Immune-related oxysterol modulates neuromuscular transmission via non-genomic liver X receptor-dependent mechanism.

Inflammatory reactions induce changes in the neuromuscular system. The mechanisms underlying this link are unclear. Besides cytokines and reactive oxygen species (ROS), production of an antiviral oxysterol 25-hydroxycholesterol (25HC) by immune cells is quickly increased in response to inflammation.

Early differences in membrane properties at the neuromuscular junctions of ALS model mice: Effects of 25-hydroxycholesterol.

Aims: Plasma hyperlipidemia is a protective factor in amyotrophic lateral sclerosis (ALS) while cholesterol-lowering drugs aggravate the pathology. We hypothesize that this phenomenon can be linked with membrane lipid alterations in the neuromuscular junctions (NMJs) occurring before motor neuron loss.

Methods: Neurotransmitter release in parallel with lipid membrane properties in diaphragm NMJs of SOD1G93A (mSOD) mice at nine weeks of age (pre-onset stage) were assessed.

Cadmium desynchronizes neurotransmitter release in the neuromuscular junction: Key role of ROS.

Cd is one of the most widespread environmental pollutants and its accumulation in central and peripheral nervous systems leads to neurotoxicity as well as aggravation of common neurodegenerative diseases. Mechanism of the Cd toxicity is far from being resolved. Here, using microelectrode recordings of postsynaptic responses and fluorescent redox indicators we studied the effect of Cd in the submicromolar range on timing of neurotransmitter release and oxidative status in two functionally different compartments of the same frog motor nerve terminal.

Olesoxime, a cholesterol-like neuroprotectant restrains synaptic vesicle exocytosis in the mice motor nerve terminals: Possible role of VDACs.

Olesoxime is a cholesterol-like neuroprotective compound that targets to mitochondrial voltage dependent anion channels (VDACs). VDACs were also found in the plasma membrane and highly expressed in the presynaptic compartment. Here, we studied the effects of olesoxime and VDAC inhibitors on neurotransmission in the mouse neuromuscular junction.

Breakdown of phospholipids and the elevated nitric oxide are involved in M3 muscarinic regulation of acetylcholine secretion in the frog motor synapse.

Previously, we found that muscarine downregulates the acetylcholine release at the frog neuromuscular junction acting via M3 muscarinic receptors. Here, the molecular mechanisms underlying the inhibitory effect of muscarine on the quantal secretion of acetylcholine were studied. Inhibition of phospholipase C (with U-73122) prevented the reduction of evoked neurotransmitter release induced by muscarine.

Correction to: Abnormal Membrane Localization of α2 Isoform of Na,K-ATPase in m. soleus of Dysferlin-Deficient Mice.

The third author's name should read: V. V. Matchkov.

Abnormal Membrane Localization of α2 Isoform of Na,K-ATPase in m. soleus of Dysferlin-Deficient Mice.

Dysferlin protein plays a key role in the multimolecular complex responsible for the maintenance of sarcolemma integrity and skeletal muscle cell functioning. We studied the membrane distribution of nicotinic acetylcholine receptors and α2 isoform of Na,K-ATPase in motor endplates of m. soleus in dysferlin-deficient Bla/J mice (a dysferlinopathy model).

Oxysterol modulates neurotransmission via liver-X receptor/NO synthase-dependent pathway at the mouse neuromuscular junctions.

Elimination of brain cholesterol occurs in the form of 24S-hydroxycholesterol (24S-HCh) that may modulate physiological processes outside the brain. Here, using microelectrode recording of postsynaptic responses (end-plate potentials, EPPs) and fluorescent marker (FM1-43) for endo-exocytosis we studied the effects of prolonged application of 24S-HCh (2.5 h, 0.

Early endplate remodeling and skeletal muscle signaling events following rat hindlimb suspension.

Motor endplates naturally undergo continual morphological changes that are altered in response to changes in neuromuscular activity. This study examines the consequences of acute (6-12 hr) disuse following hindlimb suspension on rat soleus muscle endplate structural stability. We identify early changes in several key signaling events including markers of protein kinase activation, AMPK phosphorylation and autophagy markers which may play a role in endplate remodeling.

Targeted Nanoparticles for Selective Marking of Neuromuscular Junctions and ex Vivo Monitoring of Endogenous Acetylcholine Hydrolysis.

The present work for the first time introduces nanosensors for luminescent monitoring of acetylcholinesterase (AChE)-catalyzed hydrolysis of endogenous acetylcholine (ACh) released in neuromuscular junctions of isolated muscles. The sensing function results from the quenching of Tb(III)-centered luminescence due to proton-induced degradation of luminescent Tb(III) complexes doped into silica nanoparticles (SNs, 23 nm), when acetic acid is produced from the enzymatic hydrolysis of ACh. The targeting of the silica nanoparticles by α-bungarotoxin was used for selective staining of the synaptic space in the isolated muscles by the nanosensors.

24S-hydroxycholesterol suppresses neuromuscular transmission in SOD1(G93A) mice: A possible role of NO and lipid rafts.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the initial denervation of skeletal muscle and subsequent death of motor neurons. A dying-back pattern of ALS suggests a crucial role for neuromuscular junction dysfunction. In the present study, microelectrode recording of postsynaptic currents and optical detection of synaptic vesicle traffic (FM1-43 dye) and intracellular NO levels (DAF-FM DA) were used to examine the effect of the major brain-derived cholesterol metabolite 24S-hydroxycholesterol (24S-HC, 0.

Similar oxysterols may lead to opposite effects on synaptic transmission: Olesoxime versus 5α-cholestan-3-one at the frog neuromuscular junction.

Cholesterol oxidation products frequently have a high biological activity. In the present study, we have used microelectrode recording of end plate currents and FM-based optical detection of synaptic vesicle exo-endocytosis to investigate the effects of two structurally similar oxysterols, olesoxime (cholest-4-en-3-one, oxime) and 5ɑ-cholestan-3-one (5ɑCh3), on neurotransmission at the frog neuromuscular junction. Olesoxime is an exogenous, potentially neuroprotective, substance and 5ɑCh3 is an intermediate product in cholesterol metabolism, which is elevated in the case of cerebrotendinous xanthomatosis.

Inhibition of protein kinase C affects on mode of synaptic vesicle exocytosis due to cholesterol depletion.

Previous studies demonstrated that depletion of membrane cholesterol by 10mM methyl-beta-cyclodextrin (MCD) results in increased spontaneous exocytosis at both peripheral and central synapses. Here, we investigated the role of protein kinase C in the enhancement of spontaneous exocytosis at frog motor nerve terminals after cholesterol depletion using electrophysiological and optical methods. Inhibition of the protein kinase C by myristoylated peptide and chelerythrine chloride prevented MCD-induced increases in FM1-43 unloading, whereas the frequency of spontaneous postsynaptic events remained enhanced.