scholarly journals Neuregulin 1 Type I Overexpression Is Associated with Reduced NMDA Receptor–Mediated Synaptic Signaling in Hippocampal Interneurons Expressing PV or CCK

eNeuro ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. ENEURO.0418-17.2018 ◽  
Author(s):  
Dimitrios Kotzadimitriou ◽  
Wiebke Nissen ◽  
Melinda Paizs ◽  
Kathryn Newton ◽  
Paul J. Harrison ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Type I ◽  
Neuregulin 1 ◽  
Synaptic Signaling

scholarly journals The ketogenic diet increases Neuregulin 1 expression via elevating histone acetylation and its anti-seizure effect requires ErbB4 kinase activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Wang ◽  
Jie Huang ◽  
Shan Yao ◽  
Jia-Hui Wu ◽  
Hui-Bin Li ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Ketogenic Diet ◽  
Chromatin Immunoprecipitation ◽  
Kinase Activity ◽  
Control Diet ◽  
Synaptic Activity ◽  
Therapeutic Interventions ◽  
Type I ◽  
Neuregulin 1

Abstract Background The ketogenic diet (KD)has been considered an effective treatment for epilepsy, whereas its underlying mechanisms remain obscure. We have previously reported that the KD feeding increased Neuregulin 1 (NRG1) expression in the hippocampus; disruption of NRG1 signaling by genetically deleting its receptor-ErbB4 abolished KD’s effects on inhibitory synaptic activity and seizures. However, it is still unclear about the mechanisms underlying the effect of KD on NRG1 expression and whether the effects of KD require ErbB4 kinase activity. Methods The effects of the KD on NRG1 expression were assessed via western blotting and real-time PCR. Acetylation level at the Nrg1 promoter locus was examined using the chromatin immunoprecipitation technique. Kainic acid (KA)-induced acute seizure model was utilized to examine the effects of KD and histone deacetylase inhibitor-TSA on seizures. Synaptic activities in the hippocampus were recorded with the technique of electrophysiology. The obligatory role of ErbB4 kinase activity in KD’s effects on seizures and inhibitory synaptic activity was evaluated by using ErbB kinase antagonist and transgenic mouse-T796G. Results We report that KD specifically increases Type I NRG1 expression in the hippocampus. Using the chromatin immunoprecipitation technique, we observe increased acetylated-histone occupancy at the Nrg1 promoter locus of KD-fed mice. Treatment of TSA dramatically elevates NRG1 expression and diminishes the difference between the effects of the control diet (CD) and KD. These data indicate that KD increases NRG1 expression via up-regulating histone acetylation. Moreover, both pharmacological and genetic inhibitions of ErbB4 kinase activity significantly block the KD’s effects on inhibitory synaptic activity and seizure, suggesting an essential role of ErbB4 kinase activity. Conclusion These results strengthen our understanding of the role of NRG1/ErbB4 signaling in KD and shed light on novel therapeutic interventions for epilepsy.

Altered neuregulin 1–erbB4 signaling contributes to NMDA> receptor hypofunction in schizophrenia

2006 ◽  
Vol 12 (7) ◽  
pp. 824-828 ◽  
Author(s):  
Chang-Gyu Hahn ◽  
Hoau-Yan Wang ◽  
Dan-Sung Cho ◽  
Konrad Talbot ◽  
Raquel E Gur ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Neuregulin 1

scholarly journals Transgenic Overexpression of the Type I Isoform of Neuregulin 1 Affects Working Memory and Hippocampal Oscillations but not Long-term Potentiation

2011 ◽  
Vol 22 (7) ◽  
pp. 1520-1529 ◽  
Author(s):  
Inga H. Deakin ◽  
Wiebke Nissen ◽  
Amanda J. Law ◽  
Tracy Lane ◽  
Riam Kanso ◽  
...  
Keyword(s):  
Working Memory ◽  
Long Term Potentiation ◽  
Type I ◽  
Neuregulin 1 ◽  
Term Potentiation

scholarly journals Altered hippocampal gene expression and structure in transgenic mice overexpressing neuregulin 1 (Nrg1) type I

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Inga H. Deakin ◽  
Beata R. Godlewska ◽  
Mary A. Walker ◽  
Guo-Jen Huang ◽  
Markus H. Schwab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Type I ◽  
Neuregulin 1

scholarly journals Transmembrane domain Nrg1 mutant mice show altered susceptibility to the neurobehavioural actions of repeated THC exposure in adolescence

2013 ◽  
Vol 16 (1) ◽  
pp. 163-175 ◽  
Author(s):  
Leonora E. Long ◽  
Rose Chesworth ◽  
Xu-Feng Huang ◽  
Iain S. McGregor ◽  
Jonathon C. Arnold ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Binding ◽  
Transmembrane Domain ◽  
Insular Cortex ◽  
Mutant Mice ◽  
Treatment Withdrawal ◽  
Wild Type ◽  
Neurotransmitter Receptor ◽  
Neuregulin 1 ◽  
Nmda Receptor Binding

Abstract Heavy cannabis abuse increases the risk of developing schizophrenia. Adolescents appear particularly vulnerable to the development of psychosis-like symptoms after cannabis use. To test whether the schizophrenia candidate gene neuregulin 1 (NRG1) modulates the effects of cannabinoids in adolescence, we tested male adolescent heterozygous transmembrane domain Nrg1 mutant (Nrg1 TM HET) mice and wild type-like littermates (WT) for their neurobehavioural response to repeated Δ9-tetrahydrocannabinol (THC, 10 mg/kg i.p. for 21 d starting on post-natal day 31). During treatment and 48 h after treatment withdrawal, we assessed several behavioural parameters relevant to schizophrenia. After behavioural testing we measured autoradiographic CB1, 5-HT2A and NMDA receptor binding. The hyperlocomotor phenotype typical of Nrg1 mutants emerged after drug withdrawal and was more pronounced in vehicle than THC-treated Nrg1 TM HET mice. All mice were equally sensitive to THC-induced suppression of locomotion. However, mutant mice appeared protected against inhibiting effects of repeated THC on investigative social behaviours. Neither THC nor Nrg1 genotype altered prepulse inhibition. Repeated adolescent THC promoted differential effects on CB1 and 5-HT2A receptor binding in the substantia nigra and insular cortex respectively, decreasing binding in WT while increasing it in Nrg1 TM HET mice. THC also selectively affected 5-HT2A receptor binding in several other regions in WT mice, whereas NMDA receptor binding was only affected in mutant mice. Overall, Nrg1 mutation does not appear to increase the induction of psychotomimetic symptoms by repeated adolescent THC exposure but may attenuate some of its actions on social behaviour and schizophrenia-relevant neurotransmitter receptor profiles.

In silico analysis of neuregulin 1 evolution in vertebrates

2010 ◽  
Vol 30 (4) ◽  
pp. 267-275 ◽  
Author(s):  
Chih-Fong Chou ◽  
Miwako Ozaki
Keyword(s):  
In Silico ◽  
Phylogenetic Trees ◽  
Biological Activities ◽  
Cell Communication ◽  
In Silico Analysis ◽  
Start Codon ◽  
Type I ◽  
Neuregulin 1 ◽  
Nuclear Localization Signals

NRG1 (neuregulin 1) belongs to the NRG family of EGF (epidermal growth factor)-like signalling molecules involved in cell–cell communication during development and disease. It plays important roles in the developing tissues of the nerves, heart and mammary glands. Particularly in neurobiology, NRG1 signalling is associated with synaptic transmission, myelination of Schwann cells and the human disease of schizophrenia. Many different isoforms of NRG1 make the molecule highly sophisticated in biological activities and a great diversity of in vivo functions. The nervous system is a common trait in all bilateria (higher animals), but based on the BLAST information from the currently available databases it appears that NRG1 orthologues can only be identified in vertebrates. The gene was analysed in silico for type I–IV CDSs (coding sequences) from ten vertebrate genomes. The gene loci, structures of coding-intronic sequences, ClustalW program analyses, phylogenetic trees and conserved motifs in ecto- and cyto-plasmic domains were analysed and compared. Here, we conclude that non-mammalian vertebrates mainly carry type I (may have evolved a spacer different from mammalian isoforms), II and III NRG1s. The type IV NRG1 N-terminal CDSs can be identified from most of the mammalian genomes studied; however, the corresponding rodent sequences lack the start codon. The evolutionary conservation of a CDS59-CDS24-CDS103 domain, intracellular phosphorylation sites and bipartite nuclear localization signals is of physiological significance.

scholarly journals Gene Therapy Overexpressing Neuregulin 1 Type I in Combination With Neuregulin 1 Type III Promotes Functional Improvement in the SOD1G93A ALS Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Guillem Mòdol-Caballero ◽  
Mireia Herrando-Grabulosa ◽  
Sergi Verdés ◽  
Belén García-Lareu ◽  
Neus Hernández ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Skeletal Muscles ◽  
Viral Vectors ◽  
Neuromuscular Junctions ◽  
Functional Improvement ◽  
Type I ◽  
Neuregulin 1 ◽  
Beneficial Effects ◽  
The Central Nervous System

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the neuromuscular system for which currently there is no effective therapy. Motoneuron (MN) degeneration involves several complex mechanisms, including surrounding glial cells and skeletal muscle contributions. Neuregulin 1 (NRG1) is a trophic factor present particularly in MNs and neuromuscular junctions. Our previous studies revealed that gene therapy overexpressing the isoform I (NRG1-I) in skeletal muscles as well as overexpressing the isoform III (NRG1-III) directly in the central nervous system are both effective in preserving MNs in the spinal cord of ALS mice, opening novel therapeutic approaches. In this study, we combined administration of both viral vectors overexpressing NRG1-I in skeletal muscles and NRG1-III in spinal cord of the SOD1G93A mice in order to obtain a synergistic effect. The results showed that the combinatorial gene therapy increased preservation of MNs and of innervated neuromuscular junctions and reduced glial reactivity in the spinal cord of the treated SOD1G93A mice. Moreover, NRG1 isoforms overexpression improved motor function of hindlimb muscles and delayed the onset of clinical disease. However, this combinatory gene therapy did not produce a synergic effect compared with single therapies, suggesting an overlap between NRG1-I and NRG1-III activated pathways and their beneficial effects.

Sign in / Sign up

Export Citation Format

Share Document