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Baseline acetylcholine levels

Magdalena König, Beata Berlin, Karima Schwab, Silke Frahm, Franz Theuring, Claude M Wischik, Charles R Harrington, Gernot Riedel, Jochen Klein
Pathological accumulation of misfolded α-synuclein (α-syn) in the brain plays a key role in the pathogenesis of Parkinson's disease, leading to neuronal dysfunction and motor disorders. The underlying mechanisms linking α-syn aggregations with neurotransmitter disturbance in Parkinson's brains are not well characterized. In the present study, we investigated transgenic mice expressing an aggregation-prone form of full-length human α-syn (h-α-synL62) linked to a signal sequence. These mice display dopamine depletion and progressive motor deficits...
September 28, 2018: ACS Chemical Neuroscience
Richard L Verrier, Alexandre L Bortolotto, Bruna A Silva, Alexandre A Marum, Fernando G Stocco, Ederson Evaristo, Victor Z de Antonio, Anderson C Silva, Luiz Belardinelli
BACKGROUND: Pulmonary delivery of antiarrhythmic agents has the potential to increase rapidly targeted drug concentrations in pulmonary veins and left atrium to terminate atrial fibrillation (AF). OBJECTIVE: We evaluated the efficacy of flecainide administered via intratracheal instillation in terminating AF in a reliable preclinical model. METHODS: In 11 closed-chest anesthetized Yorkshire pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of 102...
June 26, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Syeda Mehpara Farhat, Touqeer Ahmed
BACKGROUND: Aluminum (Al) causes neurodegeneration and its toxic effects on cholinergic system in the brain is well documented. However, it is unknown whether and how Al changes oscillation patterns, driven by the cholinergic system, in the hippocampus. OBJECTIVE: We studied acute effects of Al on nicotinic acetylcholine receptors (nAChRs)-mediated modulation of persistent gamma oscillations in the hippocampus. METHOD: The field potential recording was done in CA3 area of acute hippocampal slices...
2018: CNS & Neurological Disorders Drug Targets
Ashley A Martin, Janet E Richmond
Nicotinic acetylcholine receptors (nAChR) are present in many excitable tissues and are found both pre and post-synaptically. Through their non-specific cationic permeability, these nAChRs have excitatory roles in neurotransmission, neuromodulation, synaptic plasticity, and neuroprotection. Thus, nAChR mislocalization or functional deficits are associated with many neurological disease states. Therefore identifying the mechanisms that regulate nAChR expression and function will inform our understanding of normal as well as pathological physiological conditions and offer avenues for potential therapeutic advances...
June 2018: Cell Calcium
Ba H Do, Toyoaki Ohbuchi, Tetsuro Wakasugi, Hiroki Koizumi, Mitsuru Yokoyama, Nobusuke Hohchi, Hideaki Suzuki
Background Airway mucociliary transport is an important function for the clearance of inhaled foreign particulates in the respiratory tract. The present study aimed at investigating the regulatory mechanism of acetylcholine (Ach)-induced ciliary beat of the human nasal mucosa in ex vivo. Methods The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic surgery. The mucosa was cut into thin strips, and ciliary movement was observed under a phase-contrast light microscope with a high-speed digital video camera...
July 2018: American Journal of Rhinology & Allergy
Karen Hewett, Donald B Sanders, Richard A Grove, Christine L Broderick, Todd J Rudo, Ashlyn Bassiri, Marina Zvartau-Hind, Vera Bril
OBJECTIVE: To investigate the efficacy and safety of belimumab, a fully human immunoglobulin G1λ monoclonal antibody against B-lymphocyte stimulator, in participants with generalized myasthenia gravis (MG) who remained symptomatic despite standard of care (SoC) therapy. METHODS: Eligible participants with MG were randomized 1:1 to receive IV belimumab 10 mg/kg or placebo in this phase II, placebo-controlled, multicenter, double-blind study (NCT01480596; BEL115123)...
April 17, 2018: Neurology
Y S Qian, Q Y Zhao, S J Zhang, Y J Zhang, Y C Wang, H Y Zhao, Z X Dai, Y H Tang, X Wang, T Wang, C X Huang
Objective: To investigate the effect of α7nAChR mediated cholinergic anti-inflammatory pathway on inhibition of atrial fibrillation by low-level vagus nerve stimulation(LL-VNS). Methods: Eighteen beagles were randomized into control group ( n =6), LL-VNS group ( n =6) and methyllycaconitine (MLA) + LL-VNS group ( n =6). All the beagles were subjected to rapid atrial pacing at 800 beats/min for 6 hours.And the effective refractory period (ERP) of atriums and pulmonary veins and induced atrial fibrillation (AF) were measured hourly during non-pacing...
March 20, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Tiziana Cappello, Alessia Giannetto, Vincenzo Parrino, Maria Maisano, Sabrina Oliva, Giuseppe De Marco, Giulia Guerriero, Angela Mauceri, Salvatore Fasulo
The Mediterranean mussel Mytilus galloprovincialis (Lamarck 1819) is a popular shellfish commonly included in human diet and is routinely used as bioindicator in environmental monitoring programmes worldwide. Recently, metabolomics has emerged as a powerful tool both in food research and ecotoxicology for monitoring mussels' freshness and assessing the effects of environmental changes. However, there is still a paucity of data on complete metabolic baseline of mussel tissues. To mitigate this knowledge gap, similarities and differences in metabolite profile of digestive gland (DG), gills (G), and posterior adductor muscle (PAM) of aquaculture-farmed M...
June 2018: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Carl Johan Molin, Liis Sabre, Cleo-Aron Weis, Tanel Punga, Anna Rostedt Punga
Objective: The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels. Methods: Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment...
May 2018: Neurology® Neuroimmunology & Neuroinflammation
Brice Ongali, Nektaria Nicolakakis, Xin-Kang Tong, Clotilde Lecrux, Hans Imboden, Edith Hamel
Transgenic mice constitutively overexpressing the cytokine transforming growth factor-β1 (TGF-β1) (TGF mice) display cerebrovascular alterations as seen in Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID), but no or only subtle cognitive deficits. TGF-β1 may exert part of its deleterious effects through interactions with angiotensin II (AngII) type 1 receptor (AT1R) signaling pathways. We test such interactions in the brain and cerebral vessels of TGF mice by measuring cerebrovascular reactivity, levels of protein markers of vascular fibrosis, nitric oxide synthase activity, astrogliosis, and mnemonic performance in mice treated (6 months) with the AT1R blocker losartan (10 mg/kg per day) or the angiotensin converting enzyme inhibitor enalapril (3 mg/kg per day)...
May 2018: Canadian Journal of Physiology and Pharmacology
Nobuaki Egashira, Yuki Akiyoshi, Hikari Iba, Takashi Arai, Izzettin Hatip-Al-Khatib, Kenichi Mishima, Katsunori Iwasaki
Previously, we reported that ovariectomy (OVX) combined with β-amyloid peptide (Aβ) impaired spatial memory by decreasing extracellular acetylcholine (ACh) levels in the dorsal hippocampus. Here, we investigated the effect of tokishakuyakusan (TSS), a Kampo medicine, on the impairment of spatial memory induced by OVX combined with Aβ in rats. Repeated administration of TSS (300 mg/kg, p.o.) significantly decreased the number of errors in the eight-arm radial maze test. Though TSS had no effect on extracellular ACh levels at baseline, TSS significantly increased extracellular ACh levels in the dorsal hippocampus...
March 2018: Journal of Pharmacological Sciences
Hilary S McCarren, Julia A Arbutus, Cherish Ardinger, Emily N Dunn, Cecelia E Jackson, John H McDonough
Nerve agents are highly toxic chemicals that pose an imminent threat to soldiers and civilians alike. Nerve agent exposure leads to an increase in acetylcholine within the central nervous system, resulting in development of protracted seizures known as status epilepticus (SE). Currently, benzodiazepines are the standard of care for nerve agent-induced SE, but their efficacy quickly wanes as the time to treatment increases. Here, we examine the role of the α2-adrenoceptor in termination of nerve agent-induced SE using the highly specific agonist dexmedetomidine (DEX)...
March 2018: Epilepsy Research
Walter Roberts, Sherry A McKee
Varenicline reduces drinking in people with alcohol use disorder, but little is known about the mechanisms underlying this effect. Varenicline targets α4β2 and α7 nicotinic acetylcholine receptors, which are associated with several cognitive functions such as working memory. Varenicline may improve drinking outcomes by enhancing cognitive functioning. The current manuscript reports on cognitive outcomes from a placebo-controlled, double-blind human laboratory experiment examining the effects of varenicline on drinking behavior (Verplaetse et al...
February 2018: Experimental and Clinical Psychopharmacology
Marko Stupin, Ana Stupin, Lidija Rasic, Anita Cosic, Luka Kolar, Vatroslav Seric, Helena Lenasi, Kresimir Izakovic, Ines Drenjancevic
PURPOSE: The effect of acute exhaustive exercise session on skin microvascular reactivity was assessed in professional rowers and sedentary subjects. A potential involvement of altered hemodynamic parameters and/or oxidative stress level in the regulation of skin microvascular blood flow by acute exercise were determined. METHODS: Anthropometric, biochemical, and hemodynamic parameters were measured in 18 young healthy sedentary men and 20 professional rowers who underwent a single acute exercise session...
February 2018: European Journal of Applied Physiology
Qing Qin, Silvia Delrio, Junxiang Wan, R Jay Widmer, Pinchas Cohen, Lilach O Lerman, Amir Lerman
BACKGROUND: MOTS-c is one of the newly identified mitochondrial-derived peptides which play a role in regulating metabolic homeostasis. The current study aimed to investigate whether circulating MOTS-c levels are also associated with endothelial dysfunction(ED) in patients without significant structural coronary lesions. METHODS: Forty patients undergoing coronary angiography and endothelial function testing for clinical indications of recurrent angina with no structural coronary lesions were included in the study...
March 1, 2018: International Journal of Cardiology
Alessandra S M Matheus, Maria de Fátima B da Matta, Eliete Leão S Clemente, Maria de Lourdes G Rodrigues, Débora Cristina T Valença, Marília B Gomes
OBJECTIVES: To find out an normality value for microvascular response (physiological and pharmacological) assessed through laser speckle contrast imaging (LSCI) based on Endo-PAT, which identifies the ones with Endothelial Dysfunction (ED) in patients with Type 1 Diabetes (T1D). METHODS: Patients with T1D, aged ≥12years underwent a clinical-epidemiological questionnaire. Fasting blood samples were obtained (lipid profile, glycemic control and levels of C-reactive protein)...
May 2018: Microvascular Research
Seung-Ryeol Lee, Ki-Ho Kim, Ho-Song You, Johnny Fu, Tung-Chin Mike Hsieh, Valmik Bhargava, M Raj Rajasekaran
Current technology for penile hemodynamic evaluations in small animals is invasive and has limitations. We evaluated a novel laser speckle contrast imaging (LSCI) technique to determine age-related changes in penile microvascular perfusion (PMP) and tested the role of cavernosal muscle (CC) fibrosis mediated by Wnt-TGF β 1 signaling pathways in a mouse model. Ten young (2-3 months) and old (24-28 months) wild-type C57BL6 male mice were subjected to PMP measured using a LSCI system. Penile blood flow (PBF, peak systolic velocity, PSV) was also measured using a color Doppler ultrasound for comparison...
November 2017: Physiological Reports
Kyle K Pitchers, Louisa F Kane, Youngsoo Kim, Terry E Robinson, Martin Sarter
Discrete Pavlovian reward cues acquire more potent incentive motivational properties (incentive salience) in some animals (sign-trackers; STs) compared to others (goal-trackers; GTs). Conversely, GTs appear to be better than STs in processing more complex contextual cues, perhaps reflecting their relatively greater bias for goal-directed cue processing. Here, we investigated the activity of two major prefrontal neuromodulatory input systems, dopamine (DA) and acetylcholine (ACh), in response to a discrete Pavlovian cue that was previously paired with cocaine administration in STs and GTs...
December 2017: European Journal of Neuroscience
Luis M Carcoba, Rodolfo J Flores, Luis A Natividad, Laura E O'Dell
The aversive effect of nicotine withdrawal is greater in female versus male rats, and we postulate that this sex difference is mediated in the nucleus accumbens (NAc). Nicotine withdrawal induces decreases in NAc dopamine and increases in acetylcholine (ACh) levels in male rats. To our knowledge, these neurochemical markers of nicotine withdrawal have not been compared in female versus male rats. Given the role of amino acids in modulating NAc dopaminergic and cholinergic transmission, concomitant measures of gamma-aminobutyric acid (GABA) and glutamate levels were also compared across sex...
September 22, 2017: Addiction Biology
Morten Matthiesen Bach Damm, Thorbjørn Søren Rønn Jensen, Badar Mahmood, Morten Lundh, Steen Seier Poulsen, Niels Bindslev, Mark Berner Hansen
The pathogenesis of colorectal neoplasia (CRN) has been associated with altered non-neuronal acetylcholine (ACh) metabolism. The aim of this study was to characterize expression, function, and cellular location of ACh-related proteins in biopsies obtained from endoscopic normal-appearing sigmoid colon in patients with and without CRN. Messenger-RNA (mRNA) levels of 17 ACh-related proteins were quantified by rt-qPCR. Functional responses to ACh, measured as electrogenic transepithelial short circuit current (SCC), were recorded using the Ussing chamber technique...
October 2017: Molecular Carcinogenesis
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