25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction.

Many synaptic vesicles undergo exocytosis in motor nerve terminals during neuromuscular communication. Endocytosis then recovers the synaptic vesicle pool and presynaptic membrane area. The kinetics of endocytosis may shape neuromuscular transmission, determining its long-term reliability.

Functional and Structural Changes in Diaphragm Neuromuscular Junctions in Early Aging.

Age-related impairment of the diaphragm causes respiratory complications. Neuromuscular junction (NMJ) dysfunction can be one of the triggering events in diaphragm weaknesses in old age. Prominent structural and functional alterations in diaphragm NMJs were described in elderly rodents, but NMJ changes in middle age remain unclear.

Protective properties of melanin from lichen Lobaria pulmonaria (L.) HOFFM. In models of oxidative stress in skeletal muscle.

Melanin is a dark pigment from the group of phenolic or indole polymers with inherent biocompatibility and antioxidant capacity. In extremophilic lichen Lobaria pulmonaria, melanin is responsible for protective properties against hostile environments. Herein, the ability of melanin extracted from L.

Mechanism of Purinergic Regulation of Neurotransmission in Mouse Neuromuscular Junction: The Role of Redox Signaling and Lipid Rafts.

Acetylcholine is the main neurotransmitter at the vertebrate neuromuscular junctions (NMJs). ACh exocytosis is precisely modulated by co-transmitter ATP and its metabolites. It is assumed that ATP/ADP effects on ACh release rely on activation of presynaptic G protein-coupled PY receptors.

25-hydroxycholesterol triggers antioxidant signaling in mouse atria.

Oxysterol, 25-hydroxycholesterol (25HC), is a potent regulator of immune reactions, its synthesis greatly increases by macrophages during inflammation. We hypothesize that 25HC can have cardioprotective effects by limiting consequences of excessive β-adrenoceptor (βAR) stimulation, particularly reactive oxygen species (ROS) production, in mouse atria. Isoproterenol, a βAR agonist, increased extra- and intracellular levels of ROS.

Targeted Liposomes Sensitize Plastic Melanoma to Ferroptosis via Senescence Induction and Coenzyme Depletion.

Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction.

β2-Adrenergic Regulation of the Neuromuscular Transmission and Its Lipid-Dependent Switch.

β2-Adrenoceptors (β2-ARs) are the most abundant subtype of adrenergic receptors in skeletal muscles. Their activation via a stabilization of postsynaptic architecture has beneficial effects in certain models of neuromuscular disorders. However, the ability of β2-ARs to regulate neuromuscular transmission at the presynaptic level is poorly understood.

The mechanism of 25-hydroxycholesterol-mediated suppression of atrial β1-adrenergic responses.

25-Hydroxycholesterol (25HC) is a biologically active oxysterol, whose production greatly increases during inflammation by macrophages and dendritic cells. The inflammatory reactions are frequently accompanied by changes in heart regulation, such as blunting of the cardiac β-adrenergic receptor (AR) signaling. Here, the mechanism of 25HC-dependent modulation of responses to β-AR activation was studied in the atria of mice.

Oxysterols in Central and Peripheral Synaptic Communication.

Cholesterol is a key molecule for synaptic transmission, and both central and peripheral synapses are cholesterol rich. During intense neuronal activity, a substantial portion of synaptic cholesterol can be oxidized by either enzymatic or non-enzymatic pathways to form oxysterols, which in turn modulate the activities of neurotransmitter receptors (e.g.

Effects of cholesterol oxidase on neurotransmission and acetylcholine levels at the mice neuromuscular junctions.

Membrane cholesterol oxidation is a hallmark of redox and metabolic imbalance, and it may accompany neurodegenerative disorders. Using microelectrode recordings of postsynaptic responses as well as fluorescent dyes for monitoring synaptic vesicle cycling and membrane properties, the action of enzymatic cholesterol oxidation on neuromuscular transmission was studied in the mice diaphragms. Cholesterol oxidase (ChO) at low concentration disturbed lipid-ordering specifically in the synaptic membranes, but it did not change markedly spontaneous exocytosis and evoked release in response to single stimuli.

The Mechanism of α2 adrenoreceptor-dependent Modulation of Neurotransmitter Release at the Neuromuscular Junctions.

α2-Adrenoreceptors (ARs) are main G-protein coupled autoreceptors in sympathetic nerve terminals and targets for dexmedetomidine (DEX), a widely used sedative. We hypothesize that α2-ARs are also potent regulators of neuromuscular transmission via G protein-gated inwardly rectifying potassium (GIRK) channels. Using extracellular microelectrode recording of postsynaptic potentials, we found DEX-induced inhibition of spontaneous and evoked neurotransmitter release as well as desynchronization of evoked exocytotic events in the mouse diaphragm neuromuscular junction.

Lipid-dependent regulation of neurotransmitter release from sympathetic nerve endings in mice atria.

Neurotransmitter release from sympathetic terminals is a key avenue for heart regulation. Herein, presynaptic exocytotic activity was monitored in mice atrial tissue using a false fluorescent neurotransmitter FFN511, a substrate for monoamine transporters. FFN511 labeling had similarity with tyrosine hydroxylase immunostaining.

Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice.

Amyotrophic lateral sclerosis (ALS) is manifested as skeletal muscle denervation, loss of motor neurons and finally severe respiratory failure. Mutations of RNA-binding protein FUS are one of the common genetic reasons of ALS accompanied by a 'dying back' type of degeneration. Using fluorescent approaches and microelectrode recordings, the early structural and functional alterations in diaphragm neuromuscular junctions (NMJs) were studied in mutant FUS mice at the pre-onset stage.

Sphingomyelinase modulates synaptic vesicle mobilization at the mice neuromuscular junctions.

Aims: Sphingomyelin is an abundant component of the presynaptic membrane and an organizer of lipid rafts. In several pathological conditions, sphingomyelin is hydrolyzed due to an upregulation and release of secretory sphingomyelinases (SMases). Herein, the effects of SMase on exocytotic neurotransmitter release were studied in the diaphragm neuromuscular junctions of mice.

K channels as ROS-dependent modulator of neurotransmitter release at the neuromuscular junctions.

Aims: Neurotransmitter release requires high energy demands, making the nerve terminals metabolically fragile and susceptible to oxidative stress. ATP-sensitive potassium (K) channels can be an important regulator orchestrating the influence of metabolic-related signals on exocytosis. Here, the relevance of ROS in K channel-dependent control of neurotransmitter release at the frog neuromuscular junction was studied.

Catecholamine-dependent hyperpolarization of the junctional membrane via β2- adrenoreceptor/G-protein/α2-Na-K-ATPase pathway.

We investigated the effects of catecholamines, adrenaline and noradrenaline, as well as β-adrenoceptor (AR) modulators on a resting membrane potential at the junctional and extrajunctional regions of mouse fast-twitch Levator auris longus muscle. The aim of the study was to find which AR subtypes, signaling molecules and Na,K-ATPase isoforms are involved in the hyperpolarizing action of catecholamines and whether this action could be accompanied by changes in the pump abundance on the sarcolemma. Adrenaline, noradrenaline and specific β2-AR agonist induced hyperpolarization of both junctional and extrajunctional membrane, but the underlying mechanisms were different.

Presynaptic Acetylcholine Receptors Modulate the Time Course of Action Potential-Evoked Acetylcholine Quanta Secretion at Neuromuscular Junctions.

For effective transmission of excitation in neuromuscular junctions, the postsynaptic response amplitude must exceed a critical level of depolarization to trigger action potential spreading along the muscle-fiber membrane. At the presynaptic level, the end-plate potential amplitude depends not only on the acetylcholine quanta number released from the nerve terminals in response to the nerve impulse but also on a degree of synchronicity of quanta releases. The time course of stimulus-phasic synchronous quanta secretion is modulated by many extra- and intracellular factors.

25-Hydroxycholesterol as a Signaling Molecule of the Nervous System.

Cholesterol is an essential component of plasma membrane and precursor of biological active compounds, including hydroxycholesterols (HCs). HCs regulate cellular homeostasis of cholesterol; they can pass across the membrane and vascular barriers and act distantly as para- and endocrine agents. A small amount of 25-hydroxycholesterol (25-HC) is produced in the endoplasmic reticulum of most cells, where it serves as a potent regulator of the synthesis, intracellular transport, and storage of cholesterol.

L-Tryptophan Aqueous Systems at Low Concentrations: Interconnection between Self-Organization, Fluorescent and Physicochemical Properties, and Action on Hydrobionts.

As shown by fluorescence monitoring of dissolved organic matter, amino acid -Trp can be present in natural water. The consequences of the presence of -Trp at low concentrations in surface water systems are not yet established for hydrobionts. Studying the physicochemical patterns, as well as their relationships to the bioeffects of -Trp solutions in the low concentration range, can provide new and important information regarding the unknown effects of -Trp.

GIRK channel as a versatile regulator of neurotransmitter release via L-type Ca channel-dependent mechanism in the neuromuscular junction.

G protein-gated inwardly rectifying potassium (GIRK) channels are one of the main regulators of neuronal excitability. Activation of GIRK channels in the CNS usually leads to postsynaptic inhibition. However, the function of GIRK channels in the presynaptic processes, notably neurotransmitter release form motor nerve terminals, is yet to be comprehensively understood.

Adrenergic receptors control frequency-dependent switching of the exocytosis mode between "full-collapse" and "kiss-and-run" in murine motor nerve terminal.

Aims: Neurotransmitter release from the synaptic vesicles can occur through two modes of exocytosis: "full-collapse" or "kiss-and-run". Here we investigated how increasing the nerve activity and pharmacological stimulation of adrenoceptors can influence the mode of exocytosis in the motor nerve terminal.

Methods: Recording of endplate potentials with intracellular microelectrodes was used to estimate acetylcholine release.

Frequency-Dependent Engagement of Synaptic Vesicle Pools in the Mice Motor Nerve Terminals.

Nerve terminals contain numerous synaptic vesicles (SVs) whose exo-endocytic cycling maintains neurotransmitter release. SVs may have different properties, thereby constituting separate pools. However, behavior of SV pools remains elusive in many synapses.

L-type Ca Channels at Low External Calcium Differentially Regulate Neurotransmitter Release in Proximal-Distal Compartments of the Frog Neuromuscular Junction.

L-type Ca channels (LTCCs) are key elements in electromechanical coupling in striated muscles and formation of neuromuscular junctions (NMJs). However, the significance of LTCCs in regulation of neurotransmitter release is still far from understanding. Here, we found that LTCCs can increase evoked neurotransmitter release (especially asynchronous component) and spontaneous exocytosis in two functionally different compartment of the frog NMJ, namely distal and proximal parts.