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https://www.readbyqxmd.com/read/28225161/treatment-of-experimental-status-epilepticus-with-synergistic-drug-combinations
#1
Jerome Niquet, Roger Baldwin, Lucie Suchomelova, Lucille Lumley, Roland Eavey, Claude G Wasterlain
During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAA Rs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAA Rs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAA Rs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE...
February 22, 2017: Epilepsia
https://www.readbyqxmd.com/read/28213446/acetylcholine-release-in-prefrontal-cortex-promotes-gamma-oscillations-and-theta-gamma-coupling-during-cue-detection
#2
W M Howe, H J Gritton, N Lusk, Erik A Roberts, Vaughn L Hetrick, Joshua D Berke, Martin Sarter
The capacity for using external cues to guide behavior ("cue detection") constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined sub-second measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28210219/mice-lacking-m1-and-m3-muscarinic-acetylcholine-receptors-have-impaired-odor-discrimination-and-learning
#3
Wilson Chan, Sanmeet Singh, Taj Keshav, Ramita Dewan, Christian Eberly, Robert Maurer, Alexia Nunez-Parra, Ricardo C Araneda
The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1(-/-) and the M1/M3(-/-) knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/28209997/antisense-mir-132-blockade-via-the-ache-r-splice-variant-mitigates-cortical-inflammation
#4
Nibha Mishra, Lyndon Friedson, Geula Hanin, Uriya Bekenstein, Meshi Volovich, Estelle R Bennett, David S Greenberg, Hermona Soreq
MicroRNA (miR)-132 brain-to-body messages suppress inflammation by targeting acetylcholinesterase (AChE), but the target specificity of 3'-AChE splice variants and the signaling pathways involved remain unknown. Using surface plasmon resonance (SPR), we identified preferential miR-132 targeting of soluble AChE-R over synaptic-bound AChE-S, potentiating miR-132-mediated brain and body cholinergic suppression of pro-inflammatory cytokines. Inversely, bacterial lipopolysaccharide (LPS) reduced multiple miR-132 targets, suppressed AChE-S more than AChE-R and elevated inflammatory hallmarks...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209438/excessive-daytime-sleepiness-in-a-patient-with-coexisting-myotonic-dystrophy-type-1-myasthenia-gravis-and-graves-disease
#5
Katarzyna Kapica-Topczewska, Robert Pogorzelski, Joanna Tarasiuk, Wiesław Drozdowski, Piotr Lewczuk, Alina Kułakowska
A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles...
February 3, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/28209287/molecular-imaging-of-the-nicotinic-cholinergic-receptor-in-alzheimer-disease
#6
EDITORIAL
Gwenn S Smith
No abstract text is available yet for this article.
January 5, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28203147/astrocyte-dependent-slow-inward-currents-sics-participate-in-neuromodulatory-mechanisms-in-the-pedunculopontine-nucleus-ppn
#7
Adrienn Kovács, Balázs Pál
Slow inward currents (SICs) are known as excitatory events of neurons caused by astrocytic glutamate release and consequential activation of neuronal extrasynaptic NMDA receptors. In the present article we investigate the role of these astrocyte-dependent excitatory events on a cholinergic nucleus of the reticular activating system (RAS), the pedunculopontine nucleus (PPN). It is well known about this and other elements of the RAS, that they do not only give rise to neuromodulatory innervation of several areas, but also targets neuromodulatory actions from other members of the RAS or factors providing the homeostatic drive for sleep...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28197102/right-cervical-vagotomy-aggravates-viral-myocarditis-in-mice-via-the-cholinergic-anti-inflammatory-pathway
#8
Ge Li-Sha, Chen Xing-Xing, Wu Lian-Pin, Zhou De-Pu, Li Xiao-Wei, Lin Jia-Feng, Li Yue-Chun
The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a 'cholinergic anti-inflammatory pathway' dependent on the α7-nicotinic acetylcholine receptor (α7nAChR). Although the role of β-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28196601/cholinergic-signals-from-the-cns-regulate-g-csf-mediated-hsc-mobilization-from-bone-marrow-via-a-glucocorticoid-signaling-relay
#9
Halley Pierce, Dachuan Zhang, Claire Magnon, Daniel Lucas, John R Christin, Matthew Huggins, Gary J Schwartz, Paul S Frenette
Hematopoietic stem cells (HSCs) are mobilized from niches in the bone marrow (BM) to the blood circulation by the cytokine granulocyte colony-stimulating factor (G-CSF) through complex mechanisms. Among these, signals from the sympathetic nervous system regulate HSC egress via its niche, but how the brain communicates with the BM remains largely unknown. Here we show that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes G-CSF-elicited HSC mobilization via hormonal priming of the hypothalamic-pituitary-adrenal (HPA) axis...
February 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28196430/first-in-human-trial-of-a-type-i-positive-allosteric-modulator-of-alpha7-nicotinic-acetylcholine-receptors-pharmacokinetics-safety-and-evidence-for-neurocognitive-effect-of-avl-3288
#10
Kelvin W Gee, Ann Olincy, Richard Kanner, Lynn Johnson, Derk Hogenkamp, Josette Harris, Minhtam Tran, Stephen A Edmonds, William Sauer, Ryan Yoshimura, Timothy Johnstone, Robert Freedman
Type I positive allosteric modulators (PAMs) of the alpha7-nicotinic receptor enhance its cholinergic activation while preserving the spatiotemporal features of synaptic transmission and the receptor's characteristic rapid desensitization kinetics. Alpha7-nicotinic receptor agonists have shown promise for improving cognition in schizophrenia, but longer-term trials have been disappointing. Therefore, the type I PAM AVL-3288 was evaluated for safety and preliminary evidence of neurocognitive effect in healthy human subjects...
February 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28194438/a-role-for-muscarinic-receptors-in-neutrophil-extracellular-trap-formation-and-levamisole-induced-autoimmunity
#11
Carmelo Carmona-Rivera, Monica M Purmalek, Erica Moore, Meryl Waldman, Peter J Walter, H Martin Garraffo, Karran A Phillips, Kenzie L Preston, Jonathan Graf, Mariana J Kaplan, Peter C Grayson
Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study's objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28190393/significance-of-cholinergic-and-peptidergic-nerves-in-stress-induced-ulcer-and-malt-lymphoma-formation
#12
Masahiko Nakamura, Anders Øverby, Akina Uehara, Masaya Oda, Shinichi Takahashi, Somay Y Murayama, Hidenori Matsui
: Backgound: The role of enteric nerves has previously been demonstrated in the formation of several gastric diseases. In the present review, the significance of the cholinergic nerves in stress-induced ulcer formation as well as the importance of substance P in the formation of gastric MALT lymphoma is discussed. METHODS: The stress-induced ulcer was induced by the plaster bandage methods in rats. The gastric MALT lymphoma was formed by the peroral infection of gastric mucosal homogenate of the infected mouse in C57BL/6 mice...
February 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28188358/protective-effect-of-valproic-acid-in-streptozotocin-induced-sporadic-alzheimer-s-disease-mouse-model-possible-involvement-of-the-cholinergic-system
#13
Mirna Ezzat Sorial, Nesrine Salah El Dine El Sayed
Sporadic Alzheimer's disease (SAD) is a slowly progressive neurological disorder that is the most common form of dementia. Cholinergic system dysfunction and amyloid beta formation are the two main underlying pathological mechanisms for the disease development. In recent studies, insulin receptor desensitization and disturbances in the downstream effects of insulin receptor signaling were observed in the brains of Alzheimer's patients. Currently, intracereberoventricular (ICV) injection of streptozotocin (STZ) is found to induce behavioral, neurochemical, and structural alterations in animals resembling those found in SAD patients...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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
#14
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
#15
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/28185116/potential-acetylcholinesterase-inhibitors-molecular-docking-molecular-dynamics-and-in-silico-prediction
#16
Alessandra S Kiametis, Mônica A Silva, Luiz A S Romeiro, João B L Martins, Ricardo Gargano
This paper deals with molecular modeling of new therapeutic agents for treating the Alzheimer's disease. The therapeutic line adopted for this study is the cholinergic hypothesis. To modulate positively the cholinergic function through the inhibition of the acetylcholinesterase, a set of candidates was designed from a natural compound extracted from the cashew nutshell liquid, anacardic acid. In silico screening of this chemical library revealed a ligand that is more promising once it is correlated with an active drug through specific topological and electronic descriptors...
February 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28176635/modes-of-action-resistance-and-toxicity-of-insecticides-targeting-nicotinic-acetylcholine-receptors
#17
Makoto Ihara, Steven D Buckingham, Kazuhiko Matsuda, David B Sattelle
Nicotinic acetylcholine receptors (nAChRs) are members of the cys-loop superfamily of ligand-gated ion channels (cys-loop LGICs) and mediate fast cholinergic synaptic transmission in the nervous system of insects. The completion of many insect genome projects has greatly enhanced our understanding of the individual subunits that make up nAChR gene families from an insect genetic model organism (Drosophila melanogaster), crop pests, disease vectors and beneficial (pollinator) species. In addition to considerable insect nAChR subunit diversity, individual subunits can be subject to alternative splicing and RNA editing and these post-transcriptional modifications can add significantly to the diversity of nAChR receptor subtypes...
February 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28176016/choline-induces-opposite-changes-in-pyramidal-neuron-excitability-and-synaptic-transmission-through-a-nicotinic-receptor-independent-process-in-hippocampal-slices
#18
E Albiñana, J G Luengo, A M Baraibar, M D Muñoz, L Gandía, J M Solís, J M Hernández-Guijo
Choline is present at cholinergic synapses as a product of acetylcholine degradation. In addition, it is considered a selective agonist for α5 and α7 nicotinic acetylcholine receptors (nAChRs). In this study, we determined how choline affects action potentials and excitatory synaptic transmission using extracellular and intracellular recording techniques in CA1 area of hippocampal slices obtained from both mice and rats. Choline caused a reversible depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner that was not affected by α7 nAChR antagonists...
February 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28173798/spasmogenic-and-spasmolytic-activity-of-rind-of-punica-granatum-linn
#19
Niaz Ali, Ayesha Jamil, Syed Wadood Ali Shah, Ismail Shah, Ghayour Ahmed
BACKGROUND: Rind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range. METHODS: Rind of Punica granatum was subjected to shade drying...
February 7, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28162919/cholinergic-receptor-binding-in-alzheimer-disease-and-healthy-aging-assessment-in-vivo-with-positron-emission-tomography-imaging
#20
David L Sultzer, Rebecca J Melrose, Hannah Riskin-Jones, Theresa A Narvaez, Joseph Veliz, Timothy K Ando, Kevin O Juarez, Dylan G Harwood, Arthur L Brody, Mark A Mandelkern
OBJECTIVE: To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms. METHODS: Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied...
January 4, 2017: American Journal of Geriatric Psychiatry
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