Endocytosis of Synaptic Vesicle in Motor Nerve Endings of FUS Transgenic Mice with a Model of Amyotrophic Lateral Sclerosis.

In experiments on the motor nerve endings of the diaphragm of transgenic FUS mice with a model of amyotrophic lateral sclerosis at the pre-symptomatic stage of the disease, the processes of transmitter release and endocytosis of synaptic vesicles were studied. In FUS mice, the intensity of transmitter release during high-frequency stimulation of the motor nerve (50 imp/sec) was lowered. At the same duration of stimulation, the loading of fluorescent dye FM1-43 was lower in FUS mice.

α-Adrenergic Receptor Blockade Inhibits Langendorff-Isolated Rat Heart Work.

We studied the effect of selective α-adrenergic receptor antagonist JP-1302 in concentrations of 10-10 M on inotropy, chronotropy, and coronary flow in the Langendorff-isolated rat heart. JP-1302 in all studied concentrations decreased the left-ventricular myocardium force contraction, HR, and coronary flow. The maximum inotropic, chronotropic, and vascular effects were observed when the antagonist was applied to the perfused solution in a concentration of 10 M.

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.

The Effect of α-Adrenoreceptors Blockade on the Isolated Rat Heart during the Formation of Sympathetic Innervation.

We studied the effects of the α-adrenergic receptor antagonist yohimbine (10-10 M) on inotropy, chronotropy, and coronary flow in the Langendorff-isolated heart from 3- and 6-week-old rats. Yohimbine affected all the studied functional parameters of the isolated heart. The force of contraction of the left ventricular myocardium, HR, and coronary flow decreased at all studied concentrations of the antagonist.

Effect of Clonidine Hydrochloride on Isolated Newborn Rat Heart.

The concentration dependenies of the chronotropic response and changes in blood supply to the isolated heart of 7-day-old newborn rats induced by application of α2-adrenergic receptor agonist clonidine hydrochloride in concentrations of 10-10 M were revealed. The minimum concentration of α2-adrenergic receptor agonist caused tachycardia, while higher concentrations led to bradycardia. The maximum effect manifesting in a decrease in coronary flow was recorded at the minimum concentration of the agonist, while the highest concentration had no effect on the coronary flow.

Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension.

Muscle disuse and denervation leads to muscle atrophy, but underlying mechanisms can be different. Previously, we have found ceramide (Cer) accumulation and lipid raft disruption after acute hindlimb suspension (HS), a model of muscle disuse. Herein, using biochemical and fluorescent approaches the influence of unilateral denervation itself and in combination with short-term HS on membrane-related parameters of rat soleus muscle was studied.

Intracellular Acidification Suppresses Synaptic Vesicle Mobilization in the Motor Nerve Terminals.

Intracellular protons play a special role in the regulation of presynaptic processes, since the functioning of synaptic vesicles and endosomes depends on their acidification by the H+-pump. Furthermore, transient acidification of the intraterminal space occurs during synaptic activity. Using microelectrode recording of postsynaptic responses (an indicator of neurotransmitter release) and exo-endocytic marker FM1-43, we studied the effects of intracellular acidification with propionate on the presynaptic events underlying neurotransmitter release.

Comparative Analysis of Cardiac Effects of α-Adrenoreceptor Stimulation In Vivo and Ex Vivo in Newborn Rats.

The study examined the effects of α-adrenoceptor stimulation on chronotropic function of Langendorff-perfused isolated heart ex vivo and on cardiac chronotropy in vivo in 7-day-old rats. α-Adrenergic receptor agonist A-61603 reduced heart chronotropy only in the whole organism. No chronotropic effects of selective stimulation of α-adrenergic receptors on isolated hearts were observed in ex vivo experiments.

Effect of Neuropeptide Y on Action Potential of Working Right Atrial Cardiomyocytes in Early Postnatal Ontogeny.

The effects of neuropeptide Y (10-10 M) on electrical activity of right atrial cardiomyocytes of rats aging 7, 21, and 100 days were examined in vitro. Neuropeptide Y affected the amplitude-temporal parameters of the action potential in these cells. It decreased the duration of repolarization phase in 7-day-old rats in concentrations of 10 and 10 M, in 21-day-old rats at 10 and 10 M, and in 100-day-old at 10 M.

Effect of Stimulation of α-Adrenergic Receptors on Action Potential of Working Cardiomyocytes in Rat Atrium.

The study examined the effect of clonidine hydrochloride (10-10 М) on electrical activity of working cardiomyocytes in rat right atrium. Stimulation of α-adrenergic receptor with clonidine changed electrical activity of the heart. All tested concentrations of the agonist lengthened the action potential and decreased the firing rate of cardiomyocytes in a dose-dependent manner.

Changes in Membrane Ceramide Pools in Rat Soleus Muscle in Response to Short-Term Disuse.

Lipid raft disruption is an early event during skeletal muscle unloading. Ceramide (Cer) serves as a signaling lipid that can contribute to lipid raft disturbance and muscle atrophy. Using biochemical and fluorescent approaches, the distribution of Cer and related molecules in the rat soleus muscle subjected to 12 h of hindlimb suspension (HS) was studied.

Effect of If Current Blockade on Newborn Rat Heart Isolated According to Langendorff.

The study examined the effects of hyperpolarization-activated funny current (If) on HR and coronary flow in Langendorff-isolated hearts from newborn rats. Blockade of If current with ZD7288 changed the examined cardiac parameters. The blocker in a concentration of 10 M decreased HR by 26.

Correction: Minimal model of interictal and ictal discharges "Epileptor-2".

[This corrects the article DOI: 10.1371/journal.pcbi.

Septin Polymerization Slows Synaptic Vesicle Recycling in Motor Nerve Endings.

Septins are GTP-binding proteins recognized as a component of the cytoskeleton. Despite the fact that septins are highly expressed by neurons and can interact with the proteins that participate in synaptic vesicle exocytosis and endocytosis, the role of septins in synaptic transmission and the synaptic vesicle recycling mechanisms is poorly understood. In this study, neurotransmitter release and synaptic vesicle exocytosis and endocytosis were investigated by microelectrode intracellular recording of end-plate potentials and fluorescent confocal microscopy in mouse diaphragm motor nerve endings during septin polymerization induced by forchlorfenuron application.

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.

Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer's Disease.

Background/objective: Alzheimer's disease (AD) is a progressive incurable neurodegenerative disorder. Glial cell line-derived neurotrophic factor (GDNF) is a prominent regulator of brain tissue and has an impressive potential for use in AD therapy. While its metabolism is still not fully understood, delivering neuropeptides such as GDNF via umbilical cord blood mononuclear cells (UCBMCs) to the sites of neurodegeneration is a promising approach in the development of innovative therapeutic avenues.

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).

Dysfunction of Neuromuscular Synapses in the Genetic Model of Alzheimer's Disease.

The function of synaptic transmission and presynaptic vesicular cycle in the neuromuscular synapses of the diaphragm was studied in transgenic APP/PS1 mice (Alzheimer's disease model). The decrease in the quantal content of end-plate potential, intense depression of the amplitude of terminal plate potentials under conditions of lasting high frequency stimulation (50 Hz), a drastic prolongation of the synaptic vesicle recycling time in APP/PS1 mice in comparison with wild type mice were detected. Manifest dysfunction of the neuromuscular synapses, caused by disordered neurosecretion and recycling of the synaptic vesicles in the presynaptic nerve endings, was detected in the Alzheimer's disease model on transgenic APP/PS1 mice.

Effect of α-Adrenoceptor Stimulation on Functional Parameters of Langendorff-Isolated Rat Heart.

We studied the effect of α-adrenoreceptor agonist clonidine hydrochloride in concentrations of 10-10 M on inotropy, chronotropy, and coronary flow in Langendorff-isolated heart of adult rats. It was found that α-adrenoreceptor agonist changed all studied parameters. Left ventricular myocardium contraction force decreased after application of all tested concentrations, the maximum effect was observed at a concentration of 10 M.

Effect of Neuropeptide Y on Action Potential Generation in Working Cardiomyocytes of the Right Atrium in Rat Heart.

We studied the effect of neuropeptide Y in concentrations of 10-10 M on electrical activity of adult rat right atrial cardiomyocytes with preserved spontaneous activity. Neuropeptide Y was found to modulate the amplitude-time parameters of action potential: in concentrations of 10 and 10 M it reduced the membrane potential, increased the amplitude of action potential and duration of the repolarization phase, and reduced the frequency of action potential generation. In concentration of 10 M, neuropeptide Y produced stronger effect on the analyzed parameters, while in concentration of 10 M it produced no significant changes.

Minimal model of interictal and ictal discharges "Epileptor-2".

Seizures occur in a recurrent manner with intermittent states of interictal and ictal discharges (IIDs and IDs). The transitions to and from IDs are determined by a set of processes, including synaptic interaction and ionic dynamics. Although mathematical models of separate types of epileptic discharges have been developed, modeling the transitions between states remains a challenge.

Clomipramine counteracts lipid raft disturbance due to short-term muscle disuse.

Disuse-induced skeletal muscle dysfunction is a serious consequence of long-term spaceflight, numerous diseases and conditions for which treatment possibilities are still strictly limited. We have previously shown that acute hindlimb suspension (HS)-mediated disuse disrupts membrane lipid rafts in the unloaded muscle. Here, we investigated whether pretreatment of rats with the inhibitor of acid sphingomyelinase, clomipramine (1.

Human Gene Expression Alters Active Zone Distribution and Spontaneous Neurotransmitter Release at the Larval Neuromuscular Junction.

This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of , the UAS-GAL4 system was used.

Cholesterol in the Pathogenesis of Alzheimer's, Parkinson's Diseases and Autism: Link to Synaptic Dysfunction.

In our previous review, we described brain cholesterol metabolism in control conditions and in the case of some rare neurological pathologies linked to defects in the genes which are directly involved in the synthesis and/or traffic of cholesterol. Here, we have analyzed disruptions in cholesterol homeostasis in widespread neurodegenerative diseases (Alzheimer's and Parkinson's diseases) and autism spectrum disorders. We particularly focused on the synaptic dysfunctions that could arise from changes in both membrane cholesterol availability and oxysterol production.