Plasticity occurs in a specific phenotype of neurons in the nucleus tractus solitarius of dystrophin gene-mutated rats.

Duchenne muscular dystrophy (DMD) is a severe progressive neuromuscular disorder that causes cardiac and respiratory failure. Patients with DMD have tachycardia and autonomic nervous dysfunction at a young age, which can potentially worsen cardiorespiratory function. Therefore, we hypothesised that plasticity occurs in neurons of the cardiorespiratory brainstem nucleus (nucleus tractus solitarius [NTS]) due to DMD, thus affecting neuronal regulation because afferent information from cardiorespiratory organs changes with disease progression.

Ivabradine ameliorates cardiomyopathy progression in a Duchenne muscular dystrophy model rat.

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy caused by dystrophin mutations. Inevitable progressive cardiomyopathy is a current leading cause of premature death although respiratory management has improved the prognosis of patients with DMD. Recent evidence shows that reducing the heart rate is expected as one of the promising strategies for heart failure treatment, but administering a sufficient dose of β-blocker for patients with DMD with tachycardia is difficult because of their low blood pressure (BP).

Pretreatment with tadalafil attenuates cardiotoxicity induced by combretastatin A4 disodium phosphate in rats.

Combretastatin A4 disodium phosphate (CA4DP) is a prodrug of combretastatin A4 (CA4), a microtubule-disassembling agent that exhibits antitumor effects by inhibiting tumor cell proliferation and inducing morphological changes and apoptosis in vascular endothelial cells in tumors. However, cardiotoxicity induced by ischemia and hypertension is a severe adverse event. In this study, we focused on the fact that phosphodiesterase (PDE) 5 inhibitors dilate the heart and peripheral blood vessels and aimed to investigate whether co-administration of tadalafil, a PDE5 inhibitor, can attenuate cardiotoxicity without altering the antitumor effect of CA4DP.

Anti-tumor and cardiotoxic effects of microtubule polymerization inhibitors: The mechanisms and management strategies.

Microtubule polymerization inhibitors (MPIs) have long been used as anticancer agents because they inhibit mitosis. Microtubules are thought to play an important role in the migration of tumor cells and the formation of tumor blood vessels, and new MPIs are being developed. Many clinical trials of novel MPIs have been conducted in humans, while some clinical studies in dogs have also been reported.

Preliminary study of heart rate variability in Criollo horses for the elucidation of their neurophysiological characteristics of autonomic nerve function.

The Criollo is an Argentine horse breed with a calm temperament. Although its temperament is considered to be related to its neurophysiological characteristics, the details of this are unknown. Therefore, we analyzed the heart rate variability in Criollos as a preliminary study to deepen the neurophysiological understanding of their autonomic function.

Co-administration of JQ1, a bromodomain-containing protein 4 inhibitor, enhances the antitumor effect of combretastatin A4, a microtubule inhibitor, while attenuating its cardiotoxicity.

Combretastatin A4 (CA4) inhibits microtubule polymerization, and clinical trials of the prodrug, CA4 disodium phosphate (CA4DP), as an anti-cancer agent have been conducted. However, CA4DP has not been marketed to date because the margin between the effective dose and the cardiotoxic dose is insufficient. Meanwhile, bromodomain-containing protein 4 (BRD4) has been reported to be required for recovery from mitotic arrests induced by anti-microtubule drugs.

Favorable Effects of Virgin Coconut Oil on Neuronal Damage and Mortality after a Stroke Incidence in the Stroke-Prone Spontaneously Hypertensive Rat.

Stroke is consistently one of the top ten causes of morbidity and mortality globally, whose outcomes are quite variable, necessitating case-specific management. Prophylactic diets before the onset of stroke have been implicated to work. In this research, the effects of virgin coconut oil (VCO) on stroke were evaluated using a stroke-prone spontaneously hypertensive rat (SHRSP) model.

Chronic stimulation of group II metabotropic glutamate receptors in the medulla oblongata attenuates hypertension development in spontaneously hypertensive rats.

Baroreflex dysfunction is partly implicated in hypertension and one responsible region is the dorsal medulla oblongata including the nucleus tractus solitarius (NTS). NTS neurons receive and project glutamatergic inputs to subsequently regulate blood pressure, while G-protein-coupled metabotropic glutamate receptors (mGluRs) play a modulatory role for glutamatergic transmission in baroreflex pathways. Stimulating group II mGluR subtype 2 and 3 (mGluR2/3) in the brainstem can decrease blood pressure and sympathetic nervous activity.

Effects of environmental enrichment on autonomic nervous activity in NSY mice.

Environmental enrichment (EE) can reduce anxiety and stress in experimental animals, while little is known about the influence on autonomic nervous activity especially in disease animal models. Diabetes mellitus (DM) is associated with cardiovascular autonomic dysfunction, which can be characterized by a higher resting heart rate and a lower heart rate variability (HRV). We hypothesized that EE can enhance parasympathetic nervous activity while reducing disease progression in type 2 diabetic mice.

Early attenuation of autonomic nervous function in senescence accelerated mouse-prone 8 (SAMP8).

The senescence-accelerated mouse (SAM) strain has been established as an inbred strain with an accelerated aging phenotype. SAM prone-8 (SAMP8), one of the SAM strain, exhibits learning disability, immune deficiency, and circadian rhythm loss at a relatively young age. However, it has not been clarified whether aging affects the autonomic nervous activity in SAMP8.

Protection of signal processing at low temperature in baroreceptive neurons in the nucleus tractus solitarius of Syrian hamsters, a hibernating species.

We previously described synaptic currents between baroreceptor fibers and second-order neurons in the nucleus tractus solitarius (NTS) that were larger in Syrian hamsters than in rats. This suggested that although electrical activity throughout the hamster brain decreased as brain temperature declined, the greater synaptic input to its NTS would support continued operation of cardiorespiratory reflexes at low body temperatures. Here, we focused on properties that would protect these neurons against potential damage from the larger synaptic inputs, testing the hypotheses that hamster NTS neurons exhibit: 1) intrinsic N-methyl-D-aspartate receptor (NMDAR) properties that limit Ca(2+) influx to a greater degree than do rat NTS neurons and 2) properties that reduce gating signals to NMDARs to a greater degree than in rat NTS neurons.

Realignment of signal processing within a sensory brainstem nucleus as brain temperature declines in the Syrian hamster, a hibernating species.

Crucial for survival, the central nervous system must reliably process sensory information over all stages of a hibernation bout to ensure homeostatic regulation is maintained and well-matched to dramatically altered behavioral states. Comparing neural responses in the nucleus tractus solitarius of rats and euthermic Syrian hamsters, we tested the hypothesis that hamster neurons have adaptations sustaining signal processing while conserving energy. Using patch-clamp techniques, we classified second-order neurons in the nucleus as rapid-onset or delayed-onset spiking phenotypes based on their spiking onset to a depolarizing pulse (following a -80 mV prepulse).

Distinct tachykinin NK(1) receptor function in primate nucleus tractus solitarius neurons is dysregulated after second-hand tobacco smoke exposure.

Background And Purpose: Second-hand tobacco smoke (SHS) exposure in children increases the risk of asthma and sudden infant death syndrome. Epidemiological and experimental data have suggested SHS can alter neuroplasticity in the CNS, associated with substance P. We hypothesized that exposure to SHS in young primates changed the effect of substance P on the plasticity of neurons in the nucleus tractus solitarius (NTS), where airway sensory information is first processed in the CNS.

House-dust mite allergen and ozone exposure decreases histamine H3 receptors in the brainstem respiratory nuclei.

Allergic airway diseases in children are a common and a growing health problem. Changes in the central nervous system (CNS) have been implicated in contributing to some of the symptoms. We hypothesized that airway allergic diseases are associated with altered histamine H3 receptor expression in the nucleus tractus solitarius (NTS) and caudal spinal trigeminal nucleus, where lung/airway and nasal sensory afferents terminate, respectively.

Secondhand smoke exposure alters K+ channel function and intrinsic cell excitability in a subset of second-order airway neurons in the nucleus tractus solitarius of young guinea pigs.

Extended exposure to secondhand smoke (SHS) in infants and young children increases the incidence of cough, wheeze, airway hyper-reactivity and the prevalence and earlier onset of asthma. The adverse effects may result from environmentally-induced plasticity in the neural network regulating cough and airway function. Using whole-cell patch-clamp recordings in brainstem slices containing anatomically identified second-order lung afferent neurons in the nucleus tractus solitarius (NTS), we determined the effects of extended SHS exposure in young guinea pigs for a duration equivalent to human childhood on the intrinsic excitability of NTS neurons.

Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates.

Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated.

A novel postsynaptic group II metabotropic glutamate receptor role in modulating baroreceptor signal transmission.

The nucleus tractus solitarius (NTS) is essential for orchestrating baroreflex control of blood pressure. When a change in blood pressure occurs, the information is transmitted by baroreceptor afferent fibers to the central network by glutamate binding to ionotropic glutamate receptors on second-order baroreceptor neurons. Glutamate also activates presynaptic group II and III metabotropic glutamate receptors (mGluRs), depressing both glutamate and GABA release to modulate baroreceptor signal transmission.

Extended secondhand tobacco smoke exposure induces plasticity in nucleus tractus solitarius second-order lung afferent neurons in young guinea pigs.

Infants and young children experiencing extended exposure to secondhand smoke (SHS) have an increased occurrence of asthma, as well as increased cough, wheeze, mucus production and airway hyper-reactivity. Plasticity in lung reflex pathways has been implicated in causing these symptoms, as have changes in substance P-related mechanisms. Using whole-cell voltage-clamp recordings and immunohistochemistry in brainstem slices containing anatomically identified second-order lung afferent nucleus tractus solitarius (NTS) neurons, we determined whether extended SHS exposure during the equivalent period of human childhood modified evoked or spontaneous excitatory synaptic transmission, and whether those modifications were altered by endogenous substance P.

Air pollutants and cough.

Epidemiological studies have shown that exposure to air pollution is associated with respiratory symptoms and decreases in lung function. This paper reviews recent literature showing that exposure to particulate matter, irritant gases, environmental tobacco smoke (ETS), mixed pollutants, and molds is associated with an increase in cough and wheeze. Some pollutants, like particulate matter and mixed pollutants, appear to increase cough at least as much as wheeze.

Plasticity of brainstem mechanisms of cough.

The cough reflex is a brainstem reflex, consisting of specific sensory afferent nerves which trigger the reflex, by transmitting the sensory input over vagal or laryngeal nerves to a brainstem circuitry which processes and ultimately transforms the sensory input into a complex motor output to generate cough. The first synaptic target for the primary cough-related sensory input is the second-order neurons in the nucleus tractus solitarius (NTS). This position in the reflex pathway and intricate local circuits within the nucleus make it a strategic site where the sensory information can be modified.

Plasticity in the nucleus tractus solitarius and its influence on lung and airway reflexes.

The nucleus tractus solitarius (NTS) is the first central nervous system (CNS) site for synaptic contact of the primary afferent fibers from the lungs and airways. The signal processing at these synapses will determine the output of the sensory information from the lungs and airways to all downstream synapses in the reflex pathways. The second-order NTS neurons bring to bear their own intrinsic and synaptic properties to temporally and spatially integrate the sensory information with inputs from local networks, higher brain regions, and circulating mediators, to orchestrate a coherent reflex output.

Group I metabotropic glutamate receptors on second-order baroreceptor neurons are tonically activated and induce a Na+-Ca2+ exchange current.

The nucleus tractus solitarius (NTS) is essential for coordinating baroreflex control of blood pressure. The baroreceptor sensory fibers make glutamatergic synapses onto second-order NTS neurons. Glutamate spillover activates Group II and III presynaptic metabotropic glutamate receptors (mGluRs) on the baroreceptor central terminals to inhibit synaptic transmission, but the role of postsynaptic mGluRs is less understood.

Substance P presynaptically depresses the transmission of sensory input to bronchopulmonary neurons in the guinea pig nucleus tractus solitarii.

Substance P modulates the reflex regulation of respiratory function by its actions both peripherally and in the CNS, particularly in the nucleus tractus solitarii (NTS), the first central site for synaptic contact of the lung and airway afferent fibres. There is considerable evidence that the actions of substance P in the NTS augment respiratory reflex output, but the precise effects on synaptic transmission have not yet been determined. Therefore, we determined the effects of substance P on synaptic transmission at the first central synapses by using whole-cell voltage clamping in an NTS slice preparation.

A context-free data compression approach to measuring information transmission by action potentials.

Action potentials allow nervous systems to transmit information rapidly and efficiently over considerable distances, but what is the information they carry and how much can be carried by one neuron? Often, qualitative and vague descriptions are used, such as the firing rate representing intensity. Recent attempts to quantify information transmission by action potentials have concentrated on treating neurons as communication channels, whose information capacity can be estimated from their signal-to-noise ratios. However, this only indicates how much information could theoretically be carried, not the actual amount at any given time, and the ratio itself depends on assumptions about information coding.

Peripheral GABAergic inhibition of spider mechanosensory afferents.

Spider mechanosensory neurons receive an extensive network of efferent synapses onto their sensory dendrites, somata and distal axonal regions. The function of these synapses is unknown. Peripheral synapses are also found on crustacean stretch-receptor neurons but not on mechanosensory afferents of other species, although inhibitory GABAergic synapses are a common feature of centrally located axon terminals.