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Neuregulin-1

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https://www.readbyqxmd.com/read/28350885/glutamate-dependent-ectodomain-shedding-of-neuregulin-1-type-ii-precursors-in-rat-forebrain-neurons
#1
Yuriko Iwakura, Ran Wang, Naoko Inamura, Kazuaki Araki, Shigeki Higashiyama, Nobuyuki Takei, Hiroyuki Nawa
The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28338897/specialized-information-processing-deficits-and-distinct-metabolomic-profiles-following-tm-domain-disruption-of-nrg1
#2
Colm M P O'Tuathaigh, Naina Mathur, Matthew J O'Callaghan, Lynsey MacIntyre, Richard Harvey, Donna Lai, John L Waddington, Benjamin S Pickard, David G Watson, Paula M Moran
Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain...
March 11, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#3
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
February 15, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28322798/neuregulin-1-type-iii-knockout-mice-exhibit-delayed-migration-of-schwann-cell-precursors
#4
Yuki Miyamoto, Tomohiro Torii, Akito Tanoue, Kazuko Kawahara, Miyuki Arai, Hideki Tsumura, Toru Ogata, Motoshi Nagao, Nobuo Terada, Masahiro Yamamoto, Shou Takashima, Junji Yamauchi
In an embryonic developmental stage of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations. After birth, they eventually wrap around individual axons to form myelin sheaths, which insulate axons to increase the nerve conduction velocity. Some growth factors and adhesion molecules are known to control these developmental stages from in the fish to in the mammal. Neuregulin-1 (NRG1), which is composed of many alternative splicing variants, is such a growth factor...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28322273/neuregulin-2-ablation-results-in-dopamine-dysregulation-and-severe-behavioral-phenotypes-relevant-to-psychiatric-disorders
#5
L Yan, A Shamir, M Skirzewski, E Leiva-Salcedo, O B Kwon, I Karavanova, D Paredes, O Malkesman, K R Bailey, D Vullhorst, J N Crawley, A Buonanno
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...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28303795/neuregulin-1-functionalization-of-organic-fibers-for-schwann-cell-guidance
#6
Ilaria Tonazzini, Maria Moffa, Dario Pisignano, Marco Cecchini
The repair of peripheral nerve lesions is a clinical problem where the functional recovery is often far from being satisfactory, although peripheral nerves generally retain good potential for regeneration. Here, we develop a novel scaffold approach based on bioactive fibers of poly(ε-caprolactone) where nanotopographical guidance and neuregulin 1 (NRG1) cues are combined. We interface them with rat primary Schwann cells (SCs), the peripheral glial cells that drive initial regeneration of injured nerves, and found that the combination of NRG1 with parallel nano-fibrous topographies is effective in improving SC growth up to 72 h, alignment to fiber topography, and bipolar differentiation, opening original perspectives for nerve repair applications...
April 18, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28278176/cuzd1-is-a-critical-mediator-of-the-jak-stat5-signaling-pathway-that-controls-mammary-gland-development-during-pregnancy
#7
Janelle Mapes, Quanxi Li, Athilakshmi Kannan, Lavanya Anandan, Mary Laws, John P Lydon, Indrani C Bagchi, Milan K Bagchi
In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1), expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28275713/axonal-type-iii-nrg1-controls-glutamate-synapse-formation-and-glua2-trafficking-in-hippocampal-accumbens-connections
#8
Chongbo Zhong, Wendy Akmentin, Chuang Du, Lorna W Role, David A Talmage
Altered neuregulin 1 (Nrg1)/ErbB signaling and glutamatergic hypofunction have been implicated in the pathophysiology of schizophrenia. Here, we employed gene chimeric ventral hippocampus (vHipp)-nucleus accumbens (nAcc) coculture from mouse, electrophysiology, immunocytochemistry, FM1-43 vesicle fusion, and electron microscopy techniques to examine the pre- and postsynaptic mechanisms of genetic deficits in Nrg1/ErbB signaling-induced glutamatergic dysfunctions. Reduced presynaptic type III Nrg1 expression along vHipp axons decreases the number of glutamate synapses and impairs GluA2 trafficking in the postsynaptic nAcc neurons, resulting in decreased frequency and amplitude of miniature EPSCs (mEPSCs)...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28273943/increased-nrg1-erbb4-signaling-in-human-symptomatic-epilepsy
#9
Jun-Ming Zhu, Ke-Xin Li, Shu-Xia Cao, Xiao-Juan Chen, Chen-Jie Shen, Ying Zhang, Hong-Yan Geng, Bi-Qing Chen, Hong Lian, Jian-Min Zhang, Xiao-Ming Li
Previous studies have shown that the neuregulin 1 (NRG1)-ErbB4 signaling pathway may regulate the excitability of fast-spiking neurons in the frontal cortex and participate in primary epilepsy pathogenesis. However, the exact roles and mechanism for NRG1/ErbB4 in human symptomatic epilepsy are still unclear. Using fresh human symptomatic epilepsy tissues, we found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex. In addition, NRG1-ErbB4 signaling suppressed phosphorylation of GluN2B at position 1472 by Src kinase, and decreased levels of phosphorylation level of GluN2B and Src were detected in human symptomatic epilepsy tissues...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271613/qiliqiangxin-protects-against-anoxic-injury-in-cardiac-microvascular-endothelial-cells-via-nrg-1-erbb-pi3k-akt-mtor-pathway
#10
Jingfeng Wang, Jingmin Zhou, Yanyan Wang, Chunjie Yang, Mingqiang Fu, Jingjing Zhang, Xueting Han, Zhiming Li, Kai Hu, Junbo Ge
Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary-like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase-3 activity...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28267150/ablation-of-neuropsin-neuregulin-1-signaling-imbalances-erbb4-inhibitory-networks-and-disrupts-hippocampal-gamma-oscillation
#11
M Kawata, S Morikawa, S Shiosaka, H Tamura
Parvalbumin-expressing interneurons are pivotal for the processing of information in healthy brain, whereas the coordination of these functions is seriously disrupted in diseased brain. How these interneurons in the hippocampus participate in pathological functions remains unclear. We previously reported that neuregulin 1 (NRG1)-ErbB4 signaling, which is actuated by neuropsin, is important for coordinating brain plasticity. Neuropsin cleaves mature NRG1 (bound to extracellular glycosaminoglycans) in response to long-term potentiation or depression, liberating a soluble ligand that activates its receptor, ErbB4...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28235789/erbb-signaling-attenuates-pro-inflammatory-activation-of-non-classical-monocytes
#12
Sergey Ryzhov, Anton Matafonov, Cristi L Galindo, Qinkun Zhang, Truc-Linh Tran, Daniel P Lenihan, Carrie Geisberg Lenneman, Igor Feoktistov, Douglas B Sawyer
Immune activation in chronic systolic heart failure (HF) correlates with disease severity and prognosis. Recombinant neuregulin-1 (NRG-1) is being developed as a possible therapy for HF based on activation of ERBB receptors in cardiac cells. Work in animal models of HF led us to hypothesize that there may be direct effects of NRG-1 on immune system activation and inflammation. We investigated the expression of ERBB receptors and the effect of the recombinant NRG-1 isoform glial growth factor 2 (GGF2) in subpopulations of peripheral blood mononuclear cells in subjects with HF...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28225915/exogenous-neuregulin-1-attenuates-stz-induced-diabetic-peripheral-neuropathic-pain-in-rats
#13
Fang Zhou, Zhongyuan Xia, Kang Liu, Qin Zhou
Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed...
January 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28208769/localisation-microscopy-of-breast-epithelial-erbb-2-receptors-and-gap-junctions-trafficking-after-%C3%AE-irradiation-neuregulin-1%C3%AE-and-trastuzumab-application
#14
Götz Pilarczyk, Ines Nesnidal, Manuel Gunkel, Margund Bach, Felix Bestvater, Michael Hausmann
In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin- 1 β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ -irradiation or alternatively neuregulin- 1 β application mobilized ErbB receptors in a nucleograde fashion-a process attenuated by trastuzumab antibody application...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28198409/electrical-stimulation-using-conductive-polymer-polypyrrole-counters-reduced-neurite-outgrowth-of-primary-prefrontal-cortical-neurons-from-nrg1-ko-and-disc1-li-mice
#15
Qingsheng Zhang, Dorna Esrafilzadeh, Jeremy M Crook, Robert Kapsa, Elise M Stewart, Eva Tomaskovic-Crook, Gordon G Wallace, Xu-Feng Huang
Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia. Electrical stimulation using conductive polymers has been shown to stimulate neurite outgrowth of differentiating human neural stem cells. This study investigated the use of the electroactive conductive polymer polypyrrole (Ppy) to counter impaired neurite outgrowth of primary pre-frontal cortical (PFC) neurons from NRG1-knock out (NRG1-KO) and DISC1-locus impairment (DISC1-LI) mice...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191772/human-induced-pluripotent-cell-derived-sensory-neurons-for-fate-commitment-of-bone-marrow-derived-schwann-cells-implications-for-remyelination-therapy
#16
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28190554/neuregulin-1-is-involved-in-enteric-nervous-system-development-in-zebrafish
#17
Jiarui Pu, Shaotao Tang, Qiangsong Tong, Guobin Wang, Haibo Jia, Qiong Jia, Kang Li, Dan Li, Dehua Yang, Jun Yang, Hang Li, Shuai Li, Hong Mei
BACKGROUND: Hirschsprung's disease (HD, also known as congenital colon aganglionosis) is a congenital disorder characterized by the absence of intramural ganglion cells in the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. Recent studies have indicated neuregulin 1 (NRG1) as a new candidate gene involved in the development of the enteric nervous system (ENS) in humans. METHODS: In our study, we investigated the role of NRG1 in zebrafish ENS development by assessing NRG1 expression patterns during ENS development...
January 23, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28174059/alterations-of-myelin-morphology-and-oligodendrocyte-development-in-early-stage-of-alzheimer-s-disease-mouse-model
#18
Yu Wu, Yuanlin Ma, Zhuo Liu, Qi Geng, Zexin Chen, Yan Zhang
Alzheimer's disease (AD) is the most common cause to dementia and predicted to influence about 35 million people by the end of 2050. In this study, we discover alterations of myelin morphology in hippocampus tissues of 2-month-old APP/PS1 mouse. Myelin sheath is thicker and internodal distance is shorter in APP/PS1 mouse. Oligodendrocytes, differentiated from oligodendrocytes progenitor cells (OPCs), are responsible for formation and maintenance of myelin sheath in central nervous system (CNS). Our current results demonstrate that the oligodendrocytes development is disordered in 2-month-old APP/PS1 mouse...
March 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28094814/meta-analysis-reveals-associations-between-genetic-variation-in-the-5-and-3-regions-of-neuregulin-1-and-schizophrenia
#19
M S Mostaid, S G Mancuso, C Liu, S Sundram, C Pantelis, I P Everall, C A Bousman
Genetic, post-mortem and neuroimaging studies repeatedly implicate neuregulin-1 (NRG1) as a critical component in the pathophysiology of schizophrenia. Although a number of risk haplotypes along with several genetic polymorphisms in the 5' and 3' regions of NRG1 have been linked with schizophrenia, results have been mixed. To reconcile these conflicting findings, we conducted a meta-analysis examining 22 polymorphisms and two haplotypes in NRG1 among 16 720 cases, 20 449 controls and 2157 family trios. We found significant associations for three polymorphisms (rs62510682, rs35753505 and 478B14-848) at the 5'-end and two (rs2954041 and rs10503929) near the 3'-end of NRG1...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28089851/neuregulin-1-mutant-mice-indicate-motor-and-sensory-deficits-indeed-few-references-for-schizophrenia-endophenotype-model
#20
Silvia Schneider, Katja Götz, Carmen Birchmeier, Herbert Schwegler, Thomas Roskoden
Neuregulins (Nrg) are a gene family that binds to tyrosine kinase receptors of the ErbB family. The protein of Nrg1 is to be involved in heart formation, migration of neurons, axonal pathfinding and synaptic function. A relation between Nrg1 and schizophrenia is assumed. Chronic impairment in schizophrenia is characterized by different positive and negative symptoms. Detectable markers of this disease in human and in animal models are activity, social behavior and sensory processing. In this study we compared heterozygous Nrg1 mutant mice in behavior and quantification of dopaminergic and serotoninergic neurons with wild type-like littermates...
January 13, 2017: Behavioural Brain Research
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