nicotine neuromuscular

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from loss of upper and lower motor neurons in the brain and spinal cord. Due to the unknown etiology of sporadic ALS (SALS), interventions that are neuroprotective are urgently needed. Evidence shows that caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding and neuroprotective protein, is decreased in degenerating neurons along with Cav-1-associated pro-survival signaling proteins. We have previously shown that synapsin-promoted Cav-1 (SynCav1) augments neuroplasticity, preserves synaptic ultrastructure and hippocampal learning and memory in a mouse model of Alzheimer's disease...

The presence of autoantibodies directed against the muscle nicotinic acetylcholine receptor (AChR) is the most common cause of myasthenia gravis (MG). These antibodies damage the postsynaptic membrane of the neuromuscular junction and cause muscle weakness by depleting AChRs and thus impairing synaptic transmission. As one of the best-characterized antibody-mediated autoimmune diseases, AChR-MG has often served as a reference model for other autoimmune disorders. Classical pharmacological treatments, including broad-spectrum immunosuppressive drugs, are effective in many patients...

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies targeting components of the postsynaptic membrane of the neuromuscular junction (NMJ), leading to neuromuscular transmission deficiency. In the vast majority of patients, these autoantibodies target the nicotinic acetylcholine receptor (nAChR), a heteropentameric ion channel anchored to the postsynaptic membrane of the NMJ. Autoantibodies in patients with MG may target all the subunits of the receptor at both their extracellular and intracellular regions...

Lynx1 is a glycosylphosphatidylinositol (GPI)-linked protein shown to affect synaptic plasticity through modulation of nicotinic acetylcholine receptor (nAChR) subtypes in the brain. Because of this function and structural similarity to α-bungarotoxin, which binds muscle-specific nAChRs with high affinity, Lynx1 is a promising candidate for modulating nAChRs in skeletal muscles. However, little is known about the expression and roles of Lynx1 in skeletal muscles and neuromuscular junctions (NMJs). Here, we show that Lynx1 is expressed in skeletal muscles, increases during development, and concentrates at NMJs...

The role of α7 nicotinic acetylcholine receptors in coupling of synaptic activity and muscle contractions was studied in frog (Rana ridibunda) neuromuscular synapses. The amplitude of endplate currents, the probability of action potential generation, and the strength of muscle contractions decreased in the presence of selective α7 antagonist methyllycaconitine. The effects of nicotinic acetylcholine receptor blockade depended on the pattern of the motor nerve stimulation. It can be assumed that the muscle action potential is a factor of retrograde control of neurosecretion, which modulates activity of α7 nicotinic receptors and the release of acetylcholine from motor nerve endings...

Myasthenia gravis is a chronic autoimmune disease characterized by autoantibody-mediated interference of signal transmission across the neuromuscular junction. We performed a genome-wide association study (GWAS) involving 1,873 patients diagnosed with acetylcholine receptor antibody-positive myasthenia gravis and 36,370 healthy individuals to identify disease-associated genetic risk loci. Replication of the discovered loci was attempted in an independent cohort from the UK Biobank. We also performed a transcriptome-wide association study (TWAS) using expression data from skeletal muscle, whole blood, and tibial nerve to test the effects of disease-associated polymorphisms on gene expression...

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease that is associated with the production of autoantibodies. The symptoms of MG are mainly mediated by pathogenic antibodies directed against nicotinic acetylcholine receptors, resulting in a decrease in the number of acetylcholine receptors molecules on the postsynaptic membrane of the neuromuscular junction endplate, leading to clinical symptoms of muscle fatigue and weakness. At present, traditional Chinese medicine (TCM) treatment of MG has a better effect by tonifying spleen and replenishing qi...

C-shapes are stereotyped movements in planarians that are elicited by diverse stimuli (e.g. acidity, excitatory neurotransmitters, psychostimulants, and pro-convulsants). Muscle contraction and seizure contribute to the expression of C-shape movements, but a causative role for pain is understudied and unclear. Here, using nicotine-induced C-shapes as the endpoint, we tested the efficacy of three classes of antinociceptive compounds - an opioid, NSAID (non-steroidal anti-inflammatory drug), and transient receptor potential ankyrin 1 (TRPA1) channel antagonist...

Sulfoxaflor is an insecticide belonging to the recent sulfoximine class, acting as a nicotinic acetylcholine receptor (nAChRs) agonist. There are few studies regarding sulfoxaflor's toxicity to non-target organisms. The present study aimed to investigate the acute and sub-lethal effects of sulfoxaflor on Carcinus maenas by addressing survival, behaviour (feed intake and motricity), and neuromuscular, detoxification and oxidative stress, and energy metabolism biomarkers. Adult male green crabs were exposed to sulfoxaflor for 96 h and an LC50 of 2...

Huntington's disease (HD) causes neurological impairments, as well as muscle dysfunction, including smaller neuromuscular junctions (NMJs). This study assessed the expression levels of the subunits of the nicotinic acetylcholine receptor (nAChR) in muscles of the R6/2 mouse model of HD. Based on our previous findings of reduced NMJ size in R6/2 mice, it was hypothesized that muscles from R6/2 mice would also show an altered expression pattern of nAChR subunits compared to wild-type (WT) mice. Therefore, the mRNA levels of nAChR subunits were quantified in R6/2 and WT mouse muscles using qRT-PCR...

Myasthenia gravis (MG) is a chronic and progressive neuromuscular disease where autoantibodies target essential proteins such as the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction (NMJ) causing muscle fatigue and weakness. Autoantibodies directed against nAChRs are proposed to work by three main pathological mechanisms of receptor disruption: blocking, receptor internalization, and downregulation. Current in vivo models using experimental autoimmune animal models fail to recapitulate the disease pathology and are limited in clinical translatability due to disproportionate disease severity and high animal death rates...

Complex biological functions within organisms are frequently orchestrated by systemic communication between tissues. In the model organism Caenorhabditis elegans, the pharyngeal and body wall neuromuscular junctions are two discrete structures that control feeding and locomotion, respectively. Separate, the well-defined neuromuscular circuits control these distinct tissues. Nonetheless, the emergent behaviors, feeding and locomotion, are coordinated to guarantee the efficiency of food intake. Here, we show that pharmacological hyperactivation of cholinergic transmission at the body wall muscle reduces the rate of pumping behavior...

Intentional ingestion of agricultural organophosphorus insecticides is a significant public health issue in rural Asia, causing thousands of deaths annually. Some survivors develop a severe, acute or delayed myasthenic syndrome. In animal models, similar myasthenia has been associated with increasing plasma concentration of one insecticide solvent metabolite, cyclohexanol. We investigated possible mechanisms using voltage and current recordings from mouse neuromuscular junctions (NMJs) and transfected human cell lines...

Nicotinic acetylcholine receptors (nAchRs) are widely distributed within the nervous system across most animal species. Besides their well-established roles in mammalian neuromuscular junctions, studies using invertebrate models have also proven fruitful in revealing the function of nAchRs in the central nervous system. During the earlier years, both in vitro and animal studies had helped clarify the basic molecular features of the members of the Drosophila nAchR gene family and illustrated their utility as targets for insecticides...

Nicotinic acetylcholine receptors (nAChRs) comprise a large and ancient family of allosteric ion channels mediating synaptic transmission. The vast knowledge about nAChRs has become difficult to navigate. NAChRDB is a web-accessible resource of curated residue-level functional annotations of neuromuscular nAChRs. Interactive three-dimensional (3D) visualization and sequence alignment give further context to this rich and growing collection of experimental observations and computational predictions. NAChRDB is freely available at https://crocodile...

The depolarization of the postsynaptic membrane potential in neuromuscular junction, which is conducted by the (stochastic) opening of nicotinic acetylcholine (nACh) receptors distributed in postsynaptic folds, is an inevitable stage in transmitting the electric signals from neural ends to muscle fibers. To perform this work, free energy must be dissipated. Being the first step in understanding the speech-accuracy-energy trade-off, we calculate the energy dissipation of a tiny membrane system that contains a single nACh receptor, in which firstly the stationary distribution of voltage is calculated based on our new method on solving the high-dimensional ODEs with variable coefficients...

Lithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory effects on postsynaptic receptors, the underlying mechanism by which lithium regulates synaptic transmission has not been fully elucidated. In this work, by using the advantageous neuromuscular synapse, we evaluated the effect of lithium on the stability of postsynaptic nicotinic acetylcholine receptors (nAChRs) in vivo. We found that in normally innervated neuromuscular synapses, lithium chloride significantly decreased the turnover of nAChRs by reducing their internalization...

Cholinergic neurotransmission is a key signal pathway in the peripheral nervous system and in several branches of the central nervous system. Despite the fact that it has been studied extensively for a long period of time, some aspects of its regulation still have not yet been established. One is the relationship between the nicotine-induced autoregulation of acetylcholine (ACh) release with changes in the concentration of presynaptic calcium levels. The mouse neuromuscular junction of m. Levator Auris Longus was chosen as the model of the cholinergic synapse...

The fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes are the predominant catabolic regulators of the major endocannabinoids (eCBs) anadamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively. The expression and roles of eCBs during early embryogenesis remain to be fully investigated. Here, we inhibited FAAH and MAGL in zebrafish embryos during the first 24 h of life and examined motor neuron and locomotor development at 2 and 5 days post fertilization (dpf). Application of the dual FAAH/MAGL inhibitor, JZL195 (2 µmol l-1), resulted in a reduction in primary and secondary motor neuron axonal branching...

Nicotinic acetylcholine receptors (nAChRs) are members of the "cys-loop" ligand-gated ion channel superfamily that play important roles in both the peripheral and central system. At the neuromuscular junction, the endplate current is induced by ACh binding and nAChR activation, and then, the current declines to a small steady state, even though ACh is still bound to the receptors. The kinetics of nAChRs with high affinity for ACh but no measurable ion conductance is called desensitization. This adopted desensitization of nAChR channel currents might be an important mechanism for protecting cells against uncontrolled excitation...