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https://www.readbyqxmd.com/read/28628197/vesicular-acetylcholine-transporter-vacht-overexpression-induces-major-modifications-of-striatal-cholinergic-interneuron-morphology-and-function
#1
Helena Janickova, Vania F Prado, Marco A M Prado, Salah El Mestikawy, Véronique Bernard
Striatal cholinergic interneurons (CIN) are pivotal for the regulation of the striatal network. Acetylcholine (ACh) released by CIN is centrally involved in reward behavior as well as locomotor or cognitive functions. Recently, BAC transgenic mice expressing channelrhodopsin-2 (ChR2) protein under the control of the choline acetyltransferase (ChAT) promoter (ChAT-ChR2) and displaying almost 50 extra copies of the VAChT gene were used to dissect cholinergic circuit connectivity and function using optogenetic approaches...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28590490/synthesis-resolution-and-in-vitro-evaluation-of-three-vesicular-acetylcholine-transporter-ligands-and-evaluation-of-the-lead-fluorine-18-radioligand-in-a-nonhuman-primate
#2
Xuyi Yue, Hongjun Jin, Hui Liu, Zonghua Luo, Xiang Zhang, Kota Kaneshige, Hubert P Flores, Joel S Perlmutter, Stanley M Parsons, Zhude Tu
The vesicular acetylcholine transporter (VAChT) is a reliable biomarker for assessing cholinergic dysfunction associated with dementia. We recently reported three new potent and selective carbon-11 labeled VAChT radiotracers. Herein, we report the resolution with a Chiralcel OD column of three additional fluorine containing VAChT ligands in which a fluoroethoxy or fluoroethylamino moiety was substituted for the methoxy group. An in vitro competitive binding assay showed that (-)-7 had high potency for VAChT (Ki-VAChT = 0...
June 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28553858/adrenergic-and-cholinergic-innervation-of-the-atrioventricular-valves-in-chinchilla-chinchilla-laniger
#3
Jacek Kuchinka, Monika Chrzanowska, Tadeusz Kuder
The arrangement of autonomous fibres was studied in the cardiac atrioventricular valves of small chinchillas. The dissected valves were stained entirely using the modified histochemical acetylcholine esterase technique (AChE) and the SPG-De la Torre method. Double immunocytochemical staining was also used for the expression of vesicular acetylcholine transporter (VAChT) and dopamine β hydroxylase (DBH). The study showed the presence of both cholinergic and adrenergic fibres, forming a kind of network on all cusps of both valves...
May 29, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/28550012/the-genetic-architecture-of-ovariole-number-in-drosophila-melanogaster-genes-with-major-quantitative-and-pleiotropic-effects
#4
Amanda S Lobell, Rachel R Kaspari, Yazmin L Serrano Negron, Susan T Harbison
Ovariole number has a direct role in the number of eggs produced by an insect, suggesting that it is a key morphological fitness trait. Many studies have documented the variability of ovariole number and its relationship to other fitness and life-history traits in natural populations of Drosophila However, the genes contributing to this variability are largely unknown. Here we conducted a genome-wide association study of ovariole number in a natural population of flies. Using mutations and RNAi-mediated knockdown, we confirmed the effects of twenty-four candidate genes on ovariole number, including a novel gene, anneboleyn (formerly CG32000), that impacts both ovariole morphology and numbers of offspring produced...
May 26, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28469181/expression-and-distribution-of-the-transient-receptor-potential-cationic-channel-a1-trpa1-in-the-human-clitoris-comparison-to-male-penile-erectile-tissue
#5
S Ückert, K Albrecht, A Bannowsky, M Sohn, M A Kuczyk, P Hedlund
The transient receptor potential cationic channel ankyrin 1 (TRPA1) is a channel protein assumed to act in various human tissues as mechano- and pain sensor and play a role in neurotransmission. The expression of TRPA has already been investigated in the human prostate and urethra, however, only very few studies have addressed the expression and distribution in the male and female genital tract. The present study aimed to investigate by means of immunohistochemistry (double-labeling technique, laser fluorescence microscopy) in the human clitoris and penile erectile tissue the localization of TRPA1 in relation to nNOS, the vasoactive intestinal polypeptide (VIP) and vesicular acetylcholine transporter (VAChT)...
May 4, 2017: International Journal of Impotence Research
https://www.readbyqxmd.com/read/28461009/reduced-vesicular-acetylcholine-transporter-favors-antidepressant-behaviors-and-modulates-serotonin-and-dopamine-in-female-mouse-brain
#6
Marina Pádua-Reis, Nayara S Aquino, Vinícius E M Oliveira, Raphael E Szawka, Marco A M Prado, Vânia F Prado, Grace S Pereira
Depression is extremely harmful to modern society. Despite its complex spectrum of symptoms, previous studies have mostly focused on the monaminergic system in search of pharmacological targets. However, other neurotransmitter systems have also been linked to the pathophysiology of depression. In this study, we provide evidence for a role of the cholinergic system in depressive-like behavior of female mice. We evaluated mice knockdown for the vesicular acetylcholine transporter (VAChT KD mice), which have been previously shown to exhibit reduced cholinergic transmission...
April 28, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28421605/cholinergic-glutamatergic-co-transmission-in-striatal-cholinergic-interneurons-new-mechanisms-regulating-striatal-computation
#7
REVIEW
Ornela Kljakic, Helena Janickova, Vania F Prado, Marco A M Prado
It is well established that neurons secrete neuropeptides and ATP with classical neurotransmitters; however, certain neuronal populations are also capable of releasing two classical neurotransmitters by a process named co-transmission. Although there has been progress in our understanding of the molecular mechanism underlying co-transmission, the individual regulation of neurotransmitter secretion and the functional significance of this neuronal 'bilingualism' is still unknown. Striatal cholinergic interneurons (CINs) have been shown to secrete glutamate (Glu) in addition to acetylcholine (ACh) and are recognized for their role in the regulation of striatal circuits and behavior...
April 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28420875/down-regulation-of-cholinergic-signaling-in-the-habenula-induces-anhedonia-like-behavior
#8
Seungrie Han, Soo Hyun Yang, Jin Yong Kim, Seojung Mo, Esther Yang, Ki Myung Song, Byung-Joo Ham, Naguib Mechawar, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28397704/the-influence-of-tsa-and-vpa-on-the-in-vitro-differentiation-of-bone-marrow-mesenchymal-stem-cells-into-neuronal-lineage-cells-gene-expression-studies
#9
Anna Fila-Danilow, Paulina Borkowska, Monika Paul-Samojedny, Malgorzata Kowalczyk, Jan Kowalski
INTRODUCTION: Epigenetic mechanisms regulate the transcription of genes, which can affect the differentiation of MSCs. The aim of the current work is to determine how the histone deacetylase inhibitors TSA and VPA affect the expression of neuronal lineage genes in a culture of rat MSCs (rMSCs). MATERIALS AND METHODS: We analyzed the expression of early neuron marker gene (Tubb3), mature neuron markers genes (Vacht, Th, Htr2a) and the oligodendrocyte progenitor marker gene (GalC)...
March 27, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28347632/do-spiroindolines-have-the-potential-to-replace-vesamicol-as-lead-compound-for-the-development-of-radioligands-targeting-the-vesicular-acetylcholine-transporter
#10
Marcel Lindemann, Winnie Deuther-Conrad, Rares Moldovan, Kondapalli Venkata Gowri Chandra Sekhar, Peter Brust, Barbara Wenzel
The vesicular acetylcholine transporter (VAChT) is an important target for in vivo imaging of neurodegenerative processes using positron emission tomography (PET). So far the development of VAChT PET radioligands is based on the single known lead compound vesamicol. In this study we investigated a recently published spiroindoline based compound class (Sluder et al., 2012), which was suggested to have potential in the development of VAChT ligands. Therefore, we synthesized a small series of N,N-substituted spiro[indoline-3,4'-piperidine] derivatives and determined their in vitro binding affinities toward the VAChT...
March 18, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28337539/homer1-vesl-1-in-the-rat-esophagus-focus-on-myenteric-plexus-and-neuromuscular-junction
#11
J Zimmermann, W L Neuhuber, M Raab
Homer1, a scaffolding protein of the postsynaptic density (PSD), enriched at excitatory synapses is known to anchor and modulate group I metabotropic glutamate receptors (mGluRs) and different channel- and receptor-proteins. Homer proteins are expressed in neurons of different brain regions, but also in non-neuronal tissues like skeletal muscle. Occurrence and location of Homer1 and mGluR5 in myenteric plexus and neuromuscular junctions (NMJ) of rat esophagus have yet not been characterized. We located Homer1 and mGluR5 immunoreactivity (-iry) in rat esophagus and focused on myenteric neurons, intraganglionic laminar endings (IGLEs) and NMJs, using double- and triple-label immunohistochemistry and confocal laser scanning microscopy...
March 23, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28289379/dichotomous-distribution-of-putative-cholinergic-interneurons-in-mouse-accessory-olfactory-bulb
#12
Sarah Marking, Kurt Krosnowski, Tatsuya Ogura, Weihong Lin
Sensory information processing in the olfactory bulb (OB) relies on diverse populations of bulbar interneurons. In rodents, the accessory OB (AOB) is divided into two bulbar regions, the anterior (aAOB) and posterior (pAOB), which differ substantially in their circuitry connections and associated behaviors. We previously identified and characterized a large number of morphologically diverse cholinergic interneurons in the main OB (MOB) using transgenic mice to visualize the cell bodies of choline acetyltransferase (ChAT-expressing neurons and immunolabeling (Krosnowski et al...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28188850/immunolocalization-of-the-vesicular-acetylcholine-transporter-in-larval-and-adult-drosophila-neurons
#13
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...
March 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28188302/vesicular-acetylcholine-transporter-defect-underlies-devastating-congenital-myasthenia-syndrome
#14
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...
March 14, 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
#15
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
#16
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
#17
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
#18
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 vesicular acetylcholine transporter (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...
April 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28162892/fast-camp-modulation-of-neurotransmission-via-neuropeptide-signals-and-vesicle-loading
#19
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
#20
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)...
March 5, 2017: European Journal of Pharmacology
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