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Alpha 7 nicotine

Hans Matsson, Cilla Söderhäll, Elisabet Einarsdottir, Maxime Lamontagne, Sanna Gudmundsson, Helena Backman, Anne Lindberg, Eva Rönmark, Juha Kere, Don Sin, Dirkje S Postma, Yohan Bossé, Bo Lundbäck, Joakim Klar
BACKGROUND: Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors. We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD. METHODS: Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking...
November 11, 2016: BMC Pulmonary Medicine
Sonya Marshall-Gradisnik, Samantha Johnston, Anu Chacko, Thao Nguyen, Peter Smith, Donald Staines
OBJECTIVE: The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca(2+)) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients...
November 10, 2016: Journal of International Medical Research
Kaori Yamada-Nomoto, Osamu Yoshino, Ikumi Akiyama, Akemi Ushijima, Yosuke Ono, Tomoko Shima, Akitoshi Nakashima, Shusaku Hayashi, Makoto Kadowaki, Yutaka Osuga, Shigeru Saito
OBJECTIVE: We investigated α-7 nAchR expression in human peritoneal macrophages and examined whether activation of nAchR might be a new therapy for endometriosis. MATERIALS AND METHODS: Human peritoneal fluid mononuclear cells (PFMC) were stimulated with lipopolysaccharide (LPS) in the presence of α-7 nAChR agonists. In a murine endometriosis model, α-7 nAChR modulators were administered. RESULTS: Human PFMC expressed α-7 nAChR at the mRNA and protein levels...
December 2016: American Journal of Reproductive Immunology: AJRI
X M Chen, F Q Li, S Yan, X C Wu, C L Tang
OBJECTIVE: To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. METHODS: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Michelle L Pershing, David Phenis, Valentina Valentini, Ana Pocivavsek, Derick H Lindquist, Robert Schwarcz, John P Bruno
RATIONALE: Levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs) and antagonist at glutamatergic N-methyl-D-aspartate receptors (NMDARs), are elevated in the brain of patients with schizophrenia (SZ). In rats, dietary exposure to KYNA's immediate precursor kynurenine during the last week of gestation produces neurochemical and cognitive deficits in adulthood that resemble those seen in patients with SZ. OBJECTIVES: The present experiments examined whether prenatal kynurenine exposure results in age-dependent changes in the kynurenine pathway (KP), expression of selected receptors, and cognitive function...
October 2016: Psychopharmacology
Marcella Reale, Ada Maria Tata
The α7 nicotinic receptor consists of identical subunits and is one of the most abundant acetylcholine receptor in the mammalian central nervous system. However its expression is also found in the peripheral nervous system as well as in the immune system and various peripheral tissues. Its function is involved in the regulation of a range of activities such as classical excitatory neurotransmission in some brain regions, modulation of the release of several neurotransmitters, regulation of neurite outgrowth, and even neuronal survival/death...
July 29, 2016: Central Nervous System Agents in Medicinal Chemistry
Martina Di Giovangiulio, Goele Bosmans, Elisa Meroni, Nathalie Stakenborg, Morgane Florens, Giovanna Farro, Pedro J Gomez-Pinilla, Gianluca Matteoli, Guy Boeckxstaens
Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR(-/-) mice...
June 14, 2016: Molecular Medicine
Xi Ling, Hong Zhang, Xi-qin Yi, Jin-feng Wu
OBJECTIVE: To observe the relatively specific effect of electroacupuncture (EA) of "Xiajuxu" (ST 39, the lower hesea paint of the small intestine), etc. on the level of serum TNF-alpha, lnterleukin-1 P (IL-1 P) and high mobility group protein B 1 (HMGB 1) contents, and duodenum a7 nicotinic acetyicholine receptor (nAchR) expression in duodenal ulcer rats, so as to explore its mechanisms underlying improving duodenal ulcer. METHODS: Sixty SD rats were randomly divided into 6 groups: normal control, model, Xiajuxu (ST 39), Zusanli (ST 36), Shangjuxu (ST 37) and Yanglingquan (GB 34)...
April 2016: Zhen Ci Yan Jiu, Acupuncture Research
Mami Noda, A I Kobayashi
Alpha 7 subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in microglia and are involved in the suppression of neuroinflammation. Over the past decade, many reports show beneficial effects of nicotine, though little is known about the mechanism. Here we show that nicotine inhibits lipopolysaccharide (LPS)-induced proton (H(+)) currents and morphological change by using primary cultured microglia. The H(+) channel currents were measured by whole-cell patch clamp method under voltage-clamp condition...
June 2, 2016: Journal of Physiological Sciences: JPS
Adonis Sfera, Michael Cummings, Carolina Osorio
Dehydration is one of the ten most frequent diagnoses responsible for the hospital admission of elderly in the United States. It is associated with increased mortality, morbidity and an estimated cost of 1.14 billion per year (Xiao et al., 2004; Schlanger et al., 2010; Pretorius et al., 2013; Frangeskou et al., 2015). Older individuals are predisposed to dehydration encephalopathy as a result of decreased total body water (TBW) and diminished sensation of thirst. We hypothesize that thirst blunting in older individuals is the result of a defective microRNA-6842-3p failing to silence the expression of the vesicular GABA transporters (VGAT) and alpha 7 cholinergic nicotinic receptors in the subfornical organ (SFO) of the hypothalamus...
2016: Frontiers in Molecular Biosciences
Alessandro Gialluisi, Alessia Visconti, Erik G Willcutt, Shelley D Smith, Bruce F Pennington, Mario Falchi, John C DeFries, Richard K Olson, Clyde Francks, Simon E Fisher
BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes)...
2016: Journal of Neurodevelopmental Disorders
Justin R King, Nadine Kabbani
Nicotinic acetylcholine receptors (nAChRs) modulate the growth and structure of neurons throughout the nervous system. Ligand stimulation of the α7 nAChR has been shown to regulate the large heterotrimeric GTP-binding protein (G protein) signaling in various types of cells. Here, we demonstrate a role for α7 nAChR/G protein interaction in the activation of the small (monomeric) RhoA GTPase leading to cytoskeletal changes during neurite growth. Treatment of PC12 cells with the α7 nAChR agonist choline or PNU-282987 was associated with an increase in RhoA activity and an inhibition in neurite growth...
August 2016: Journal of Neurochemistry
Muzaffar Abbas, Shafiqur Rahman
Evidence indicates that microglial activation contributes to the pathophysiology and maintenance of neuroinflammatory pain involving central nervous system alpha-7 nicotinic acetylcholine receptors. The objective of the present study was to determine the effects of 3a,4,5,9b-Tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), an alpha-7 nicotinic acetylcholine receptor positive allosteric modulator (PAM), on tactile allodynia and thermal hyperalgesia following lipopolysaccharide (LPS)-induced microglial activation in hippocampus, a neuroinflammatory pain model in mice...
July 15, 2016: European Journal of Pharmacology
Christoph T Zimmer, William T Garrood, A Mirel Puinean, Manuela Eckel-Zimmer, Martin S Williamson, T G Emyr Davies, Chris Bass
Spinosad, a widely used and economically important insecticide, targets the nicotinic acetylcholine receptor (nAChRs) of the insect nervous system. Several studies have associated loss of function mutations in the insect nAChR α6 subunit with resistance to spinosad, and in the process identified this particular subunit as the specific target site. More recently a single non-synonymous point mutation, that does not result in loss of function, was identified in spinosad resistant strains of three insect species that results in an amino acid substitution (G275E) of the nAChR α6 subunit...
June 2016: Insect Biochemistry and Molecular Biology
Helen M Kamens, Robin P Corley, Phillip A Richmond, Todd M Darlington, Robin Dowell, Christian J Hopfer, Michael C Stallings, John K Hewitt, Sandra A Brown, Marissa A Ehringer
Common SNPs in nicotinic acetylcholine receptor genes (CHRN genes) have been associated with drug behaviors and personality traits, but the influence of rare genetic variants is not well characterized. The goal of this project was to identify novel rare variants in CHRN genes in the Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) samples and to determine if low frequency variants are associated with antisocial drug dependence. Two samples of 114 and 200 individuals were selected using a case/control design including the tails of the phenotypic distribution of antisocial drug dependence...
September 2016: Behavior Genetics
Maju Mathew Koola
The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia, identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. Galantamine is an acetylcholinesterase inhibitor and a positive allosteric modulator of the α7 nicotinic receptors. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist. There is evidence to suggest that the combination of galantamine and memantine may be effective in the treatment of cognitive impairments in schizophrenia...
June 2016: Schizophrenia Research. Cognition
Natalia Gass, Wolfgang Weber-Fahr, Alexander Sartorius, Robert Becker, Michael Didriksen, Tine Bryan Stensbøl, Jesper Frank Bastlund, Andreas Meyer-Lindenberg, Adam J Schwarz
The 15q13.3 microdeletion copy number variation is strongly associated with schizophrenia and epilepsy. The CHRNA7 gene, encoding nicotinic acetylcholine alpha 7 receptors (nAChA7Rs), is hypothesized to be one of the main genes in this deletion causing the neuropsychiatric phenotype. Here we used a recently developed 15q13.3 microdeletion mouse model to explore whether an established schizophrenia-associated connectivity phenotype is replicated in a murine model, and whether positive modulation of nAChA7 receptor might pharmacologically normalize the connectivity patterns...
July 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Steven K Sutton, Kate Janse Van Rensburg, Kade G Jentink, David J Drobes, David E Evans
RATIONALE: Considerable research suggests that nicotine enhances cognitive control-related processes (e.g., attention, memory) among nicotine-deprived smokers, both in terms of behavior and neural indices (e.g., ERP, slow-wave EEG). Nicotine may also increase cognitive control among nonsmokers, and this may vary as a function of trait cognitive control. It is important to examine the effects of nicotine on cognitive control-related processes among nonsmokers as these effects may provide a path for the initiation of smoking...
June 2016: Psychopharmacology
Peter K Joshi, Krista Fischer, Katharina E Schraut, Harry Campbell, Tõnu Esko, James F Wilson
Lifespan is a trait of enormous personal interest. Research into the biological basis of human lifespan, however, is hampered by the long time to death. Using a novel approach of regressing (272,081) parental lifespans beyond age 40 years on participant genotype in a new large data set (UK Biobank), we here show that common variants near the apolipoprotein E and nicotinic acetylcholine receptor subunit alpha 5 genes are associated with lifespan. The effects are strongly sex and age dependent, with APOE ɛ4 differentially influencing maternal lifespan (P=4...
March 31, 2016: Nature Communications
Yu Xue, Jingshu Tang, Xiaozhuo Ma, Qing Li, Bingxue Xie, Yuchen Hao, Hongwei Jin, Kewei Wang, Guisen Zhang, Liangren Zhang, Lihe Zhang
Human α7 nicotinic acetylcholine receptor (nAChR) is a promising therapeutic target for the treatment of schizophrenia accompanied with cognitive impairment. Herein, we report the synthesis and agonistic activities of a series of indolizine derivatives targeting to α7 nAChR. The results show that all synthesized compounds have affinity to α7 nAChR and some give strong agonistic activity, particularly most active agonists show higher potency than control EVP-6124. The docking and structure-activity relationship studies provide insights to develop more potent novel α7 nAChR agonists...
June 10, 2016: European Journal of Medicinal Chemistry
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