Age-Related Homeostatic Plasticity at Rodent Neuromuscular Junctions.

Motor ability decline remains a major threat to the quality of life of the elderly. Although the later stages of aging co-exist with degenerative pathologies, the long process of aging is more complicated than a simple and gradual degeneration. To combat senescence and the associated late-stage degeneration of the neuromuscular system, it is imperative to examine changes that occur during the long process of aging.

Resistance exercise in early-stage ALS patients, ALSFRS-R, Sickness Impact Profile ALS-19, and muscle transcriptome: a pilot study.

Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017).

Simulations of active zone structure and function at mammalian NMJs predict that loss of calcium channels alone is not sufficient to replicate LEMS effects.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disease thought to be caused by autoantibodies against P/Q-type voltage-gated calcium channels (VGCCs), which attack and reduce the number of VGCCs within transmitter release sites (active zones; AZs) at the neuromuscular junction (NMJ), resulting in neuromuscular weakness. However, patients with LEMS also have antibodies to other neuronal proteins, and about 15% of patients with LEMS are seronegative for antibodies against VGCCs. We hypothesized that a reduction in the number of P/Q-type VGCCs alone is not sufficient to explain LEMS effects on transmitter release.

Potentiation of neuromuscular transmission by a small molecule calcium channel gating modifier improves motor function in a severe spinal muscular atrophy mouse model.

Spinal muscular atrophy (SMA) is a monogenic disease that clinically manifests as severe muscle weakness owing to neurotransmission defects and motoneuron degeneration. Individuals affected by SMA experience neuromuscular weakness that impacts functional activities of daily living. We have used a mouse model of severe SMA (SMNΔ7) to test whether a calcium channel gating modifier (GV-58), alone or in combination with a potassium channel antagonist (3,4-diaminopyridine; 3,4-DAP), can improve neuromuscular function in this mouse model.

Neuromuscular Active Zone Structure and Function in Healthy and Lambert-Eaton Myasthenic Syndrome States.

The mouse neuromuscular junction (NMJ) has long been used as a model synapse for the study of neurotransmission in both healthy and disease states of the NMJ. Neurotransmission from these neuromuscular nerve terminals occurs at highly organized structures called active zones (AZs). Within AZs, the relationships between the voltage-gated calcium channels and docked synaptic vesicles govern the probability of acetylcholine release during single action potentials, and the short-term plasticity characteristics during short, high frequency trains of action potentials.

Oxaloacetate treatment preserves motor function in SOD1 mice and normalizes select neuroinflammation-related parameters in the spinal cord.

Amyotrophic lateral sclerosis (ALS) remains a devastating motor neuron disease with limited treatment options. Oxaloacetate treatment has a neuroprotective effect in rodent models of seizure and neurodegeneration. Therefore, we treated the ALS model superoxide dismutase 1 (SOD1) mice with oxaloacetate and evaluated their neuromuscular function and lifespan.

Impairment Mechanisms and Intervention Approaches for Aged Human Neuromuscular Junctions.

The neuromuscular junction (NMJ) is a chemical synapse formed between a presynaptic motor neuron and a postsynaptic muscle cell. NMJs in most vertebrate species share many essential features; however, some differences distinguish human NMJs from others. This review will describe the pre- and postsynaptic structures of human NMJs and compare them to NMJs of laboratory animals.

Super-resolution microscopy for analyzing neuromuscular junctions and synapses.

Super-resolution microscopy techniques offer subdiffraction limited resolution that is two- to ten-fold improved compared to that offered by conventional confocal microscopy. This breakthrough in resolution for light microscopy has contributed to new findings in neuroscience and synapse biology. This review will focus on the Structured Illumination Microscopy (SIM), Stimulated emission depletion (STED) microscopy, and Stochastic optical reconstruction microscopy (STORM) / Single molecule localization microscopy (SMLM) techniques and compare them for the better understanding of their differences and their suitability for the analysis of synapse biology.

Influence of Moringa oleifera extract, vitamin C, and sodium bicarbonate on heat stress-induced HSP70 expression and cellular immune response in rabbits.

The current study aimed to test the effect of Moringa oleifera extract (MOE), vitamin (Vit) C, and sodium bicarbonate (NaHCO) on heat stress (HS)-induced alterations in rabbits. Five groups of rabbits were designed as control, HS, HS + MOE, HS + Vit C, and HS + NaHCO. HS groups were exposed to high temperatures, while treatments were given in drinking water for 6 weeks.

Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V.

Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging.

Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones.

Impaired Mitophagy Plays a Role in Denervation of Neuromuscular Junctions in ALS Mice.

Motor neurons in amyotrophic lateral sclerosis (ALS) patients and animal models show degeneration from the nerve terminal, known as dying-back neuropathy. To investigate the mechanism underlying this neuropathy, we analyzed the neuromuscular junctions (NMJs) and motor neuron cell bodies in SOD1 mice using electron microscopy. NMJs of SOD1 mice exhibited significantly higher numbers of autophagosomes and degenerated mitochondria compared to wild-type controls.

Relative Contribution of Prolyl Hydroxylase-Dependent and -Independent Degradation of HIF-1alpha by Proteasomal Pathways in Cerebral Ischemia.

Hypoxia inducible factor-1 (HIF-1) is a key regulator in hypoxia and can determine the fate of brain cells during ischemia. However, the mechanism of HIF-1 regulation is still not fully understood in ischemic brains. We tested a hypothesis that both the 26S and the 20S proteasomal pathways were involved in HIF-1α degradation under ischemic conditions.

Dual-color STED microscopy reveals a sandwich structure of Bassoon and Piccolo in active zones of adult and aged mice.

Presynaptic active zones play a pivotal role as synaptic vesicle release sites for synaptic transmission, but the molecular architecture of active zones in mammalian neuromuscular junctions (NMJs) at sub-diffraction limited resolution remains unknown. Bassoon and Piccolo are active zone specific cytosolic proteins essential for active zone assembly in NMJs, ribbon synapses, and brain synapses. These proteins are thought to colocalize and share some functions at active zones.

Detergent-, solvent- and salt-compatible thermoactive alkaline serine protease from halotolerant alkaliphilic Bacillus sp. NPST-AK15: purification and characterization.

Alkaline protease produced by the halotolerant alkaliphilic Bacillus sp. strain NPST-AK15 was purified to homogeneity by the combination of ammonium sulfate precipitation, anion-exchange and gel permeation chromatography. The purified enzyme was a monomeric protein with an estimated molecular weight of 32 kDa.

Ischemic tolerance in an in vivo model of glutamate preconditioning.

Ischemia initiates a complicated biochemical cascade of events that triggers neuronal death. This study focuses on glutamate-mediated neuronal tolerance to ischemia-reperfusion. We employed an animal model of lifelong excess release of glutamate, the glutamate dehydrogenase 1 transgenic (Tg) mouse, as a model of in vivo glutamate preconditioning.

A novel cyclodextrin glycosyltransferase from Alkaliphilic Amphibacillus sp. NPST-10: purification and properties.

Screening for cyclodextrin glycosyltransferase (CGTase)-producing alkaliphilic bacteria from samples collected from hyper saline soda lakes (Wadi Natrun Valley, Egypt), resulted in isolation of potent CGTase producing alkaliphilic bacterium, termed NPST-10. 16S rDNA sequence analysis identified the isolate as Amphibacillus sp. CGTase was purified to homogeneity up to 22.

Hypoxia-inducible factor 1 protects hypoxic astrocytes against glutamate toxicity.

Stroke is a major neurological disorder characterized by an increase in the Glu (glutamate) concentration resulting in excitotoxicity and eventually cellular damage and death in the brain. HIF-1 (hypoxia-inducible factor-1), a transcription factor, plays an important protective role in promoting cellular adaptation to hypoxic conditions. It is known that HIF-1α, the regulatable subunit of HIF-1, is expressed by astrocytes under severe ischaemia.

Sociodemographic determinations of management behavior of diabetic patients attending a diabetic clinic in Alexandria. Part III: Relation between diabetics' sociodemographic background and health belief model variables.

The present work aims to study the relation between patient's health beliefs and psychological perception and demographic variables. The same subjects and methods applied in part I and II was adopted. It was found that a minority (1.