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The important role of Acetylcholine

Katrin Richter, Sabrina Sagawe, Andreas Hecker, Mira Küllmar, Ingolf Askevold, Jelena Damm, Sarah Heldmann, Michael Pöhlmann, Sophie Ruhrmann, Michael Sander, Klaus-Dieter Schlüter, Sigrid Wilker, Inke R König, Wolfgang Kummer, Winfried Padberg, Arik J Hone, J Michael McIntosh, Anna Teresa Zakrzewicz, Christian Koch, Veronika Grau
Blood levels of the acute phase reactant C-reactive protein (CRP) are frequently measured as a clinical marker for inflammation, but the biological functions of CRP are still controversial. CRP is a phosphocholine (PC)-binding pentraxin, mainly produced in the liver in response to elevated levels of interleukin-1β (IL-1β) and of the IL-1β-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1β levels can cause life-threatening diseases such as trauma-associated systemic inflammation...
2018: Frontiers in Immunology
Carla Roberta Nunes Polachini, Roselia Maria Spanevello, Maria Rosa Chitolina Schetinger, Vera Maria Morsch
Multiple sclerosis (MS) commonly affects young adults and leads to a decreased quality of life due to different signs and symptoms that induce physical, cognitive, social, and psychological challenges. This disease, an autoimmune neurological disorder, is characterized by chronic inflammatory demyelination and axonal degeneration of the central nervous system (CNS). To date, its etiology is unknown. A large number of physiological functions are regulated by the cholinergic system because the acetylcholine (ACh) is released from cholinergic neurons and acts on other neurons, most of them not cholinergic in the brain, as well as in various nonneuronal cells, such as those of the immune system and blood; thus, it is considered an important modulatory pathway of both the central and peripheral nervous systems...
September 15, 2018: Journal of the Neurological Sciences
Mia L Huang, Ember M Tota, Taryn M Lucas, Kamil Godula
Achieving molecular control over the formation of synaptic contacts in the nervous system can provide important insights into their regulation and can offer means for creating well-defined in vitro systems to evaluate modes of therapeutic intervention. Agrin-induced clustering of acetylcholine receptors (AChRs) at postsynaptic sites is a hallmark of the formation of the neuromuscular junction, a synapse between motoneurons and muscle cells. In addition to the cognate agrin receptor, LRP4 (low-density lipoprotein receptor related protein-4), muscle cell surface heparan sulfate (HS) glycosaminoglycans (GAGs) have been proposed to contribute to AChR clustering by acting as agrin co-receptors...
August 10, 2018: ACS Chemical Neuroscience
Linmei Zheng, Lei Shi, Zhongyi Zhou, Xiaoju Chen, Li Wang, Zhicheng Lu, Rong Tang
OBJECTIVES: This study aimed to investigate placental expression of AChE, α7nAChR and NF-κB in patients with preeclampsia and discuss about its clinical significance. MATERIAL AND METHODS: mRNA expression levels of acetylcholine (AChE), alpha-7 nicotinic acetylcholine receptor (α7nAChR) and nuclear factor-kB (NF-κB) in placenta were detected by qRT-PCR, and protein levels were determined by immunohis-tological analysis and Western Blot in 35 women with preeclampsia (including 20 cases of mild preeclampsia and 15 cases of severe preeclampsia) and 30 cases in control group, respectively...
2018: Ginekologia Polska
Satoe Takahashi, Willy Sun, Yingjie Zhou, Kazuaki Homma, Bechara Kachar, Mary Ann Cheatham, Jing Zheng
Outer hair cells (OHC) act as amplifiers and their function is modified by medial olivocochlear (MOC) efferents. The unique OHC motor protein, prestin, provides the molecular basis for somatic electromotility, which is required for sensitivity and frequency selectivity, the hallmarks of mammalian hearing. Prestin proteins are the major component of the lateral membrane of mature OHCs, which separates apical and basal domains. To investigate the contribution of prestin to this unique arrangement, we compared the distribution of membrane proteins in OHCs of wildtype (WT) and prestin-knockout (KO) mice...
2018: Frontiers in Cellular Neuroscience
Nair Olguín, Marie-Lena Müller, Eduard Rodríguez-Farré, Cristina Suñol
Methylmercury (MeHg) is an environmental toxicant with detrimental effects on the developing brain and adult nervous system. The main mechanisms identified include oxidative stress, changes in intracellular calcium, mitochondrial changes, inhibition of glutamate uptake, of protein synthesis and disruption of microtubules. However, little is known about mechanisms of protection against MeHg neurotoxicity. We found that resveratrol (10µM) and ascorbic acid (200µM) protected MeHg-induced cell death in primary cultures of cortical neurons...
July 31, 2018: Neurotoxicology
Chunhua Wan, Miaomiao Wu, Shusen Zhang, Yuyan Chen, Cuihua Lu
The cholinergic signaling pathways have been recently implicated in the development of various human cancers. However, the underlying molecular mechanism remains largely unclear. In the present study, we reported that α7 nicotinic acetylcholine receptor (α7nAChR), an important member of nicotinic acetylcholine receptors, interacts with Protein Phosphatase-1γ (PP1γ) in human Hepatocellular Carcinoma (HCC) tissues. In addition, we found that α7nAChR facilitates the ubiquitination and activation of TRAF6 in a PP1γ-dependent manner in HCC cells...
August 3, 2018: Molecular Carcinogenesis
Mei Huang, Sunoh Kwon, Lakshmi Rajagopal, Wenqi He, Herbert Y Meltzer
RATIONALE: The effect of atypical antipsychotic drugs (AAPDs), e.g., lurasidone, to improve cognitive impairment associated with schizophrenia (CIAS), has been suggested to be due, in part, to enhancing release of dopamine (DA), acetylcholine (ACh), and glutamate (Glu) in cortex and hippocampus. RESULTS: The present study found acute lurasidone reversed the cognitive deficit in novel object recognition (NOR) in subchronic (sc) phencyclidine (PCP)-treated mice, an animal model for CIAS...
July 31, 2018: Psychopharmacology
Marieke Jepma, Stephen B R E Brown, Peter R Murphy, Stephany C Koelewijn, Boukje de Vries, Arn M van den Maagdenberg, Sander Nieuwenhuis
To make optimal predictions in a dynamic environment, the impact of new observations on existing beliefs-that is, the learning rate-should be guided by ongoing estimates of change and uncertainty. Theoretical work has proposed specific computational roles for various neuromodulatory systems in the control of learning rate, but empirical evidence is still sparse. The aim of the current research was to examine the role of the noradrenergic and cholinergic systems in learning rate regulation. First, we replicated our recent findings that the centroparietal P3 component of the EEG-an index of phasic catecholamine release in the cortex-predicts trial-to-trial variability in learning rate and mediates the effects of surprise and belief uncertainty on learning rate (Study 1, N = 17)...
July 31, 2018: Journal of Cognitive Neuroscience
Aaron L Nichols, Kaori Noridomi, Chris R Hughes, Farzad Jalali-Yazdi, J Brek Eaton, Lan Huong Lai, Gaurav Advani, Ronald J Lukas, Henry A Lester, Lin Chen, Richard W Roberts
The nicotinic acetylcholine receptors are pentameric ligand-gated ion channels that play a central role in neuronal and neuromuscular signal transduction. Here, we have developed FANG ligands - Fibronectin Antibody-mimetic Nicotinic acetylcholine receptor Generated ligands - using mRNA display. We generated a trillion-member primary e10FnIII library to target a stabilized α1 nicotinic subunit (α211). This library yielded 270,000 independent potential protein-binding ligands. The lead sequence, α1-FANG1, represented 25% of all library sequences, showed the highest-affinity binding, and competed with α-bungarotoxin (α-Btx)...
July 30, 2018: ACS Chemical Biology
Constantine Farmakidis, Mamatha Pasnoor, Richard J Barohn, Mazen M Dimachkie
PURPOSE OF REVIEW: Congenital myasthenia syndromes are clinically and genetically heterogeneous but treatable conditions. Careful selection of drug therapy is paramount as the same drug can be effective, ineffective, and even harmful in different congenital myasthenia syndromes. The purpose of this article is to review current treatment options for these conditions. RECENT FINDINGS: Next-generation sequencing has accelerated the discovery of new genes and facilitated the description of novel congenital myasthenic syndromes...
July 21, 2018: Current Treatment Options in Neurology
Melissa Verkaik, Rio P Juni, Ellen P M van Loon, Erik van Poelgeest, Rick F J Kwekkeboom, Zeineb Gam, William G Richards, Pieter M Ter Wee, Joost G J Hoenderop, Etto C Eringa, Marc G Vervloet
BACKGROUND: Cardiovascular diseases account for approximately 50% of mortality in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) is independently associated with endothelial dysfunction and cardiovascular mortality. We hypothesized that CKD impairs microvascular endothelial function and that this can be attributed to FGF23. METHODS: Mice were subjected to partial nephrectomy (5/6Nx) or sham-surgery. To evaluate the functional role of FGF23, non-CKD mice received FGF23 injections, and CKD mice received FGF23 blocking antibodies following 5/6Nx surgery...
July 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Nargis Tabassum, Han-Shen Tae, Xinying Jia, Quentin Kaas, Tao Jiang, David J Adams, Rilei Yu
α-Conotoxins preferentially antagonize muscle and neuronal nicotinic acetylcholine receptors (nAChRs). Native α-conotoxins have two disulfide links, CI -CIII and CII -CIV , and owing to the inherent properties of disulfide bonds, α-conotoxins have been systematically engineered to improve their chemical and biological properties. In this study, we explored the possibility of simplifying the disulfide framework of α-conotoxins Vc1.1, BuIA, ImI, and AuIB, by introducing [C2H,C8F] modification to the CI -CIII bond...
August 31, 2017: ACS Omega
Hyunjin Kim, Young-Min Lim, Eun-Jae Lee, Yeo Jin Oh, Kwang-Kuk Kim
INTRODUCTION: Although thymectomy is an important therapeutic option for myasthenia gravis (MG), factors predicting remission after thymectomy are not well known. METHODS: We retrospectively reviewed acetylcholine receptor antibody (AChR-Ab)-positive MG patients who had undergone thymectomy. Prognostic factors predicting remission were investigated. Changes in AChR-Ab titer before and after thymectomy were also evaluated. RESULTS: Among the 179 patients, 52...
July 18, 2018: Muscle & Nerve
Miao Jing, Peng Zhang, Guangfu Wang, Jiesi Feng, Lukas Mesik, Jianzhi Zeng, Huoqing Jiang, Shaohua Wang, Jess C Looby, Nick A Guagliardo, Linda W Langma, Ju Lu, Yi Zuo, David A Talmage, Lorna W Role, Paula Q Barrett, Li I Zhang, Minmin Luo, Yan Song, J Julius Zhu, Yulong Li
The neurotransmitter acetylcholine (ACh) regulates a diverse array of physiological processes throughout the body. Despite its importance, cholinergic transmission in the majority of tissues and organs remains poorly understood owing primarily to the limitations of available ACh-monitoring techniques. We developed a family of ACh sensors (GACh) based on G-protein-coupled receptors that has the sensitivity, specificity, signal-to-noise ratio, kinetics and photostability suitable for monitoring ACh signals in vitro and in vivo...
July 9, 2018: Nature Biotechnology
Krystyna Makowska, Liliana Rytel, Piotr Lech, Adam Osowski, Ewa Kruminis-Kaszkiel, Slawomir Gonkowski
Cocaine- and amphetamine-regulated transcript peptide (CART) is widely distributed within the central and peripheral nervous system. In the brain, CART is considered as the main anorectic peptide involved in the regulation of food intake. Contrary to the central nervous system, a lot of aspects connected with the distribution and functions of CART within the enteric nervous system (ENS) still remain unknown. The aim of the present study was to investigate, for the first time, the population of CART-like immunoreactive (CART-LI) neurons within the porcine esophagus and the denotation of their neurochemical coding...
July 2018: Comptes Rendus Biologies
Tomoyuki Ono, Munenori Nagao, Hirofumi Imoto, Kazuhiro Watanabe, Naoki Tanaka, Fuyuhiko Motoi, Takeshi Naitoh, Michiaki Unno
BACKGROUND: Although intra-arterial infusion of calcitonin gene-related peptide (CGRP) reportedly stimulates giant migrating contractions (GMCs) of the small intestine in conscious dogs, the effect of intravenous CGRP administration on colonic motility remains unclear. In the present study, we investigated the effects of intravenous CGRP on colonic motility and defecation and determined the underlying mechanism of action in conscious dogs. METHODS: Sixteen Beagle dogs weighing 11-13 kg were included...
July 6, 2018: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
Fang Qiu, Xiaodong Liu, Yanyan Zhang, Ying Wu, Daliao Xiao, Lijun Shi
Melatonin, a neuroendocrine hormone synthesized primarily by the pineal gland, provides various cardiovascular benefits. Regular physical activity is an effective non-pharmacological therapy for the prevention and control of hypertension. In the present study, we hypothesized that melatonin plays an important role in the aerobic exercise-induced increase of endothelium-dependent vasorelaxation in the mesenteric arteries (MAs) of spontaneously hypertensive rats (SHRs) in a melatonergic receptor-dependent manner...
July 2, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Lin-Hui Ni, Shu-Xia Cao, Hong Lian, Xing-Yue Hu
The central cholinergic nervous system plays an important role in cognition, with acetylcholine hypofunction considered to be a major factor of dementia. Botulinum toxin type A (BoNT/A), a potent poison secreted by Clostridium botulinum, is used widely for dystonia treatment and facial cosmesis. BoNT/A injection inhibits acetylcholine release in the neuromuscular junction through cleavage of synaptosomal-associated protein of 25 kDa in cholinergic terminals. Furthermore, beyond the injection site, BoNT/A undergoes retrograde transport and transcytosis to the central nervous system from peripheral cholinergic terminals...
August 15, 2018: Neuroreport
Kateryna Uspenska, Olena Lykhmus, Maria Obolenskaya, Stephanie Pons, Uwe Maskos, Serhiy Komisarenko, Maryna Skok
Nicotinic acetylcholine receptors (nAChRs) expressed on the cell plasma membrane are ligand-gated ion channels mediating fast synaptic transmission, regulating neurotransmitter and cytokine release and supporting the viability of many cell types. The nAChRs expressed in mitochondria regulate the release of pro-apoptotic factors, like cytochrome c , in ion channel-independent manner. Here we show that α3β2, α7β2, and α9α10 nAChR subtypes are up-regulated in rat liver mitochondria 3-6 h after partial hepatectomy resulting in increased sustainability of mitochondria to apoptogenic effects of Ca2+ and H2 O2 ...
2018: Frontiers in Pharmacology
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