ArticleMolecular psychiatry2018
Neuregulin-2 ablation results in dopamine dysregulation and severe behavioral phenotypes relevant to psychiatric disorders.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- NCOA3 as a Key Regulator in Diabetic Cognitive Dysfunction.Molecular neurobiology · 2026Article
- Targeting MAD2B as a strategy for ischemic stroke therapy.Journal of advanced research · 2025Article
- Down-regulation of neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential.Iranian journal of basic medical sciences · 2025Article
- Alterations in Neuroligin-2 and BDNF proteins associated with anxiety-like behavior in salicylate-induced tinnitus rats.IBRO neuroscience reports · 2024Article
- Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder.International journal of molecular sciences · 2024Article
- Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer.BMC medicine · 2024Review
- The risk status, signatures of adaptation, and environmental suitability of village-based indigenous chickens from certain regions of Limpopo and KwaZulu-Natal provinces of South Africa.Frontiers in genetics · 2024Article
- Seasonal remodeling of the progenitor pool and its distribution in the ewe mediobasal hypothalamus.Cell and tissue research · 2023Article
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- Long-term effects of prophylactic MgSOJournal of neuroscience research · 2023Article
- ER-PM Junctions on GABAergic Interneurons Are Organized by Neuregulin 2/VAP Interactions and Regulated by NMDA Receptors.International journal of molecular sciences · 2023Article
- Article
- Relevance of interactions between dopamine and glutamate neurotransmission in schizophrenia.Molecular psychiatry · 2022Review
- Toxic and Phenotypic Effects of AAV_Cre Used to Transduce Mesencephalic Dopaminergic Neurons.International journal of molecular sciences · 2022Article
- Developmental, neurochemical, and behavioral analyses of ErbB4 Cyt-1 knockout mice.Journal of neurochemistry · 2022Article
- Characterization of cell-cell communication in autistic brains with single-cell transcriptomes.Journal of neurodevelopmental disorders · 2022Article
- Dopamine System, NMDA Receptor and EGF Family Expressions in Brain Structures of Bl6 and 129Sv Strains Displaying Different Behavioral Adaptation.Brain sciences · 2021Article
- Source and Impact of the EGF Family of Ligands on Intestinal Stem Cells.Frontiers in cell and developmental biology · 2021Review
- Neuregulins in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2021Article
- Neuregulins 1, 2, and 3 Promote Early Neurite Outgrowth in ErbB4-Expressing Cortical GABAergic Interneurons.Molecular neurobiology · 2020Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function. NRG2 KOs have higher extracellular dopamine levels in the dorsal striatum but lower levels in the mPFC; a pattern with similarities to dopamine dysbalance in schizophrenia. Like ErbB4 KO mice, NRG2 KOs performed abnormally in a battery of behavioral tasks relevant to psychiatric disorders. NRG2 KOs exhibit hyperactivity in a novelty-induced open field, deficits in prepulse inhibition, hypersensitivity to amphetamine, antisocial behaviors, reduced anxiety-like behavior in the elevated plus maze and deficits in the T-maze alteration reward test-a task dependent on hippocampal and mPFC function. Acute administration of clozapine rapidly increased extracellular dopamine levels in the mPFC and improved alternation T-maze performance. Similar to mice treated chronically with N-methyl-d-aspartate receptor (NMDAR) antagonists, we demonstrate that NMDAR synaptic currents in NRG2 KOs are augmented at hippocampal glutamatergic synapses and are more sensitive to ifenprodil, indicating an increased contribution of GluN2B-containing NMDARs. Our findings reveal a novel role for NRG2 in the modulation of behaviors with relevance to psychiatric disorders.
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