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Neuregulin 1 and Schizophrenia

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Signaling pathways regulated by the interaction of neuregulin1 (NRG1) and ErbB family members are essential for the formation and proper functioning of virtually all organ systems. Dysregulation of NRG1/ErbB signaling can severely compromise health, contributing to cancer, neurodegenerative and neuropsychiatric disorders, cardiac failure, and compromised reproductive capacity. Moreover, genetic studies of human cohorts from Iceland to East Asia have identified and confirmed that polymorphisms within the Nrg1 gene are associated with susceptibility to schizophrenia.

Numerous genetic modeling studies in mice demonstrate that NRG1 signaling is an important player in the development of normal and pathognomonic features of neuronal connectivity. Recent studies have identified novel signaling mechanisms and revealed unexpected roles of NRG1 isoforms in both the developing and adult nervous system. Of specific pertinence to this review are recent findings linking deficits in neuronal NRG1 expression with perturbations of synaptic transmission, myelination, and the survival of particular sets of neurons and glia. Despite the recent deluge of reports linking the NRG1/ErbB interaction to fundamental aspects of neuronal function, the molecular mediators of this bidirectional signaling pathway remain unknown.

In the following pages, we will first review the evidence linking NRG1 with schizophrenia, and provide a general review of the neuregulin gene family. Then we will discuss more specifically the emerging role for neuregulins, particularly the Type III isoforms, in the formation and maintenance of peripheral and central synapses. We hope that this will provide a framework for probing how alterations in the normal function of NRG1/ErbB signaling contribute to the etiology of schizophrenia.

NRG nomenclature used for this chapter:

  •  Human gene name: NRG1 (italics)

  •  Mouse or other nonhuman gene name: Nrg1 (italics)

  •  Protein (all species): NRG1 (not in italics)

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Abbreviations

COS:

childhood-onset schizophrenia

EGF:

epidermal growth factor

MGE:

medial ganglionic eminence

NRG1 :

neuregulin1

SNPs:

single-nucleotide polymorphisms

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Acknowledgments

Work cited from the authors’ laboratories was supported by grants from the NIH (NS29071 and NS22061), NARSAD and a McKnight Brain Disorders Award.

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  1. Y.-J. J. Chen
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  2. L. W. Role
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  3. D. A. Talmage
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York, 10962, USA

    Daniel Javitt (Director) (Director)

  3. Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York, 10962, USA

    Joshua Kantrowitz

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Chen, YJ.J., Role, L.W., Talmage, D.A. (2009). Neuregulin 1 and Schizophrenia. In: Lajtha, A., Javitt, D., Kantrowitz, J. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30410-6_6

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