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The Role of α7 Nicotinic Acetylcholine Receptors and α7-Specific Antibodies in Neuroinflammation Related to Alzheimer Disease.

BACKGROUND: Alzheimer disease (AD) is a neurodegenerative disorder occurring in elderly people and leading to the loss of memory, practical … cognized. OBJECTIVE: The present review aims at analysis of the role of inflammation and nicotinic acetylcholine receptors, primarily of α7 subtype (α7 nAChRs), in the development of AD in humans and AD-like symptoms in experimental animals. RESULTS: The reviewed data describe the involvement of α7 nAChRs in the AD pathogenesis, in particular, through their i …

Guidelines for standard preclinical experiments in the mouse model of myasthenia gravis induced by acetylcholine receptor immunization.

Myasthenia gravis (MG) is an autoimmune disorder characterized by generalized muscle weakness due to neuromuscular junction (NMJ) dysfunction brought by acetylcholine receptor (AChR) antibodies in most cases. Although steroids and other immunosuppressants are effectively used for treatment of MG, these medications often cause severe side effects and a complete remission cannot be obtained in many cases. For pre-clinical evaluation of more effective and less toxic treatment methods for MG, the experimental autoimmune myasthenia gravis (EAMG) induced by Torpedo AChR immunization has become one o…

Clinical Features and Diagnostic Usefulness of Antibodies to Clustered Acetylcholine Receptors in the Diagnosis of Seronegative Myasthenia Gravis.

IMPORTANCE: Cell-based assays (CBAs) were shown to improve detection of acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG). Herein, we asked whether these assays were able to help determine the diagnosis in patients studied in routine clinical practice. OBJECTIVES: To determine the diagnostic usefulness of CBAs in the diagnosis of MG and to compare the clinical features of patients with antibodies only to clustered AChRs with those of patients with seronegative MG (SNMG). DESIGN, SETTING, AND PARTICIPANTS: All patients with clinical suspicion of MG who were seen…

Effects of the Acetylcholine Release Agent ST101 with Donepezil in Alzheimer's Disease: A Randomized Phase 2 Study.

BACKGROUND AND OBJECTIVE: ST101, an acetylcholine release agent with efficacy in rodent memory and cognition models, was assessed for clinical safety and efficacy. METHODS: A phase 2 double blind, placebo-controlled study enrolled 210 AD patients (MMSE 10-20) on 10 mg donepezil QD. Patients received ST101 (10, 60, or 120 mg QD) or placebo for 12 weeks. The primary endpoint was change in cognitive function measured by ADAS-cog in the modified Intent To Treat (MITT) population and the Per Protocol (PP) population. RESULTS: Mean ADAS-cog change favored ST101 over placebo in the MITT population …

Acetylcholine produces contraction mediated by cyclooxigenase pathway in arterial vessels in the marine fish (Isacia conceptionis).

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (G. laevifrons). Our objective was to characterize the cholinergic pathway in several artery vessels of the I. conceptionis. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using doses response curves (DRC) for Ach (10(-13) to 10(-3) M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high sensitivity on…

Изучение ацетилхолинового разнообразия рецептора в нематодном паразите приводит к характеристике чувствительных к племени и дерквантель NAChR.

Никотинические ацетилхолинные рецепторы (NAChRs) паразитических нематод, необходимые для движения тела, являются объектами важных "классических" антеллиментов, таких как левамизол и пирантель, а также "новых" антеллиментов, таких как племянник и дерквантель. Four Биофизические подтипы NAChR наблюдались электрофизиологически в мышцах тела нематодового паразита Оэзофагостома, но их молекулярная основа не была понята. Кроме того, потери one подтипов (G) 35 PS) было установлено, что оно связано с сопротивлением левамизолу. В настоящем исследовании мы выявили и выразили в Ксенопус-оцитах: four О. г

Совпадение в аннотации оригинала
Nicotinic acetylcholine receptors (nAChRs) of parasitic nematodes are required for body movement and are targets of important "classical" anthelmintics like levamisole and pyrantel, as well as "novel" anthelmintics like tribendimidine and derquantel. Four biophysical subtypes of nAChR have been observed electrophysiologically in body muscle of the nematode p…

Inhibition of nicotinic acetylcholine receptors, a novel facet in the pleiotropic activities of snake venom phospholipases A2.

Phospholipases A2 represent the most abundant family of snake venom proteins. They manifest an array of biological activities, which is constantly expanding. We have recently shown that a protein bitanarin, isolated from the venom of the puff adder Bitis arietans and possessing high phospholipolytic activity, interacts with different types of nicotinic acetylcholine receptors and with the acetylcholine-binding protein. To check if this property is characteristic to all venom phospholipases A2, we have studied the capability of these enzymes from other snakes to block the responses of Lymnaea s…

[A case of prolonged neuromuscular blockade possibly related to a high anti-acetylcholine receptor antibody level].

Prolonged neuromuscular blockade is a relatively common complication of general anesthesia. Some previous reports have shown that positive serum anti-acetylcholine receptor antibody (AChR Ab) might contribute to this complication. We experienced a case of a 69-year-old woman with prolonged neuromuscular blockade after laparoscopic sigmoid colectomy under general anesthesia using rocuronium. A high level of anti-AChR Ab (45 nmol x l-1) was found in postoperative examination and the patient had progressive muscle weakness for six months after the operation. Although this patient had mediastinal …

Do acetylcholine receptor and striated muscle antibodies predict the presence of thymoma in patients with myasthenia gravis?

INTRODUCTION: Acetylcholine receptor (AChR) and striated muscle antibodies (StrAbs) are found frequently in myasthenia gravis (MG) patients with thymoma. In this study we aimed to determine the positive predictive value (PPV) and negative predictive value (NPV) of these antibodies for thymoma in patients with MG. METHODS: Antibody findings, thymic histology, and onset age were reviewed for 1141 patients with MG. PPV and NPV of these antibodies for thymoma were determined. RESULTS: The PPV of AChR binding antibodies plus StrAbs was highest (50.0%) with onset before the age of 40 years. The PP…

Dendritic spine alterations in the hippocampus and parietal cortex of alpha7 nicotinic acetylcholine receptor knockout mice.

The α7 nicotinic acetylcholine receptor (nAChR) is involved in higher cognitive and memory functions, and is associated with the etiology of neurological diseases involving cognitive decline, including Alzheimer's disease (AD). We hypothesized that spine changes in the α7 knockout might help to explain the behavioral deficits observed in α7 knockout mice and prodromal hippocampal changes in AD. We quantified several measures of dendritic morphology in the CA1 region of the mouse hippocampus in Golgi-stained material from wildtype and α7 knockout mice at P24. The most significant difference was…

Antibodies against the main immunogenic region of the acetylcholine receptor correlate with disease severity in myasthenia gravis.

OBJECTIVE: We developed an assay that detects autoantibodies against the main immunogenic region (MIR) located at the extracellular end of the nicotinic acetylcholine receptor (AChR) α subunit, and investigated its clinical relevance in myasthenia gravis (MG). METHODS: In this retrospective cohort study, we measured MIR antibody (Ab) titres in sera obtained before treatment and analysed their associations with clinical parameters in 102 MG patients from two neurological centres. MIR Ab titres were determined using a modified competition immunoprecipitation assay in the presence or absence of …

Multiple interaction regions in the orthosteric ligand binding domain of the α7 neuronal nicotinic acetylcholine receptor.

Neuronal nicotinic receptors (nAChRs) belong to the Cys-loop family of ligand-gated ion channels and are formed from five subunits either as homologous or heterologous, oligomeric receptors, and are of interest as targets for treatment of a variety of central and peripheral nervous system disorders. Using a model of the homopentameric α7 nAChR extracellular region derived from the homologous acetylcholine binding protein (AChBP) from Aplysia California, binding modes of structurally diverse, high affinity α7 ligands were examined by docking to the orthosteric ligand binding domain. While all α…

A dominant mutation in a neuronal acetylcholine receptor subunit leads to motor neuron degeneration in Caenorhabditis elegans.

Inappropriate or excessive activation of ionotropic receptors can have dramatic consequences for neuronal function and, in many instances, leads to cell death. In Caenorhabditis elegans, nicotinic acetylcholine receptor (nAChR) subunits are highly expressed in a neural circuit that controls movement. Here, we show that heteromeric nAChRs containing the acr-2 subunit are diffusely localized in the processes of excitatory motor neurons and act to modulate motor neuron activity. Excessive signaling through these receptors leads to cell-autonomous degeneration of cholinergic motor neurons and para…

A rapid, fluorescence-based assay for detecting antigenic modulation of the acetylcholine receptor on human cell lines.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease affecting approximately 40,000 patients in the United States. One of the major mechanisms of disease pathology in MG is the binding, internalization, and eventual destruction of acetylcholine receptors (AChR) at the neuromuscular junction by cross-linking AChR-specific autoantibodies. This process, known as antigenic modulation, ultimately attenuates the ability of muscle cells to contract in response to signals from neurons, leading to muscle weakness and fatigue. For this reason, antigenic modulation of the AChR on cultured cells ha…

The impact of hypoxia and low glucose on the release of acetylcholine and ATP from the incubated cat carotid body.

The carotid body (CB) is a polymodal sensor which increases its neural output to the nucleus tractus solitarii with a subsequent activation of several reflex cardiopulmonary responses. Current reports identify acetylcholine (ACh) and adenosine triphosphate (ATP) as two essential excitatory neurotransmitters in the cat and rat CBs. This study explored the impact of hypoxia, low glucose, and the two together on the release of both ACh and ATP from two incubated cat CBs. The CBs were prepared with standard procedures in accordance with the policies and regulations of the Institutional Animal Care…

[Anesthetic considerations for thymectomy in a patient having an anti-acetylcholine receptor antibody without myasthenia gravis].

A patient having an anti-acetylcholine receptor (AChR) antibody without myasthenia gravis was scheduled for thymectomy. Neuromuscular blockade monitoring showed a normal response to vecuronium in the patient. This finding suggests that sensitivities to neuromuscular blocking agents in the patients depend not on the titers of the antibody but also on the presence or absence of the preoperative symptoms such as muscle weakness. It is, however, recommended that neuromuscular blocking agents should be administered carefully under monitoring the neuromuscular function, as is the case for myasthenia…

Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic acetylcholine receptors in vivo and in vitro.

The pathogenesis of chagasic cardiomyopathy is not completely understood, but it has been correlated with parasympathetic denervation (neurogenic theory) and inflammatory activity (immunogenic theory) that could affect heart muscarinic acetylcholine receptor (mAChR) expression. In order to further understand whether neurogenic and/or immunogenic alterations are related to changes in mAChR expression, we studied two models of Trypanosoma cruzi infection: 1) in 3-week-old male Sprague Dawley rats chronically infected with T. cruzi and 2) isolated primary cardiomyocytes co-cultured with T. cruzi …

Hydrogen-bond interactions of nicotine and acetylcholine salts: a combined crystallographic, spectroscopic, thermodynamic and theoretical study.

The hydrogen-bond (HB) interactions of the monocharged active forms of nicotine and acetylcholine (ACh) have been compared theoretically by using density functional theory (DFT) calculations and experimentally on the basis of crystallographic observations and the measurement of equilibrium constants in solution. The 2,4,6-trinitrophenolate (picrate) counterion was used to determine the experimental HB basicity of the cations despite its potential multisite HB acceptor properties. The preferred HB interaction site of the ammonium picrate salts was determined from a survey of crystallographic da…