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https://www.readbyqxmd.com/read/28188850/immunolocalization-of-the-vesicular-acetylcholine-transporter-in-larval-and-adult-drosophila-neurons
#1
Sridhar Boppana, Natalie Kendall, Opeyemi Akinrinsola, Daniel White, Krushali Patel, Hakeem Lawal
Vesicular acetylcholine transporter (VAChT) function is essential for organismal survival, mediating the packaging of acetylcholine (ACh) for exocytotic release. However, its expression pattern in the Drosophila brain has not been fully elucidated. To investigate the localization of VAChT, we developed an antibody against the C terminal region of the protein and we show that this antibody recognizes a 65KDa protein corresponding to VAChT on an immunoblot in both Drosophila head homogenates and in Schneider 2 cells...
February 7, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28188302/vesicular-acetylcholine-transporter-defect-underlies-devastating-congenital-myasthenia-syndrome
#2
Adi Aran, Reeval Segel, Kota Kaneshige, Suleyman Gulsuner, Paul Renbaum, Scott Oliphant, Tomer Meirson, Ariella Weinberg-Shukron, Yair Hershkovitz, Sharon Zeligson, Ming K Lee, Abraham O Samson, Stanley M Parsons, Mary-Claire King, Ephrat Levy-Lahad, Tom Walsh
OBJECTIVE: To identify the genetic basis of a recessive congenital neurologic syndrome characterized by severe hypotonia, arthrogryposis, and respiratory failure. METHODS: Identification of the responsible gene by exome sequencing and assessment of the effect of the mutation on protein stability in transfected rat neuronal-like PC12(A123.7) cells. RESULTS: Two brothers from a nonconsanguineous Yemeni Jewish family manifested at birth with severe hypotonia and arthrogryposis...
February 10, 2017: Neurology
https://www.readbyqxmd.com/read/28185725/synthesis-and-in-vitro-evaluation-of-5-substituted-benzovesamicol-analogs-containing-n-substituted-amides-as-potential-positron-emission-tomography-tracers-for-the-vesicular-acetylcholine-transporter
#3
Sara Roslin, Maria De Rosa, Winnie Deuther-Conrad, Jonas Eriksson, Luke R Odell, Gunnar Antoni, Peter Brust, Mats Larhed
Herein, new ligands for the vesicular acetylcholine transporter (VAChT), based on a benzovesamicol scaffold, are presented. VAChT is acknowledged as a marker for cholinergic neurons and a positron emission tomography tracer for VAChT could serve as a tool for quantitative analysis of cholinergic neuronal density. With an easily accessible triflate precursor, aminocarbonylations were utilized to evaluate the chemical space around the C5 position on the tetrahydronaphthol ring. Synthesized ligands were evaluated for their affinity and selectivity for VAChT...
January 25, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28185314/beta-3-adrenergic-receptor-is-expressed-in-acetylcholine-containing-nerve-fibers-of-the-human-urinary-bladder-an-immunohistochemical-study
#4
Ana Coelho, Tiago Antunes-Lopes, James Gillespie, Francisco Cruz
AIMS: To identify in the human bladder the structures which express the Beta-3 adrenoceptor (β3AR). METHODS: Human bladders from cadaveric organ donors (equally balanced in sex and age) were collected. Bladders were immediately fixed in paraformaldehyde and further processed for cryostat sectioning. Single and double immunohistochemistry was performed using antibodies against β3AR C-terminal, β3AR N-terminal, a pan-neuronal marker (β3-Tubulin) and markers of cholinergic (Vesicular Acetylcholine Transporter), adrenergic (Tyrosine Hidroxylase), and peptidergic (Calcitonin Gene-Related Peptide) nerve fibers...
February 10, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28169381/direct-access-to-the-optically-active-vacht-inhibitor-vesamicol-and-its-analogues-via-the-asymmetric-aminolysis-of-meso-epoxides-with-secondary-aliphatic-amines
#5
Arun Sharma, Jyoti Agarwal, Rama Krishna Peddinti
First highly enantioselective synthesis of biologically important vesamicol, benzovesamicol, and their derivatives was achieved via the desymmetrization of meso-epoxides with secondary aliphatic amines (4-phenylpiperidine derivatives) using a chiral [salenCo(iii)-BF4] catalyst at room temperature. All products were obtained in good yield and with excellent optical induction.
February 7, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28167805/transgenic-line-for-the-identification-of-cholinergic-release-sites-in-drosophila-melanogaster
#6
Katarina Pankova, Alexander Borst
The identification of neurotransmitter type used by a neuron is important for the functional dissection of neuronal circuits. In the model organism Drosophila melanogaster, several methods for discerning the neurotransmitter systems are available. Here, we expanded the toolbox for the identification of cholinergic neurons by generating a new line FRT-STOP-FRT-VAChT::HA that is a conditional tagged knock-in of the VAChT gene in its endogenous locus. Importantly, in comparison to already available tools for the detection of cholinergic neurons, the FRT-STOP-FRT-VAChT::HA allele also allows for identification of the subcellular localization of the cholinergic presynaptic release sites in a cell-specific manner...
February 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28162892/fast-camp-modulation-of-neurotransmission-via-neuropeptide-signals-and-vesicle-loading
#7
Wagner Steuer Costa, Szi-Chieh Yu, Jana F Liewald, Alexander Gottschalk
Cyclic AMP (cAMP) signaling augments synaptic transmission, but because many targets of cAMP and protein kinase A (PKA) may be involved, mechanisms underlying this pathway remain unclear. To probe this mechanism, we used optogenetic stimulation of cAMP signaling by Beggiatoa-photoactivated adenylyl cyclase (bPAC) in Caenorhabditis elegans motor neurons. Behavioral, electron microscopy (EM), and electrophysiology analyses revealed cAMP effects on both the rate and on quantal size of transmitter release and led to the identification of a neuropeptidergic pathway affecting quantal size...
February 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28132912/involvement-of-arterial-baroreflex-and-nicotinic-acetylcholine-receptor-%C3%AE-7-subunit-pathway-in-the-protection-of-metformin-against-stroke-in-stroke-prone-spontaneously-hypertensive-rats
#8
Jin-Min Guo, Li Zhang, Xue-Cai Niu, He Shu, Lei Wang, Ding-Feng Su, Ying Zhang, Ai-Jun Liu, De-Qiu Zhu, Jian-Jiang Xu
Stroke is a leading cause of mortality and disability worldwide. There is growing evidence that metformin (Met) has potent neuroprotective effects; however, its mechanisms remain unclear. We examined the role of the arterial baroreflex and cholinergic-α7 nicotinic acetylcholine receptor (α7nAChR) anti-inflammory pathway in the beneficial effects of Met against stroke. Stroke-prone spontaneously hypertensive rats (SHRSP) were used to observe stroke development indicated by lifespan of SHRSP and the ischemic injury induced by permanent middle cerebral artery occlusion (MCAO)...
January 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28129990/chiral-resolution-of-serial-potent-and-selective-%C3%AF-1-ligands-and-biological-evaluation-of-18-f-tz3108-in-rodent-and-the-nonhuman-primate-brain
#9
Xuyi Yue, Hongjun Jin, Zonghua Luo, Hui Liu, Xiang Zhang, Ethan D McSpadden, Linlin Tian, Hubert P Flores, Joel S Perlmutter, Stanley M Parsons, Zhude Tu
Twelve optically pure enantiomers were obtained using either crystallization or chiral high performance liquid chromatography (HPLC) separation methodologies to resolve six racemic sigma-1 (σ1) receptor ligands. The in vitro binding affinities of each enantiomer for σ1, σ2 receptors and vesicular acetylcholine transporter (VAChT) were determined. Out of the 12 optically pure enantiomers, five displayed very high affinities for σ1 (Ki<2nM) and high selectivity for σ1 versus σ2 and VAChT (>100-fold)...
February 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27987021/impaired-contraction-and-decreased-detrusor-innervation-in-a-female-rat-model-of-pelvic-neuropraxia
#10
Johanna L Hannan, Shelby A Powers, Vinson M Wang, Fabio Castiglione, Petter Hedlund, Trinity J Bivalacqua
INTRODUCTION AND HYPOTHESIS: Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI. METHODS: Female Sprague-Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured...
December 16, 2016: International Urogynecology Journal
https://www.readbyqxmd.com/read/27941337/cxcl12-regulates-the-cholinergic-locus-and-cht1-through-akt-signaling-pathway
#11
Jing Yan, Wenhui Zhao, Meixia Guo, Xuefei Han, Zhiwei Feng
BACKGROUND: CXCL12 is pivotal for cholinergic neurons, and it induces the expressions of several genes that are essential for synthesis and storage of acetylcholine(ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. The present study explored the impact of pharmacological Akt inhibition upon cholinergic gene expression. METHODS: Western blotting was employed to determine the level of p-AKT, RT-PCR to check the mRNA levels of and CHT1(choline transporter1),VAChT and ChAT, ELISA to decipher the secretion of ACh and the activity of choline acetyltransferase...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27911305/nitrosylation-of-vesicular-transporters-in-brain-of-amyloid-precursor-protein-presenilin-1-double-transgenic-mice
#12
Ying Wang, Zhu Zhou, Hua Tan, Shenghua Zhu, Yiran Wang, Yingxia Sun, Xin-Min Li, Jun-Feng Wang
Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer's disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27909858/distribution-and-morphology-of-cholinergic-cells-in-the-branchial-epithelium-of-zebrafish-danio-rerio
#13
Peter C Zachar, Wen Pan, Michael G Jonz
Acetylcholine is an excitatory neurotransmitter important for oxygen sensing in mammals. A cholinergic mechanism in the fish gill has been implicated in the hyperventilatory response to acute hypoxia; however, the identity and distribution of acetylcholine-containing cells in the gills is poorly defined. We test the hypothesis that cholinergic cells are present in the gill filament epithelium in zebrafish (Danio rerio), a model vertebrate for which oxygen chemoreceptors are well characterized, and that these cells would receive nervous innervation...
December 2, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#14
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27889925/deletion-of-the-vesicular-acetylcholine-transporter-from-pedunculopontine-laterodorsal-tegmental-neurons-modifies-gait
#15
Helena Janickova, Kaie Rosborough, Mohammed Al-Onaizi, Ornela Kljakic, Monica S Guzman, Robert Gros, Marco A M Prado, Vania F Prado
Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease (PD), have been suggested to be related to dysfunctional cholinergic signaling in the brainstem. We investigated how long-term loss of cholinergic signaling from mesopontine nuclei influence motor behaviors. We selectively eliminated the vesicular acetylcholine transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency (VAChT(E)(n1-Cre-flox/flox) )...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27826198/high-expression-of-muscarinic-acetylcholine-receptor-3-predicts-poor-prognosis-in-patients-with-pancreatic-ductal-adenocarcinoma
#16
Lingfu Zhang, Dianrong Xiu, Jun Zhan, Xiaokun He, Limei Guo, Jilian Wang, Ming Tao, Wei Fu, Hongquan Zhang
AIMS: Recent studies showed that muscarinic acetylcholine receptor 3 (M3), as a muscarinic acetylcholine receptor family member that plays an important role in normal physiological function, is engaged in cancer progression. However, the role of M3 in pancreatic ductal adenocarcinoma (PDAC) is not known. The aim of this study is to investigate the expression and prognostic value of M3 in patients with PDAC. MATERIALS AND METHODS: The localization and expression of M3 in PDAC were examined by immunohistochemistry...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27796869/zinc-transporter-3-znt3-as-an-active-substance-in-the-enteric-nervous-system-of-the-porcine-esophagus
#17
Joanna Wojtkiewicz, Krystyna Makowska, Ewa Bejer-Olenska, Sławomir Gonkowski
Zinc transporter 3 (ZnT3), a member of the SLC 30 zinc transporter family, is involved in the transport of zinc ions from the cytoplasm into synaptic vesicles or intracellular organelles. The aim of the present study was to investigate for the first time the percentage of ZnT3-like immunoreactive (ZnT3-LI) neurons in the enteric nervous system (ENS) of the porcine esophagus and denotation of their neurochemical coding. Routine double- and triple-immunofluorescence labeling of cervical, thoracic, and abdominal fragments of esophagus for ZnT3 with protein gene product (PGP 9...
October 30, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27773630/distribution-and-sub-types-of-afferent-fibre-in-the-mouse-urinary-bladder
#18
M S Rahnama'i, B T Biallosterski, Ph E V Van Kerrebroeck, G A van Koeveringe, J I Gillespie, S G de Wachter
AIM: Increased afferent fibre activity contributes to pathological conditions such as the overactive bladder syndrome. Nerve fibres running near the urothelium are considered to be afferent as no efferent system has yet been described. The aim of this study was to identify sub-types of afferent nerve fibres in the mouse bladder wall based on morphological criteria and analyse regional differences. MATERIALS AND METHODS: 27 bladders of six month old C57BL/6 mice were removed and tissues were processed for immunohistochemistry...
January 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27753972/os-11-05-superior-cervical-ganglionectomy-scgx-reduces-sympathetic-innervation-of-vertebrobasilar-arteries-but-does-not-affect-cerebrovascular-remodelling-in-the-adult-spontaneously-hypertensive-rat-shr
#19
Dawid Walas, Eva Von Roloff, Julian Paton
OBJECTIVE: Our hypothesis is that hypoperfusion of the brainstem is due to elevated vertebrobasilar artery resistance, triggers hypertension. We asked: is there a functional relationship between the sympathetic innervation to the vertebrobasilar system and its remodelling in the SHR? DESIGN AND METHOD: SHRs (11-12 weeks old) received either sham surgery or bilateral SCGx. Animals recovered for 14 days, were then perfused-fixed with 4% PFA and the vertebrobasilar arteries examined using both immunohistofluorecent staining of sympathetic (anti-DβH) and parasympathetic (anti-VAChT) fibres, and by cross sectional examination of vertebral and basilar arteries...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27713817/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#20
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
2016: Skeletal Muscle
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