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Yannick Poitelon, M Laura Feltri
In the peripheral nervous system, axons dictate the differentiation state of Schwann cells. Most of this axonal influence on Schwann cells is due to juxtacrine interactions between axonal transmembrane molecules (e.g., the neuregulin growth factor) and receptors on the Schwann cell (e.g., the ErbB2/ErbB3 receptor). The fleeting nature of this interaction together with the lack of synchronicity in the development of the Schwann cell population limits our capability to study this phenomenon in vivo. Here we present a simple Boyden Chamber-based method to study this important cell-cell interaction event...
2018: Methods in Molecular Biology
Rhona Mirsky, Kristjan R Jessen
Schwann cell precursors are the first defined stage in the generation of Schwann cells from the neural crest and represent the glial cell of embryonic nerves. Highly pure cultures of these cells can be obtained by enzymatic dissociation of nerves dissected from the limbs of 14- or 12-day-old rat and mouse embryos, respectively. Since Schwann cell precursors, unlike Schwann cells, are acutely dependent on axonal signals for survival, they require addition of trophic factors, typically β-neuregulin-1, for maintenance in cell culture...
2018: Methods in Molecular Biology
Chengqiang Wu, Chun Gui, Lang Li, Yiheng Pang, Zhongli Tang, Jing Wei
Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h...
April 2018: Experimental and Therapeutic Medicine
Elise Allender, Harvinderjeet Deol, Sarah Schram, Kathleen J Maheras, Alexander Gow, Eleanor H Simpson, Fei Song
Neuregulin1 (NRG1) is a differentiation factor that regulates glial development, survival, synaptogenesis, axoglial interactions, and microglial activation. We previously reported that a targeted NRG1 antagonist (HBD-S-H4) given intrathecally, reduces inflammatory microglial activation in a spinal cord pain model and a neurodegenerative disease mouse model in vivo, suggesting that it may have effects in neuroninflammatory and neuronal disorders. We hypothesized that expression of HBD-S-H4 in the central nervous system (CNS) could reduce disease severity in experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS)...
March 10, 2018: Journal of Neuroimmunology
Hadis Shakeri, Andreas B Gevaert, Dorien M Schrijvers, Guido R Y De Meyer, Gilles W De Keulenaer, Pieter-Jan D F Guns, Katrien Lemmens, Vincent F Segers
Aims: Cardiovascular ageing is a key determinant of life expectancy. Cellular senescence, a state of irreversible cell cycle arrest, is an important contributor to ageing due to the accumulation of damaged cells. Targeting cellular senescence could prevent age-related cardiovascular diseases. In this study, we investigated the effects of neuregulin-1 (NRG-1), an epidermal growth factor with cardioprotective and anti-atherosclerotic effects, on cellular senescence. Methods & results: Senescence was induced in cultured rat aortic endothelial cells (ECs) and aortic smooth muscle cells (SMCs) by 2 hours exposure to 30 µM hydrogen peroxide (H2O2)...
March 8, 2018: Cardiovascular Research
Maria Elena de Bellard, Blanca Ortega, Sothy Sao, Lino Kim, Joshua Herman, Nora Zuhdi
BACKGROUND: Trunk neural crest cells migrate rapidly along characteristic pathways within the developing vertebrate embryo. Proper trunk neural crest cell migration is necessary for the morphogenesis of much of the peripheral nervous system, melanocytes, and the adrenal medulla. Numerous molecules help guide trunk neural crest cell migration throughout the early embryo. RESULTS: Here, we show that the trophic factor NRG1 is a chemoattractant through in vitro chemotaxis assays and in vivo silencing via a DN-erbB receptor...
March 8, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Peng Zhang, Henry Kuang, Yanlin He, Sharon O Idiga, Siming Li, Zhimin Chen, Zhao Yang, Xing Cai, Kezhong Zhang, Matthew J Potthoff, Yong Xu, Jiandie D Lin
Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling...
March 8, 2018: JCI Insight
Nathalie Donis, Cécile Oury, Marie Moonen, Patrizio Lancellotti
Available data indicate that survivors of breast cancer and Hodgkin lymphoma who received mediastinal radiotherapy are at increased risk of developing radiation-induced cardiovascular diseases (RICVD) one or two decades after treatment. Although the risk with modern radiation treatment is likely to be lower in these patient groups, cardiotoxicity is still observed in a subset of patients. In addition, radiation-associated cardiovascular complications can, in the future, extend to other groups of cancer patients who are treated for tumors that are localized near the heart...
March 1, 2018: Expert Opinion on Pharmacotherapy
Rose Chesworth, Leonora E Long, Cynthia Shannon Weickert, Tim Karl
The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 ( Nrg1 ). We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice ( Nrg1 TM HET), which is known to have increased sensitivity to cannabis exposure...
2018: Frontiers in Psychiatry
Arsalan Alizadeh, Kallivalappil T Santhosh, Hardeep Kataria, Abdelilah S Gounni, Soheila Karimi-Abdolrezaee
BACKGROUND: Spinal cord injury (SCI) triggers a robust neuroinflammatory response that governs secondary injury mechanisms with both degenerative and pro-regenerative effects. Identifying new immunomodulatory therapies to promote the supportive aspect of immune response is critically needed for the treatment of SCI. We previously demonstrated that SCI results in acute and permanent depletion of the neuronally derived Neuregulin-1 (Nrg-1) in the spinal cord. Increasing the dysregulated level of Nrg-1 through acute intrathecal Nrg-1 treatment enhanced endogenous cell replacement and promoted white matter preservation and functional recovery in rat SCI...
February 21, 2018: Journal of Neuroinflammation
Steven F Grieco, Todd C Holmes, Xiangmin Xu
Experience-dependent critical period plasticity has been extensively studied in the visual cortex. Monocular deprivation during the critical period affects ocular dominance, limits visual performance, and contributes to the pathological etiology of amblyopia. Neuregulin-1 (NRG1) signaling through its tyrosine kinase receptor ErbB4 is essential for the normal development of the nervous system, and has been linked to neuropsychiatric disorders such as schizophrenia. We discovered recently that NRG1/ErbB4 signaling in PV neurons is critical for the initiation of critical period visual cortical plasticity by controlling excitatory synaptic inputs onto PV neurons and thus PV-cell mediated cortical inhibition that occurs following visual deprivation...
February 21, 2018: Journal of Comparative Neurology
Ya-Nan Wang, Dwight Figueiredo, Xiang-Dong Sun, Zhao-Qi Dong, Wen-Bing Chen, Wan-Peng Cui, Fang Liu, Hong-Sheng Wang, Hai-Wen Li, Heath Robinson, Er-Kang Fei, Bing-Xing Pan, Bao-Ming Li, Wen-Cheng Xiong, Lin Mei
Neuregulin3 (NRG3) is a growth factor of the neuregulin (NRG) family and a risk gene of various severe mental illnesses including schizophrenia, bipolar disorders, and major depression. However, the physiological function of NRG3 remains poorly understood. Here we show that loss of Nrg3 in GFAP-Nrg3 f/f mice increased glutamatergic transmission, but had no effect on GABAergic transmission. These phenotypes were observed in Nex-Nrg3 f/f mice, where Nrg3 was specifically knocked out in pyramidal neurons, indicating that Nrg3 regulates glutamatergic transmission by a cell-autonomous mechanism...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
J Dai, L-J Xu, G-D Han, H-L Sun, G-T Zhu, H-T Jiang, G-Y Yu, X-M Tang
OBJECTIVE: Spinal cord injury (SCI) is a severe trauma to the central nervous system. Long non-coding RNAs have been reported to play essential roles in spinal cord injury. This study mainly explored the role of micro-125 in the regulation of spinal cord injury by regulating STAT3. MATERIALS AND METHODS: The stable mouse model of cervical spinal cord contusion was established by Infinite Horizon spinal cord striker, and the model mice' motor function was analyzed...
February 2018: European Review for Medical and Pharmacological Sciences
Won-Yong Jeong, Hye-Young Yoo, Chan-Wha Kim
Corneal epithelial cells (CECs) play an important role in the function of the cornea, and are maintained by corneal epithelial stem cells (CESCs). Recent studies have shown that neuronal growth factors affect the proliferation and migration of CESCs. Neuregulin-1 (NR-1) is a neuronal growth factor that is expressed in the early stages of brain development. The aim of this study was to determine whether NR-1 activates corneal wound healing. We observed that NR-1 activated both proliferation and migration of CECs...
February 20, 2018: Growth Factors
Maria A Missinato, Manush Saydmohammed, Daniel A Zuppo, Krithika S Rao, Graham W Opie, Bernhard Kühn, Michael Tsang
Zebrafish regenerate cardiac tissue through proliferation of pre-existing cardiomyocytes and neovascularization. Secreted growth factors such as FGFs, IGF, PDGFs, and Neuregulin (Nrg) play essential roles in stimulating cardiomyocyte proliferation. These factors activate the Ras/MAPK pathway, which is finely controlled by the feedback attenuator Dual Specificity Phosphatase 6 (Dusp6), an ERK phosphatase. Here we show that suppressing Dusp6 function enhanced cardiac regeneration. Inactivation of Dusp6 by small molecules or by gene inactivation increased cardiomyocyte proliferation, coronary angiogenesis, and reduced fibrosis after ventricular resection...
February 14, 2018: Development
Pauli M Turunen, Lauri M Louhivuori, Verna Louhivuori, Jyrki P Kukkonen, Karl E Åkerman
Cell-cell communication plays a central role in the guidance of migrating neuronal precursor cells during the development of the cerebral cortex. Endocannabinoids (eCBs) have previously been shown to be one of the central factors regulating neuronal migration. In this study the effects of eCBs on different parameters, expected to affect embryonic cortical neuronal motility have been analyzed in neurosphere derived neuroblasts using time-lapse microscopy. Increased endogenous production of the endocannabinoid 2-arachidonyl glycerol (2-AG) causes bursts of neuroblast motility...
February 10, 2018: Neuroscience
Nika Schwartz, Michal Pellach, Yair Glick, Reuven Gil, Gahl Levy, Dorit Avrahami, Efrat Barbiro-Michaely, Yaakov Nahmias, Doron Gerber
The hepatitis C virus (HCV) non-structural protein 3 (NS3) is essential for HCV maturation. The NS3/4A protease is a target for several HCV treatments and is a well-known target for HCV drug discovery. The protein is membrane associated and thus probably interacts with other membrane proteins. However, the vast majority of known NS3 host partners are soluble proteins rather than membrane proteins, most likely due to lack of appropriate platforms for their discovery. Utilization of an integrated microfluidics platform enables analysis of membrane proteins in their native form...
February 10, 2018: New Biotechnology
Xuelian He, Liguo Zhang, Luis F Queme, Xuezhao Liu, Andrew Lu, Ronald R Waclaw, Xinran Dong, Wenhao Zhou, Grahame Kidd, Sung-Ok Yoon, Andres Buonanno, Joshua B Rubin, Mei Xin, Klaus-Armin Nave, Bruce D Trapp, Michael P Jankowski, Q Richard Lu
Deficits in Schwann cell-mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice...
February 12, 2018: Nature Medicine
Dehua Liao, Yujin Guo, Daxiong Xiang, Ruili Dang, Pengfei Xu, Hualin Cai, Lizhi Cao, Pei Jiang
Objective: Long-term use of doxorubicin (Dox) can cause neurobiological side effects associated with depression, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in neural function, much is still unknown concerning the biological link between the NRG1/ErbB pathway and the Dox-induced neurotoxicity. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the hippocampus of rats following Dox treatment...
2018: Drug Design, Development and Therapy
Ada Ledonne, Dalila Mango, Emanuele Claudio Latagliata, Giulia Chiacchierini, Annalisa Nobili, Robert Nisticò, Marcello D'Amelio, Stefano Puglisi-Allegra, Nicola Biagio Mercuri
The neurotrophic factors neuregulins (NRGs) and their receptors, ErbB tyrosine kinases, regulate neurotransmission, synaptic plasticity and cognitive functions and their alterations have been associated to different neuropsychiatric disorders. Group 1 metabotropic glutamate receptors (mGluRI)-dependent mechanisms are also altered in animal models of neuropsychiatric diseases, especially mGluRI-induced glutamatergic long-term depression (mGluRI-LTD), a form of synaptic plasticity critically involved in learning and memory...
February 7, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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