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Neuregulin-1

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https://www.readbyqxmd.com/read/28826413/neuregulin-1-nrg1-polymorphisms-linked-with-psychosis-transition-are-associated-with-enlarged-lateral-ventricles-and-white-matter-disruption-in-schizophrenia
#1
C A Bousman, V Cropley, P Klauser, J L Hess, A Pereira, R Idrizi, J Bruggemann, M S Mostaid, R Lenroot, T W Weickert, S J Glatt, I P Everall, S Sundram, A Zalesky, C S Weickert, C Pantelis
BACKGROUND: Two single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia. METHODS: Structural (n = 370) and diffusion (n = 465) magnetic resonance imaging data were obtained from affected and unaffected individuals predominantly of European descent...
August 22, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28822966/inhibitory-actions-of-the-nrg-1-erbb4-pathway-in-macrophages-during-tissue-fibrosis-in-heart-skin-and-lung
#2
Zarha Vermeulen, Anne-Sophie Hervent, Lindsey Dugaucquier, Leni Vandekerckhove, Miche Rombouts, Matthias Beyens, Dorien M Schrijvers, Guido R Y De Meyer, Stuart Maudsley, Gilles W De Keulenaer, Vincent Fm Segers
The neuregulin-1 (NRG-1)/ErbB system is an endothelium-controlled paracrine system modulating cardiac performance and adaptation. Recent studies indicate that NRG-1 has anti-fibrotic effects in the left ventricle (LV), which were explained by direct actions on cardiac fibroblasts. However, the NRG-1/ErbB system also regulates the function of macrophages. In this study, we hypothesized that the anti-fibrotic effect of NRG-1 in the heart is at least partially mediated through inhibitory effects on macrophages...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28817803/developmental-dysfunction-of-vip-interneurons-impairs-cortical-circuits
#3
Renata Batista-Brito, Martin Vinck, Katie A Ferguson, Jeremy T Chang, David Laubender, Gyorgy Lur, James M Mossner, Victoria G Hernandez, Charu Ramakrishnan, Karl Deisseroth, Michael J Higley, Jessica A Cardin
GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation. Using a conditional ErbB4 deletion, we tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in the postnatal maturation of cortical circuits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of cortical temporal organization and state dependence...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28796387/ulinastatin-inhibited-sepsis-induced-spinal-inflammation-to-alleviate-peripheral-neuromuscular-dysfunction-in-an-experimental-rat-model-of-neuromyopathy
#4
Fei Xie, Su Min, Jingyuan Chen, Jun Yang, Xin Wang
Sepsis initiates a neuroinflammatory cascade that contributes to spinal cord inflammation and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of this cascade. In this study, we tested the hypothesis that ulinastatin (ULI) inhibits sepsis-induced spinal inflammation to alleviate peripheral neuromuscular dysfunction through the TLR4/MyD88/NF-κB signaling pathway. Muscular function, spinal cord water content, and cytokine levels of spinal cord were tested in TLR4-inhibited rats subjected to cecal ligation and puncture (CLP)...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28796037/functional-prediction-of-mir-3144-5p-in-human-cardiac-myocytes-based-on-transcriptome-sequencing-and-bioinformatics
#5
Lei Ruan, Yi Yang, Yi Huang, Ling Ding, Cuntai Zhang, Xiaofen Wu
BACKGROUND: RAN guanine nucleotide release factor (RANGRF) encoding protein MOG1 plays an important role in cardiac arrhythmia, so we intended to investigate the regulatory miRNA of RANGRF and explore its potential regulatory mechanism in arrhythmogenesis. METHODS: Based on bioinformatic analysis, miR-3144-5p was predicted to be a regulatory miRNA of RANGRF, which were then validated through a dual-luciferase reporter plasmid assay. Subsequently, the expression level of miR-3144-5p in human cardiac myocytes (HCMs) was detected, followed by cell transfection with miR-3144-5p mimics...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#6
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#7
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28722233/cooperative-interaction-of-hepatocyte-growth-factor-and-neuregulin-regulates-schwann-cell-migration-and-proliferation-through-grb2-associated-binder-2-in-peripheral-nerve-repair
#8
Yoon Kyoung Shin, So Young Jang, Seoug Hoon Yun, Yun Young Choi, Byeol-A Yoon, Young Rae Jo, So Young Park, Min Gyoung Pak, Joo In Park, Hwan Tae Park
The sequential reactive changes in Schwann cell phenotypes in transected peripheral nerves, including dedifferentiation, proliferation and migration, are essential for nerve repair. Even though the injury-induced migratory and proliferative behaviors of Schwann cells resemble epithelial and mesenchymal transition (EMT) in tumors, the molecular mechanisms underlying this phenotypic change of Schwann cells are still unclear. Here we show that the reactive Schwann cells exhibit migratory features dependent on the expression of a scaffolding oncoprotein Grb2-associated binder-2 (Gab2), which was transcriptionally induced by neuregulin 1-ErbB2 signaling following nerve injury...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28698179/a-novel-regulatory-mechanism-of-smooth-muscle-%C3%AE-actin-expression-by-nrg-1-circacta2-mir-548f-5p-axis
#9
Yan Sun, Zhan Yang, Bin Zheng, Xin-Hua Zhang, Man-Li Zhang, Xue-Shan Zhao, Hong-Ye Zhao, Toru Suzuki, Jin-Kun Wen
Rationale: Neuregulin-1 (NRG-1) includes an extracellular EGF-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor (TGF)-β1,its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB receptor. However, NRG-1-ICD function in VSMCs remains unknown. Objective: Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Methods and Results: Immunofluorescence staining, Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) showed that NRG-1 was expressed in rat, mouse and human VSMCs and was upregulated and cleaved in response to TGF-β1...
July 11, 2017: Circulation Research
https://www.readbyqxmd.com/read/28680299/the-scaffolding-protein-grb2-associated-binder-1-in-skeletal-muscles-and-terminal-schwann-cells-regulates-postnatal-neuromuscular-synapse-maturation
#10
So Young Park, So Young Jang, Yoon Kyoung Shin, Dong Keun Jung, Byeol A Yoon, Jong Kook Kim, Young Rae Jo, Hye Jeong Lee, Hwan Tae Park
The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice...
June 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28675393/erbb4-signaling-in-the-prelimbic-cortex-regulates-fear-expression
#11
Y-H Chen, Y-J Lan, S-R Zhang, W-P Li, Z-Y Luo, S Lin, J-P Zhuang, X-W Li, S-J Li, J-M Yang, T-M Gao
Many psychiatric diseases such as post-traumatic stress disorder (PTSD) are characterized by abnormal processing of emotional stimuli particularly fear. The medial prefrontal cortex (mPFC) is critically involved in fear expression. However, the molecular mechanisms underlying this process are largely unknown. Neuregulin-1 (NRG1) reportedly regulates pyramidal neuronal activity via ErbB4 receptors, which are abundant in parvalbumin (PV)-expressing interneurons in the PFC. In this study, we aimed to determine how NRG1/ErbB4 signaling in the mPFC modulates fear expression and found that tone-cued fear conditioning increased NRG1 expression in the mPFC...
July 4, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28675388/disrupted-hippocampal-neuregulin-1-erbb3-signaling-and-dentate-gyrus-granule-cell-alterations-in-suicide
#12
I Mahar, B Labonte, S Yogendran, E Isingrini, L Perret, M A Davoli, A Rachalski, B Giros, G Turecki, N Mechawar
Neuregulin-1 (NRG1) and ErbB receptors have been associated with psychopathology, and NRG1-ErbB3 signaling has been shown to increase hippocampal neurogenesis and induce antidepressant-like effects. In this study, we aimed to determine whether deficits in NRG1 or ErbBs might be present in the hippocampus of suicide completers. In well-characterized postmortem hippocampal samples from suicides and matched sudden-death controls, we assessed gene expression and methylation using qRT-PCR and EpiTYPER, respectively...
July 4, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28668379/design-and-optimization-of-plga-microparticles-for-controlled-and-local-delivery-of-neuregulin-1-in-traumatic-spinal-cord-injury
#13
Kallivalappil T Santhosh, Arsalan Alizadeh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in significant tissue damage that underlies functional impairments. Pharmacological interventions to confer neuroprotection and promote cell replacement are essential for SCI repair. We previously reported that Neuregulin-1 (Nrg-1) is acutely and permanently downregulated after SCI. Nrg-1 is a critical growth factor for differentiation of neural precursor cells (NPCs) into myelinating oligodendrocytes. We showed that intrathecal delivery of Nrg-1 enhances oligodendrocyte replacement following SCI...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28656214/her2-regulates-cancer-stem-like-cell-phenotype-in-alk-translocated-nsclc
#14
Tiia Honkanen, Emmi Wilenius, Peppi Koivunen, Jussi P Koivunen
We have previously shown that cancer stem-like cells (CSLCs) can mediate therapy resistance in ALK translocated lung cancers. HER2 has been linked to CSLCs in breast cancers and, therefore, we wanted to assess whether HER2 has a role in CSLCs in ALK translocated cancers. ALK translocated cell lines, H3122 and H2228, with variable sensitivity to ALK inhibition were used in the study. HER2 overexpression or knockdown was induced by retro- or lentiviral infections and cells were treated with pharmacological agents targeting HER2 and ALK signaling...
June 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28646138/uniting-the-neuro-developmental-and-immunological-hypotheses-neuregulin-1-receptor-erbb-and-toll-like-receptor-activation-in-first-episode-schizophrenia
#15
Szabolcs Kéri, Csilla Szabó, Oguz Kelemen
Current pathophysiological models of schizophrenia focus on neurodevelopmental and immunological mechanisms. We investigated a molecular pathway traditionally linked to the neurodevelopmental hypothesis (neuregulin 1 - ErbB), and pathogen-associated pattern recognition receptors associated with the immune hypothesis (Toll-like receptors, TLRs). We recruited 42 first-episode, drug-naïve patients with schizophrenia and 42 matched healthy control subjects. In monocytes TLR4/TLR5 and ErbB expressions were measured with flow-cytometry...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#16
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28623147/neuregulin-1-protects-mouse-cerebellum-against-oxidative-stress-and-neuroinflammation
#17
Junping Xu, Chengliang Hu, Shuangxi Chen, Huifan Shen, Qiong Jiang, Peizhi Huang, Weijiang Zhao
Cerebellum undergoes degenerative changes in neurodegenerative diseases. Two main factors including oxidative stress and neuroinflammation mediate neurodegeneration. Neuregulin-1 (Nrg1) has been implicated in many neurodegenerative diseases, while the underlying mechanisms are unknown. We hypothesized that Nrg1 prevents oxidative stress and neuroinflammation in neurodegeneration. We found a positive correlation between Nrg1 protein levels and ErbB4 and ErbB2 receptor phosphorylation in microarrays of normal human cerebellar tissue...
June 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#18
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
September 2017: Glia
https://www.readbyqxmd.com/read/28608461/epidermal-growth-factor-signals-attenuate-phenotypic-and-functional-development-of-neocortical-gaba-neurons
#19
Hisaaki Namba, Tadasato Nagano, Eiichi Jodo, Satoshi Eifuku, Masao Horie, Hirohide Takebayashi, Yuriko Iwakura, Hidekazu Sotoyama, Nobuyuki Takei, Hiroyuki Nawa
Phenotypic development of neocortical GABA neurons is highly plastic and promoted by various neurotrophic factors such as neuregulin-1. A subpopulation of GABA neurons expresses not only neuregulin receptor (ErbB4) but also epidermal growth factor (EGF) receptor (ErbB1) during development, but the neurobiological action of EGF on this cell population is less understood than that of neuregulin-1. Here we examined the effects of exogenous EGF on immature GABA neurons both in culture and in vivo and also explored physiological consequences in adults...
June 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28577921/parent-of-origin-effects-on-schizophrenia-relevant-behaviours-of-type-iii-neuregulin-1-mutant-mice
#20
Kani Shang, David A Talmage, Tim Karl
A robust, disease-relevant phenotype is paramount to the validity of genetic mouse models, which are an important tool in understanding complex diseases. Recent evidence from genome-wide association studies suggests the genetic contribution of parents to offspring is not equivalent. Despite this, few studies to date have examined the potential impact of parent genotype (i.e. origin of mutation) on the offspring of disease-relevant genetic mouse models. To elucidate the potential impact of the sex of the mutant parent on offspring phenotype, we characterized male and female offspring of an established schizophrenia mouse model, which had been generated using two different breeding schemes, in a range of disease-relevant behaviours...
May 31, 2017: Behavioural Brain Research
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