ArticleBiological psychiatry2014
Reversible overexpression of bace1-cleaved neuregulin-1 N-terminal fragment induces schizophrenia-like phenotypes in mice.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
- Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical disinhibition.Nature communications · 2021Article
- Neuregulin 1: an intriguing therapeutic target for neurodevelopmental disorders.Translational psychiatry · 2020Review
- Add-on spironolactone as antagonist of the NRG1-ERBB4 signaling pathway for the treatment of schizophrenia: Study design and methodology of a multicenter randomized, placebo-controlled trial.Contemporary clinical trials communications · 2020Article
- Activated CX3CL1/Smad2 Signals Prevent Neuronal Loss and Alzheimer's Tau Pathology-Mediated Cognitive Dysfunction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Sociability development in mice with cell-specific deletion of the NMDA receptor NR1 subunit gene.Genes, brain, and behavior · 2020Article
- Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy.Human molecular genetics · 2019Article
- Altered hippocampal gene expression and structure in transgenic mice overexpressing neuregulin 1 (Nrg1) type I.Translational psychiatry · 2018Article
- Overexpression of Neuregulin 1 Type III Confers Hippocampal mRNA Alterations and Schizophrenia-Like Behaviors in Mice.Schizophrenia bulletin · 2018Article
- A gender dimorphism in up-regulation of BACE1 gene expression in schizophrenia.Metabolic brain disease · 2018Article
- Non-cell-autonomous function of DR6 in Schwann cell proliferation.The EMBO journal · 2018Article
- Spironolactone is an antagonist of NRG1-ERBB4 signaling and schizophrenia-relevant endophenotypes in mice.EMBO molecular medicine · 2017Article
- Article
- Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.Molecular neurobiology · 2017Article
- Physiological Functions of the β-Site Amyloid Precursor Protein Cleaving Enzyme 1 and 2.Frontiers in molecular neuroscience · 2017Review
- BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia.Frontiers in molecular neuroscience · 2017Review
- Functions of the Alzheimer's Disease Protease BACE1 at the Synapse in the Central Nervous System.Journal of molecular neuroscience : MN · 2016Review
- Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Myelination-related genes are associated with decreased white matter integrity in schizophrenia.European journal of human genetics : EJHG · 2016Article
- Neurological dysfunctions associated with altered BACE1-dependent Neuregulin-1 signaling.Journal of neurochemistry · 2016Review
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4 authors at 1 institution in 1 country.
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Abstract
backgroundNeuregulin-1 (Nrg1) is a pleiotropic signaling molecule that regulates neural development, and mutation of Nrg1 is a risk factor for schizophrenia. Cleavage of type I β1 Nrg1 isoform by Bace1 releases a secreted N-terminal fragment (Nrg1-ntfβ), which can bind to a cognate ErbB receptor to activate the specific signaling cascade. This study aimed to determine whether increased expression of Nrg1 is beneficial for brain development and functions.
methodsWe generated transgenic mice overexpressing this fragment under the control of a tetracycline-inducible promoter and examined functional and behavioral changes in mice upon reversible expression of the transgene.
resultsIncreased expression of full-length Nrg1 in mouse neurons has been previously shown to enhance myelination in the central nervous system. Overexpressing Nrg1-ntfβ enhanced the expression of myelin proteins, consistent with the expected activation of the Nrg1 signaling pathway by Nrg1-ntfβ. Contrary to expectations, overexpressing Nrg1-ntfβ transgene caused schizophrenia-like behaviors in transgenic mice, and these abnormal behaviors were reversible if the expression of the Nrg1-ntfβ transgene was turned off. Our molecular assay suggests that protein levels of N-methyl-D-aspartate receptors are reduced in this transgenic mouse model, which might underlie the observed social and cognitive behavioral impairments.
conclusionsOur results indicate that overexpressing the secreted form of Nrg1 is sufficient to cause schizophrenia-like behaviors in a mouse model, meaning the effect is independent of the transmembrane and C-terminal domains of Nrg1. Hence, genetic gain-of-function mutations of Nrg1 are also risk factors for schizophrenia.
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