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https://www.readbyqxmd.com/read/28445721/nacho-mediates-nicotinic-acetylcholine-receptor-function-throughout-the-brain
#1
Jose A Matta, Shenyan Gu, Weston B Davini, Brian Lord, Edward R Siuda, Anthony W Harrington, David S Bredt
Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse aspects of brain function and mediate behavioral and addictive properties of nicotine. Neuronal nAChRs derive from combinations of α and β subunits, whose assembly is tightly regulated. NACHO was recently identified as a chaperone for α7-type nAChRs. Here, we find NACHO mediates assembly of all major classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for receptor surface expression...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#2
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28440223/structural-insights-into-the-molecular-mechanisms-of-myasthenia-gravis-and-their-therapeutic-implications
#3
Kaori Noridomi, Go Watanabe, Melissa N Hansen, Gye Won Han, Lin Chen
The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28428759/morphological-regeneration-and-functional-recovery-of-neuromuscular-junctions-after-tourniquet-induced-injuries-in-mouse-hindlimb
#4
Huiyin Tu, Dongze Zhang, Ryan M Corrick, Robert L Muelleman, Michael C Wadman, Yu-Long Li
Tourniquet application and its subsequent release cause serious injuries to the skeletal muscle, nerve, and neuromuscular junction (NMJ) due to mechanical compression and ischemia-reperfusion (IR). Monitoring structural and functional repair of the NMJ, nerve, and skeletal muscle after tourniquet-induced injuries is beneficial in exploring potential cellular and molecular mechanisms responsible for tourniquet-induced injuries, and for establishing effective therapeutic interventions. Here, we observed long-term morphological and functional changes of the NMJ in a murine model of tourniquet-induced hindlimb injuries...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28420041/-18-f-nifene-test-retest-reproducibility-in-first-in-human-imaging-of-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors
#5
Patrick J Lao, Tobey J Betthauser, Dana L Tudorascu, Todd E Barnhart, Ansel T Hillmer, Charles K Stone, Jogeshwar Mukherjee, Bradley T Christian
The aim of this study was to examine the suitability of [(18) F]nifene, a novel α4β2* nicotinic acetylcholine receptor (nAChR) radiotracer, for in vivo brain imaging in a first-in-human study. METHODS: Eight healthy subjects (4M,4F;21-69,44±21yrs) underwent a [(18) F]nifene PET scan (200±3.7MBq), and seven underwent a second scan within 58±31days. Regional estimates of DVR were measured using the multilinear reference tissue model (MRTM2) with the corpus callosum as reference region...
April 18, 2017: Synapse
https://www.readbyqxmd.com/read/28417590/calcitonin-gene-related-peptide-cgrp-a-novel-target-for-alzheimer-s-disease
#6
REVIEW
Yogendra Singh, Gaurav Gupta, Birendra Shrivastava, Rajiv Dahiya, Juhi Tiwari, Madhu Ashwathanarayana, Rakesh Kumar Sharma, Mohit Agrawal, Anurag Mishra, Kamal Dua
Alzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid-β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene-related peptide (CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor-stimulating peptide...
April 17, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28416445/%C3%AE-o-conotoxin-gexiva-disulfide-bond-isomers-exhibit-differential-sensitivity-for-various-nicotinic-acetylcholine-receptors-but-retain-potency-and-selectivity-for-the-human-%C3%AE-9%C3%AE-10-subtype
#7
Dongting Zhangsun, Xiaopeng Zhu, Quentin Kaas, Yong Wu, David J Craik, J Michael McIntosh, Sulan Luo
Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct neuropharmacological properties that are involved in a range of neuropathological conditions, including pain, addiction, epilepsy, autism, schizophrenia, Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types of cancer. The α9α10 nAChR is a potential target in chronic pain, wound healing, the pathophysiology of the auditory system, and breast and lung cancers. αO-conotoxin GeXIVA is a potent antagonist of rat α9α10 nAChRs, with the 'bead' disulfide bond isomer displaying the lowest IC50 of the three possible isomers...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28412449/targeted-drug-delivery-system-to-neural-cells-utilizes-the-nicotinic-acetylcholine-receptor
#8
Rachel Huey, Barry O'Hagan, Paul McCarron, Susan Hawthorne
Drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. In order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (BBB) must be overcome. This work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (RDP). Characterization studies revealed that RDP could be conjugated to drug-loaded PLGA nanoparticles of average diameter 257...
April 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28410331/the-role-of-erbin-in-gts-21-regulating-inflammtory-responses-in-mdp-stimulated-macrophages
#9
Xiao-Jing Wu, Xu-Ming Yang, Xue-Min Song, Yang Xu, Jian-Guo Li, Yan-Lin Wang, Zong-Ze Zhang, Lin-Li Le, Hui Liang, Yin Zhang
OBJECTIVE: To explore the role of Erbin protein and nucleotide-binding oligomerization domain 2/receptor-interacting serine/threonine protein kinases (NOD2/RICK) in GTS-21 activating cholinergic anti-inflammatory pathway. METHODS: Experiments were randomly divided into four groups: normal control (NC) group, muramyl dipeptide (MDP) group, 10 μg/mL MDP, GTS-21 (GTS) group, 10 μg/mL MDP plus 50 μg/mL GTS-21 (α7 nAChRs agonist), Erbin shRNA interference (sh-Erbin) group: sh-Erbin RNA plus 10 μg/mL MDP and 50 μg/mL GTS-21...
May 2017: Shock
https://www.readbyqxmd.com/read/28408300/%C3%AE-9-nachr-knockout-mice-exhibit-dysregulation-of-stress-responses-affect-and-reward-related-behaviour
#10
Sarasa A Mohammadi, Thomas J Burton, MacDonald J Christie
The α9α10-subtype of nicotinic acetylcholine receptor (nAChR) has recently garnered interest in biomedicine and is being pursued as an analgesic target. However, the receptor exhibits diverse tissue distribution, the function of which is known to varying degrees, and targeting this receptor for clinical treatments without a broad understanding of its function may have adverse consequences. The α9α10-nAChR is expressed in the adrenal and pituitary glands, suggesting a potential role in the stress response, but little is known about its function in this tissue...
April 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28401925/menthol-enhances-nicotine-reward-related-behavior-by-potentiating-nicotine-induced-changes-in-nachr-function-nachr-upregulation-and-da-neuron-excitability
#11
Brandon J Henderson, Teagan R Wall, Beverley M Henley, Charlene H Kim, Sheri McKinney, Henry A Lester
Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone...
April 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28400736/nicotine-effects-and-receptor-expression-on-human-spermatozoa-possible-neuroendocrine-mechanism
#12
Rosita A Condorelli, Sandro La Vignera, Filippo Giacone, Linda Iacoviello, Laura M Mongioì, Giovanni Li Volti, Ignazio Barbagallo, Roberto Avola, Aldo E Calogero
The aim of this experimental study was to investigate the mechanism by which nicotine (NIC) alters spermatozoa and to evaluate the expression of nicotinic receptors (nAChR) subunits in human spermatozoa. We analyzed 30 healthy normozoospermic men. Spermatozoa were incubated with NIC 100 ng/ml and the nAChR antagonist, hexamethonium (HEX) (0, 100, 1,000, 10,000 ng/ml) for 3 and 24 h. The following sperm parameters evaluated: (a) progressive motility; (b) mitochondrial membrane potential (MMP); (c) chromatin compactness; (d) externalization of phosphatidylserine (PS); (e) late apoptosis; (f) viability; (g) DNA fragmentation; (h) degree of lipid peroxidation (LP) by flow cytometry; (i) nAChR subunits expression by quantitative Real Time PCR and (j) protein expression evaluation by Western blot analysis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28400502/cholinergic-agonists-reduce-blood-pressure-in-a-mouse-model-of-systemic-lupus-erythematosus
#13
Amber S Fairley, Keisa W Mathis
Increased inflammation arising from an abnormal immune response can damage healthy tissue and lead to disease progression. An important example of this is the accumulation of inflammatory mediators in the kidney, which can subsequently lead to hypertension and renal injury. The origin of this inflammation may involve neuro-immune interactions. For example, the novel vagus nerve-to-spleen mechanism known as the "cholinergic anti-inflammatory pathway" controls inflammation upon stimulation. However, if this pathway is dysfunctional, inflammation becomes less regulated and chronic inflammatory diseases such as hypertension may develop...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28398760/nicotine-impairs-macrophage-control-of-mycobacterium-tuberculosis
#14
Xiyuan Bai, Jerry A Stitzel, An Bai, Cristian A Zambrano, Matthew Phillips, Philippa Marrack, Edward D Chan
Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB) but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we utilized a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR) - mecamylamine - as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR...
April 11, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28396143/lethal-effects-of-an-insecticidal-spider-venom-peptide-involve-positive-allosteric-modulation-of-insect-nicotinic-acetylcholine-receptors
#15
Monique J Windley, Irina Vetter, Richard J Lewis, Graham M Nicholson
κ-Hexatoxins (κ-HXTXs) are a family of excitotoxic insect-selective neurotoxins from Australian funnel-web spiders that are lethal to a wide range of insects, but display no toxicity towards vertebrates. The prototypic κ-HXTX-Hv1c selectively blocks native and expressed cockroach large-conductance calcium-activated potassium (BKCa or KCa1.1) channels, but not their mammalian orthologs. Despite this potent and selective action on insect KCa1.1 channels, we found that the classical KCa1.1 blockers paxilline, charybdotoxin and iberiotoxin, which all block insect KCa1...
April 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28391535/discriminative-stimulus-properties-of-s-nicotine-a-drug-for-all-seasons
#16
John A Rosecrans, Richard Young
S(-)-Nicotine is the major pharmacologically active substance in tobacco and can function as an effective discriminative stimulus in both experimental animals and humans. In this model, subjects must detect and communicate the nicotine drug state versus the non-drug state. This review describes the usefulness of the procedure to study nicotine, presents a general overview of the model, and provides some relevant methodological details for the establishment of this drug as a stimulus. Once established, the (-)-nicotine stimulus can be characterized for dose response and time course effects...
April 9, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28386326/activation-of-the-%C3%AE-7-nicotinic-receptor-promotes-lipopolysaccharide-induced-conversion-of-m1-microglia-to-m2
#17
Qichun Zhang, Ying Lu, Huimin Bian, Liwei Guo, Huaxu Zhu
The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR) plays an essential role in the cholinergic anti-inflammatory pathway that regulates macrophage/microglia function in inflammation. Similar to M1 and M2 macrophages, M1 and M2 microglia exhibit pro-inflammation and anti-inflammation properties, respectively. In the present study, we analyzed function-associated phenotypes to detect the transformation of microglia with activation of α7 nAChRs. We used lentivirus-mediated shRNA to knockdown the expression of α7 nAChR in BV-2 microglia incubated with lipopolysaccharides (LPS, 0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386148/expression-of-nicotinic-acetylcholine-receptor-%C3%AE-4-and-%C3%AE-2-subunits-on-direction-selective-retinal-ganglion-cells-in-the-rabbit
#18
Jun-Seok Lee, Hyun-Jin Kim, Chang-Hyun Ahn, Chang-Jin Jeon
The direction selectivity of the retina is a distinct mechanism that is critical function of eyes for survival. The direction-selective retinal ganglion cells (DS RGCs) strongly respond to a preferred direction, but rarely respond to opposite direction or null directional visual stimuli. The DS RGCs are sensitive to acetylcholine, which is secreted from starburst amacrine cells (SACs) to the DS RGCs. Here, we investigated the existence and distribution of the nicotinic acetylcholine receptor (nAChR) α4 and β2 subunits on the dendritic arbors of the DS RGCs in adult rabbit retina using immunocytochemistry...
February 28, 2017: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/28373127/rp5063-an-atypical-antipsychotic-drug-with-a-unique-pharmacologic-profile-improves-declarative-memory-and-psychosis-in-mouse-models-of-schizophrenia
#19
Lakshmi Rajagopal, Sunoh Kwon, Mei Huang, Eric Michael, Laxminarayan Bhat, Marc Cantillon, Herbert Y Meltzer
Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D2, D3, D4, serotonin (5-HT)1A, and 5-HT2A receptors (Rs), full agonism at α4β2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT2B, 5-HT6, and 5-HT7Rs. Most atypical APDs are 5-HT2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied...
March 31, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28372298/effect-of-nicotine-on-the-proliferation-and-chondrogenic-differentiation-of-the-human-wharton-s-jelly-mesenchymal-stem-cells
#20
Xu Yang, Yongjian Qi, Léonore Avercenc-Leger, Jean-Baptiste Vincourt, Sébastien Hupont, Céline Huselstein, Hui Wang, Liaobin Chen, Jacques Magdalou
BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by a progressive and irreversible degeneration of articular cartilage. Among the environmental risk factors of OA, tobacco consumption features prominently, although, there is a great controversy regarding the role of tobacco smoking in OA development. Among the numerous chemicals present in cigarette smoke, nicotine is one of the most physiologically active molecules. OBJECTIVE: The aim of the study was (i) to measure the impact of nicotine on the proliferation and chondrogenic differentiation of mesenchymal stem cells from the human Wharton's jelly (hWJ-MSCs) into chondrocytes, (ii) to investigate whether the α7 nicotinic acetylcholine receptors (nAChRs) was expressed in hWJ-MSCs and could play a role in the process...
2017: Bio-medical Materials and Engineering
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