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https://www.readbyqxmd.com/read/29054611/maternal-undernutrition-during-lactation-alters-nicotine-reward-and-dopac-dopamine-ratio-in-cerebral-cortex-in-adolescent-mice-but-does-not-affect-nicotine-induced-nachrs-upregulation
#1
Ana C Dutra-Tavares, Juliana O Silva, André L Nunes-Freitas, Vinícius M S Guimarães, Ulisses C Araújo, Ellen P S Conceição, Egberto G Moura, Patrícia C Lisboa, Cláudio C Filgueiras, Alex C Manhães, Yael Abreu-Villaça, Anderson Ribeiro-Carvalho
Early undernutrition causes long lasting alterations that affect the response to psychoactive drugs. Particularly, undernutrition during lactation affects the acute locomotor response to nicotine during adolescence, but the reward effect of continued exposure to nicotine remains unknown. The goal of this study was to investigate the effects of undernutrition during lactation on the nicotine susceptibility indexed via conditioned place preference (CPP), on dopamine content and turnover and on nicotine-induced nicotinic cholinergic receptor (nAChR) upregulation in the cerebral cortex, midbrain and hippocampus of adolescent mice...
October 17, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29050783/design-and-synthesis-of-a-novel-series-of-1-s-2r-4-s-3h-4-azaspiro-benzo-4-5-imidazo-2-1-b-oxazole-2-2-bicyclo-2-2-2-octanes-with-high-affinity-for-the-%C3%AE-7-neuronal-nicotinic-receptor
#2
James Cook, F Christopher Zusi, Matthew D Hill, Haiquan Fang, Bradley Pearce, Hyunsoo Park, Lizbeth Gallagher, Ivar M McDonald, Linda Bristow, John E Macor, Richard E Olson
We describe an efficient and convergent synthesis of a series of (1'S,2R,4'S)-3H-4'-azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2'-bicyclo[2.2.2]octanes] displaying potency for the α7 nicotinic acetylcholine receptor (nAChR) and good selectivity vs. the related 5-HT3A receptor.
October 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29040265/analysis-of-peripheral-b-cells-and-autoantibodies-against-the-anti-nicotinic-acetylcholine-receptor-derived-from-patients-with-myasthenia-gravis-using-single-cell-manipulation-tools
#3
Tomohiro Makino, Ryuichi Nakamura, Maki Terakawa, Satoshi Muneoka, Kazuhiro Nagahira, Yuriko Nagane, Jyoji Yamate, Masakatsu Motomura, Kimiaki Utsugisawa
The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization...
2017: PloS One
https://www.readbyqxmd.com/read/29039603/blockade-of-%C3%AE-7-nicotinic-acetylcholine-receptors-inhibit-nicotine-induced-tumor-growth-and-vimentin-expression-in-non-small-cell-lung-cancer-through-mek-erk-signaling-way
#4
Chun Zhang, Ping Yu, Liang Zhu, Qingnan Zhao, Xiaotong Lu, Shuhong Bo
Nicotine can stimulate the progression of non-small cell lung cancer (NSCLC) through nicotinic acetylcholine receptors (nAChRs). The persistent proliferation of cancer cells is one of the key effects of nicotinic signaling. The present study aimed to clarify the mechanism of nicotine-induced proliferation in NSCLCs at the receptor subtype level. We have previously reported that there are various subtypes of nicotinic receptors expressed in NSCLC cell lines. In the present study, we demonstrated that blocking α7nAChRs agonized by nicotine could suppress the proliferation of H1299 cells in vitro and decrease H1299 tumor xenograft growth in nude mice...
October 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29036836/a-panel-of-slow-channel-congenital-myasthenic-syndrome-mice-reveals-a-unique-locomotor-behavioral-signature
#5
José G Grajales-Reyes, Aurian García-González, José C María-Ríos, Gary E Grajales-Reyes, Manuel Delgado-Vélez, Carlos A Báez-Pagán, Orestes Quesada, Christopher M Gómez, José A Lasalde-Dominicci
Muscle nicotinic acetylcholine receptor (nAChR) mutations can lead to altered channel kinetics and neuromuscular junction degeneration, a neurodegenerative disorder collectively known as slow-channel congenital myasthenic syndrome (SCCMS). A multivariate analysis using running wheels was used to generate activity profiles for a variety of SCCMS models, uncovering unique locomotor patterns for the different nAChR mutants. Particularly, the αL251T and ɛL269F mutations exhibit decreased event distance, duration, and velocity over a period of 24 hours...
October 13, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/29033834/tc299423-a-novel-agonist-for-nicotinic-acetylcholine-receptors
#6
Teagan R Wall, Brandon J Henderson, George Voren, Charles R Wageman, Purnima Deshpande, Bruce N Cohen, Sharon R Grady, Michael J Marks, Daniel Yohannes, Paul J Kenny, Merouane Bencherif, Henry A Lester
(E)-5-(Pyrimidin-5-yl)-1,2,3,4,7,8-hexahydroazocine (TC299423) is a novel agonist for nicotinic acetylcholine receptors (nAChRs). We examined its efficacy, affinity, and potency for α6β2(∗) (α6β2-containing), α4β2(∗), and α3β4(∗) nAChRs, using [(125)I]-epibatidine binding, whole-cell patch-clamp recordings, synaptosomal (86)Rb(+) efflux, [(3)H]-dopamine release, and [(3)H]-acetylcholine release. TC299423 displayed an EC50 of 30-60 nM for α6β2(∗) nAChRs in patch-clamp recordings and [(3)H]-dopamine release assays...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29033787/a-novel-ex-vivo-model-to-investigate-the-underlying-mechanisms-in-alzheimer-s-disease
#7
Emanuele Brai, Skye Stuart, Antoine-Scott Badin, Susan A Greenfield
Currently there is no widely accepted animal model reproducing the full pathological profile of Alzheimer's disease (AD), since the basic mechanisms of neurodegeneration are still poorly understood. We have proposed that the interaction between the α7 nicotinic acetylcholine receptor (α7-nAChR) and a recently discovered toxic peptide, cleaved from the acetylcholinesterase (AChE) C-terminus, could account for the aberrant processes occurring in AD. In this article we describe a new application on ex vivo model procedure, which combines the advantages of both in vivo and in vitro preparations, to study the effects of the AChE-derived peptide on the rat basal forebrain (BF)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29032010/dual-effects-of-insect-nachr-chaperone-ric-3-on-hybrid-receptor-promoting-assembly-on-endoplasmic-reticulum-but-suppressing-transport-to-plasma-membrane-on-xenopus-oocytes
#8
Haibo Bao, Xixia Xu, Wei Liu, Na Yu, Zewen Liu
Resistance to inhibitors of cholinesterase (RIC) -3 promotes the maturation (folding and assembly) of neuronal nicotinic acetylcholine receptors (nAChRs) as a molecular chaperone. The modulation effects of RIC-3 on homomeric α7 nAChRs are always positive, but its effects on heteromeric subtypes are inconsistent among reports. In this study, five RIC-3 isoforms were identified from Locusta migratoria. Four isoforms showed obvious effects on hybrid receptor Locα1/rβ2 expressed in Xenopus oocytes. As a representative, the co-expression of RIC-3v4 exhibited the decreased agonist responses (Imax) on oocytes, lower specific [(3)H]epibatidine binding (Bmax) on plasma membrane protein (PMP), and reduced subunit levels in PMP, which showed that the mature Locα1/rβ2 on the plasma membrane was decreased by the co-expression of RIC-3...
October 11, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29030971/nicotinic-acetylcholine-receptors-in-neuropathic-and-inflammatory-pain
#9
REVIEW
Arik J Hone, J Michael McIntosh
Nicotinic acetylcholine receptors (nAChRs) are actively being investigated as therapeutic targets for the treatment of pain and inflammation, but despite more than 30 years of research, there are currently no FDA approved analgesics that target these receptors. Much of the initial research effort focused on the α4β2 subtype, but more recently, additional subtypes have been identified as promising new therapeutic targets and include α6β4, α7 and α9-containing subtypes. This Review will focus on the distribution of these nAChRs in the cell types involved in neuropathic pain and inflammation as well as current pharmacological compounds that target them...
October 14, 2017: FEBS Letters
https://www.readbyqxmd.com/read/29030431/distinctive-modulation-of-dopamine-release-in-the-nucleus-accumbens-shell-mediated-by-dopamine-and-acetylcholine-receptors
#10
Jung Hoon Shin, Martin F Adrover, Veronica A Alvarez
Nucleus accumbens (NAc) shell shows unique dopamine (DA) signals in vivo and plays a unique role in DA dependent behaviors, such as reward-motivated learning and the response to drugs of abuse. A di-synaptic mechanism for DA release was reported and shown to require synchronized firing of cholinergic interneurons (CINs) and activation of nicotinic acetylcholine (ACh) receptors (nAChRs) in DA neuron (DAN) axons. The properties of this di-synaptic mechanism of DA transmission is not well understood in the NAc shell...
October 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29030271/noael-dose-of-a-neonicotinoid-pesticide-clothianidin-acutely-induce-anxiety-related-behavior-with-human-audible-vocalizations-in-male-mice-in-a-novel-environment
#11
Tetsushi Hirano, Shogo Yanai, Tadashi Takada, Naoki Yoneda, Takuya Omotehara, Naoto Kubota, Kiichi Minami, Anzu Yamamoto, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi
Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain...
October 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29024789/in-vitro-pharmacological-characterization-of-the-bispyridinium-non-oxime-compound-mb327-and-its-2-and-3-regioisomers
#12
K V Niessen, T Seeger, S Rappenglück, T Wein, G Höfner, K T Wanner, H Thiermann, F Worek
The primary toxic mechanism of organophosphorus compounds, i.e. nerve agents or pesticides, is based on the irreversible inhibition of acetylcholinesterase. In consequence of the impaired hydrolysis, the neurotransmitter acetylcholine accumulates in cholinergic synapses and disturbs functional activity of nicotinic and muscarinic acetylcholine receptors by overstimulation and subsequent desensitization. The resulting cholinergic syndrome will become acute life-threatening, if not treated adequately. The current standard treatment, consisting of administration of a competitive mAChR antagonist (e...
October 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29023569/pancreatic-and-snake-venom-presynaptically-active-phospholipases-a2-inhibit-nicotinic-acetylcholine-receptors
#13
Catherine A Vulfius, Igor E Kasheverov, Elena V Kryukova, Ekaterina N Spirova, Irina V Shelukhina, Vladislav G Starkov, Tatyana V Andreeva, Grazyna Faure, Marios Zouridakis, Victor I Tsetlin, Yuri N Utkin
Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein...
2017: PloS One
https://www.readbyqxmd.com/read/29018331/distinctive-roles-for-%C3%AE-7-and-%C3%AE-9-nicotinic-acetylcholine-receptors-in-inflammatory-and-autoimmune-responses-in-the-murine-experimental-autoimmune-encephalomyelitis-model-of-multiple-sclerosis
#14
Qiang Liu, Paul Whiteaker, Barbara J Morley, Fu-Dong Shi, Ronald J Lukas
Previous studies have demonstrated immunosuppressive and anti-inflammatory effects of nicotine, including in the experimental autoimmune encephalomyelitis (EAE) model in mice of some forms of multiple sclerosis (MS). Other studies using knock-out (KO) mice have implicated nicotinic acetylcholine (ACh) receptors containing α7, α9, or β2 subunits (α7*-, α9*- or β2*-nAChR) in different, disease-exacerbating or disease-ameliorating processes. These outcomes are in harmony with gene expression analyses showing nAChR subunit mRNA in many classes of immune system cell types...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29017931/acute-nicotine-disrupts-consolidation-of-contextual-fear-extinction-and-alters-long-term-memory-associated-hippocampal-kinase-activity
#15
Munir Gunes Kutlu, Brendan Garrett, Sana Gadiwalla, Jessica M Tumolo, Thomas J Gould
Previous research has shown that acute nicotine, an agonist of nAChRs, impaired fear extinction. However, the effects of acute nicotine on consolidation of contextual fear extinction memories and associated cell signaling cascades are unknown. Therefore, we examined the effects of acute nicotine injections before (pre-extinction) and after (post-extinction) contextual fear extinction on behavior and the phosphorylation of dorsal and ventral hippocampal ERK1/2 and JNK1 and protein levels on the 1st and 3rd day of extinction...
October 7, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29017814/pituitary-adenylate-cyclase-activating-polypeptide-induces-long-term-transcription-dependent-plasticity-and-remodeling-at-autonomic-synapses
#16
Eric R Starr, Joseph F Margiotta
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, widely expressed in the nervous system (Vaudry et al., 2009; Starr and Margiotta, 2016). At neuronal synapses where transmission is mediated by nicotinic acetylcholine receptor (nAChRs) transient PACAP exposure increases the frequency and amplitude (FS and AS) of spontaneous excitatory postsynaptic currents (sEPSCs) within minutes. This short-term (ST) plasticity requires high-affinity PACAP receptor (PAC1R) signaling via adenylate cyclase (AC), cyclic AMP (cAMP), Protein kinase A (PKA) and obligatory nAChR-dependent stimulation of nitric oxide (NO) synthesis to retrogradely increase presynaptic ACh release (Pugh et al...
October 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28993249/spider-acetylcholine-binding-proteins-an-alternative-model-to-study-the-interaction-between-insect-nachrs-and-neonicotinoids
#17
Haibo Bao, Xiangkun Meng, Zewen Liu
Acetylcholine binding proteins (AChBPs) are homologs of extracellular domains of nicotinic acetylcholine receptors (nAChRs) and serve as models for studies on nAChRs. Particularly, studies on invertebrate nAChRs that are limited due to difficulties in their heterologous expression have benefitted from the discovery of AChBPs. Thus far, AChBPs have been characterized only in aquatic mollusks, which have shown low sensitivity to neonicotinoids, the insecticides targeting insect nAChRs. However, AChBPs were also found in spiders based on the sequence and tissue expression analysis...
October 6, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28993233/the-distribution-of-the-alpha7-nicotinic-acetylcholine-receptor-in-healthy-aging-an-in-vivo-positron-emission-tomography-study-with-18-f-asem
#18
Jennifer M Coughlin, Yong Du, Hailey B Rosenthal, Stephanie Slania, Soo Min Koo, Andrew Park, Ghedem Solomon, Melin Vranesic, Inga Antonsdottir, Caroline L Speck, Kelly Rootes-Murdy, Alexandria Lerner, Steven P Rowe, Yuchuan Wang, Wojciech G Lesniak, Il Minn, Arnold Bakker, Gwenn S Smith, Robert F Dannals, Hiroto Kuwabara, Andrew Horti, Dean F Wong, Martin G Pomper
Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue. METHODS: The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21-86 years; median 57 years, interquartile range 52 years) using [(18)F]ASEM with positron emission tomography (PET) imaging...
October 7, 2017: NeuroImage
https://www.readbyqxmd.com/read/28991400/resistance-to-cycloxaprid-in-laodelphax-striatellus-is-associated-with-altered-expression-of-nicotinic-acetylcholine-receptor-subunits
#19
Yueliang Zhang, Yangchun Han, Qiong Yang, Lihua Wang, Peng He, Zewen Liu, Huifang Guo, Jichao Fang
BACKGROUND: Cycloxaprid is a new oxabridged cis-configuration neonicotinoid insecticide, the resistance development potential and underlying resistance mechanism of which were investigated in the small brown planthopper, Laodelphax striatellus (Fallén), an important agricultural pest of rice. RESULTS: A cycloxaprid-resistant strain (YN-CPD) only achieved 10-fold resistance, in contrast to 106-fold resistance to buprofezin and 332-fold resistance to chlorpyrifos achieved after exposure to similar selection pressure, and the cycloxaprid selected line showed no cross-resistance to the buprofezin and chlorpyrifos-selected resistance strains...
October 9, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28986583/effects-of-%C3%AE-conotoxin-imi-on-tnf-%C3%AE-il-8-and-tgf-%C3%AE-expression-by-human-macrophage-like-cells-derived-from-thp-1-pre-monocytic-leukemic-cells
#20
Alberto Padilla, Patricia Keating, James X Hartmann, Frank Marí
α7 nicotinic acetylcholine receptors (nAChRs) are ubiquitous in the nervous system and ensure important neurophysiological functionality for many processes. However, they are also found in cells of the immune system, where their role has been less studied. Here we report the pro-inflammatory effect of ImI, a well characterized conotoxin that inhibits α7 nAChRs, on differentiated THP-1 pre-monocyte macrophages (MDM) obtained by phorbol 12-myristate 13 acetate (PMA) treatment. Enzyme-linked immunosorbent assay (ELISA) performed on supernatant fluids of LPS challenged MDM showed ImI-mediated upregulation of pro-inflammatory cytokine TNF-α in an ImI concentration-dependent manner from 0...
October 6, 2017: Scientific Reports
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