146–53. [DOI] [PubMed]

143.

Sun C, Jia N, Li R, Zhang Z, Zhong Y, Han K. miR-143-3p inhibition promotes neuronal survival in an Alzheimer’s disease cell model by targeting neuregulin-1. Folia Neuropathol. 2020;58:10–21. [DOI] [PubMed]

144.

Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013. [DOI] [PubMed]

145.

Caligiore D, Helmich RC, Hallett M, Moustafa AA, Timmermann L, Toni I, et al. Parkinson’s disease as a system-level disorder. NPJ Parkinsons Dis. 2016;2:16025. [DOI] [PubMed] [PMC]

146.

Zijlmans JC, Daniel SE, Hughes AJ, Révész T, Lees AJ. Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov Disord. 2004;19:630–40. [DOI] [PubMed]

147.

Carlsson T, Schindler FR, Höllerhage M, Depboylu C, Arias-Carrión O, Schnurrbusch S, et al. Systemic administration of neuregulin-1β₁ protects dopaminergic neurons in a mouse model of Parkinson’s disease. J Neurochem. 2011;117:1066–74. [DOI] [PubMed]

148.

Depboylu C, Rösler TW, de Andrade A, Oertel WH, Höglinger GU. Systemically administered neuregulin-1β1 rescues nigral dopaminergic neurons via the ErbB4 receptor tyrosine kinase in MPTP mouse models of Parkinson’s disease. J Neurochem. 2015;133:590–7. [DOI] [PubMed]

149.

Depboylu C, Höllerhage M, Schnurrbusch S, Brundin P, Oertel WH, Schrattenholz A, et al. Neuregulin-1 receptor tyrosine kinase ErbB4 is upregulated in midbrain dopaminergic neurons in Parkinson disease. Neurosci Lett. 2012;531:209–14. [DOI] [PubMed]

150.

Ledonne A, Nobili A, Latagliata EC, Cavallucci V, Guatteo E, Puglisi-Allegra S, et al. Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons. Mol Psychiatry. 2015;20:959–73. [DOI] [PubMed]

151.

Huang M, Xu L, Liu J, Huang P, Tan Y, Chen S. Cell-cell communication alterations via intercellular signaling pathways in substantia nigra of Parkinson’s disease. Front Aging Neurosci. 2022;14:828457. [DOI] [PubMed] [PMC]

152.

Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic brain injury: an overview of epidemiology, pathophysiology, and medical management. Med Clin North Am. 2020;104:213–38. [DOI] [PubMed]

153.

Galgano M, Toshkezi G, Qiu X, Russell T, Chin L, Zhao LR. Traumatic brain injury: current treatment strategies and future endeavors. Cell Transplant. 2017;26:1118–30. [DOI] [PubMed] [PMC]

154.

Yoo JY, Kim HB, Yoo SY, Yoo HI, Song DY, Baik TK, et al. Neuregulin 1/ErbB4 signaling attenuates neuronal cell damage under oxygen-glucose deprivation in primary hippocampal neurons. Anat Cell Biol. 2019;52:462–8. [DOI] [PubMed] [PMC]

155.

Xu C, Lv L, Zheng G, Li B, Gao L, Sun Y. Neuregulin1β1 protects oligodendrocyte progenitor cells from oxygen glucose deprivation injury induced apoptosis via ErbB4-dependent activation of PI3-kinase/Akt. Brain Res. 2012;1467:104–12. [DOI] [PubMed]

156.

Cui W, Tao J, Wang Z, Ren M, Zhang Y, Sun Y, et al. Neuregulin1beta1 antagonizes apoptosis via ErbB4-dependent activation of PI3-kinase/Akt in APP/PS1 transgenic mice. Neurochem Res. 2013;38:2237–46. [DOI] [PubMed]

157.

Simmons LJ, Surles-Zeigler MC, Li Y, Ford GD, Newman GD, Ford BD. Regulation of inflammatory responses by neuregulin-1 in brain ischemia and microglial cells in vitro involves the NF-kappa B pathway. J Neuroinflammation. 2016;13:237. [DOI] [PubMed] [PMC]

158.

Robinson HL, Tan Z, Santiago-Marrero I, Arzola EP, Dong TV, Xiong WC, et al. Neuregulin 1 and ErbB4 kinase actively regulate sharp wave ripples in the hippocampus. J Neurosci. 2022;42:390–404. [DOI] [PubMed] [PMC]

159.

Lok J, Zhao S, Leung W, Seo JH, Navaratna D, Wang X, et al. Neuregulin-1 effects on endothelial and blood-brain-barrier permeability after experimental injury. Transl Stroke Res. 2012;3 Suppl 1:119–24. [DOI] [PubMed] [PMC]

160.

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;71:877–92. [DOI] [PubMed] [PMC]

161.

Yang JZ, Si TM, Ruan Y, Ling YS, Han YH, Wang XL, et al. Association study of neuregulin 1 gene with schizophrenia. Mol Psychiatry. 2003;8:706–9. [DOI] [PubMed]

162.

Li D, Collier DA, He L. Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Hum Mol Genet. 2006;15:1995–2002. [DOI] [PubMed]

163.

Munafò MR, Thiselton DL, Clark TG, Flint J. Association of the NRG1 gene and schizophrenia: a meta-analysis. Mol Psychiatry. 2006;11:539–46. Erratum in: Mol Psychiatry. 2006;11:613. [DOI] [PubMed]

164.

Norton N, Moskvina V, Morris DW, Bray NJ, Zammit S, Williams NM, et al. Evidence that interaction between neuregulin 1 and its receptor erbB4 increases susceptibility to schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:96–101. [DOI] [PubMed]

165.

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;10:366–74. [DOI] [PubMed]

166.

Agim ZS, Esendal M, Briollais L, Uyan O, Meschian M, Martinez LA, et al. Discovery, validation and characterization of Erbb4 and Nrg1 haplotypes using data from three genome-wide association studies of schizophrenia. PLoS One. 2013;8:e53042. [DOI] [PubMed] [PMC]

167.

Athanasiu L, Mattingsdal M, Kähler AK, Brown A, Gustafsson O, Agartz I, et al. Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. J Psychiatr Res. 2010;44:748–53. [DOI] [PubMed] [PMC]

168.

Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe’er I, et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature. 2009;460:753–7. [DOI] [PubMed] [PMC]

169.

Sullivan PF, Lin D, Tzeng JY, van den Oord E, Perkins D, Stroup TS, et al. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol Psychiatry. 2008;13:570–84. Erratum in: Mol Psychiatry. 2009;14:1144. [DOI] [PubMed] [PMC]

170.

Bousman CA, Cropley V, Klauser P, Hess JL, Pereira A, Idrizi R, et al. Neuregulin-1 (NRG1) polymorphisms linked with psychosis transition are associated with enlarged lateral ventricles and white matter disruption in schizophrenia. Psychol Med. 2018;48:801–9. [DOI] [PubMed]

171.

Harrison PJ. Recent genetic findings in schizophrenia and their therapeutic relevance. J Psychopharmacol. 2015;29:85–96. [DOI] [PubMed] [PMC]

172.

Tosato S, Zanoni M, Bonetto C, Tozzi F, Francks C, Ira E, et al. No association between NRG1 and ErbB4 genes and psychopathological symptoms of schizophrenia. Neuromolecular Med. 2014;16:742–51. [DOI] [PubMed]

173.

Wang C, Aleksic B, Ozaki N. Glia-related genes and their contribution to schizophrenia. Psychiatry Clin Neurosci. 2015;69:448–61. [DOI] [PubMed]

174.

Walss-Bass C, Liu W, Lew DF, Villegas R, Montero P, Dassori A, et al. A novel missense mutation in the transmembrane domain of neuregulin 1 is associated with schizophrenia. Biol Psychiatry. 2006;60:548–53. [DOI] [PubMed]

175.

Skirzewski M, Karavanova I, Shamir A, Erben L, Garcia-Olivares J, Shin JH, et al. ErbB4 signaling in dopaminergic axonal projections increases extracellular dopamine levels and regulates spatial/working memory behaviors. Mol Psychiatry. 2018;23:2227–37. [DOI] [PubMed] [PMC]

176.

Gu Z, Jiang Q, Fu AK, Ip NY, Yan Z. Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex. J Neurosci. 2005;25:4974–84. [DOI] [PubMed] [PMC]

177.

Olaya JC, Heusner CL, Matsumoto M, Sinclair D, Kondo MA, Karl T, et al. Overexpression of neuregulin 1 type III confers hippocampal mRNA alterations and schizophrenia-like behaviors in mice. Schizophr Bull. 2018;44:865–75. [DOI] [PubMed] [PMC]

178.

Chesworth R, Rosa-Porto R, Yao S, Karl T. Sex-specific sensitivity to methamphetamine-induced schizophrenia-relevant behaviours in neuregulin 1 type III overexpressing mice. J Psychopharmacol. 2021;35:50–64. [DOI] [PubMed]

179.

Yamazaki Y, Sumikawa K. Nicotine-induced neuroplasticity counteracts the effect of schizophrenia-linked neuregulin 1 signaling on NMDAR function in the rat hippocampus. Neuropharmacology. 2017;113:386–95. [DOI] [PubMed] [PMC]

180.

Du H, Kwon IK, Kim J. Neuregulin-1 impairs the long-term depression of hippocampal inhibitory synapses by facilitating the degradation of endocannabinoid 2-AG. J Neurosci. 2013;33:15022–31. [DOI] [PubMed] [PMC]

181.

Mostaid MS, Lee TT, Chana G, Sundram S, Shannon Weickert C, Pantelis C, et al. Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients. Transl Psychiatry. 2017;7:1280. [DOI] [PubMed] [PMC]