Selected Contribution: Neurochemical phenotypes of MRF neurons influencing diaphragm and rectus abdominis activity

2003 ◽  
Vol 94 (1) ◽  
pp. 391-398 ◽  
Author(s):  
I. Billig ◽  
J. P. Card ◽  
B. J. Yates
Keyword(s):  
Pseudorabies Virus ◽  
Respiratory Activity ◽  
Respiratory Muscles ◽  
Abdominal Muscle ◽  
Respiratory Neurons ◽  
Acid Decarboxylase ◽  
Medullary Reticular Formation ◽  
Transneuronal Transport ◽  
Motoneuron Activity

In prior studies that used transneuronal transport of isogenic recombinants of pseudorabies virus, we established that medial medullary reticular formation (MRF) neurons sent collateralized projections to both diaphragm and abdominal muscle motoneurons. Furthermore, inactivation of MRF neurons in cats and ferrets increased the excitability of diaphragm and abdominal motoneurons, suggesting that MRF neurons controlling respiratory activity are inhibitory. To test this hypothesis, the present study determined the neurochemical phenotypes of MRF premotor respiratory neurons in the ferret by using immunohistochemical procedures. Dual-labeling immunohistochemistry combining pseudorabies virus injections into respiratory muscles with the detection of glutamic acid decarboxylase-like immunoreactive and glutamate-like immunoreactive cells showed that both GABAergic and glutamatergic MRF neurons project to respiratory motoneurons, although the latter are more common. These data suggest that the role of the MRF in respiratory regulation is multifaceted, as this region provides both inhibitory and excitatory influences on motoneuron activity.

Transneuronal tracing of neural pathways influencing both diaphragm and genioglossal muscle activity in the ferret

2003 ◽  
Vol 95 (4) ◽  
pp. 1453-1459 ◽  
Author(s):  
T Shintani ◽  
A. R. Anker ◽  
I Billig ◽  
J. P. Card ◽  
B. J. Yates
Keyword(s):  
Pseudorabies Virus ◽  
Fluorescent Protein ◽  
Upper Airway ◽  
Abdominal Muscle ◽  
Neural Pathways ◽  
Related Activity ◽  
Medullary Reticular Formation ◽  
Transneuronal Transport ◽  
Contraction Regulation ◽  
Green Fluorescent

In prior experiments that employed the transneuronal transport of isogenic recombinants of pseudorabies virus (PRV), we demonstrated that neurons located ventrally in the medial medullary reticular formation (MRF) of the ferret provide collateralized projections to both diaphragm and abdominal muscle motoneurons as well as to multiple abdominal muscle motoneuron pools. The goal of the present study was to determine whether single MRF neurons also furnish inputs to diaphragm motoneurons and those innervating an airway muscle with inspiratory-related activity: the tongue protruder genioglossus. For this purpose, PRV recombinants expressing unique reporters (β-galactosidase or enhanced green fluorescent protein) were injected into either the diaphragm or the genioglossal muscle. The virus injections produced transneuronal infection of overlapping populations of MRF neurons. A small proportion of these neurons (<15%) was infected by both PRV recombinants, which indicated that they provide collateralized inputs to genioglossal and diaphragm motoneurons. These findings show that, whereas some MRF neurons simultaneously influence the activity of upper airway and respiratory pump muscles, other cells in this brain stem region independently contribute to diaphragm and genioglossal muscle contraction regulation.

Respiratory response to partial paralysis in anesthetized dogs

1984 ◽  
Vol 56 (6) ◽  
pp. 1583-1588 ◽  
Author(s):  
A. Oliven ◽  
E. C. Deal ◽  
S. G. Kelsen ◽  
N. S. Cherniack
Keyword(s):  
Motor Activity ◽  
Respiratory Muscle ◽  
Respiratory Muscles ◽  
Peak Activity ◽  
Inspiratory Time ◽  
Muscle Paralysis ◽  
Anesthetized Dogs ◽  
Spontaneously Breathing ◽  
Partial Paralysis

The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract P432: Higher Muscle-to-Abdominal Cavity Ratio is Associated with Lower Odds of Type II Diabetes in Older Women

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Britta Larsen ◽  
Matthew Allison ◽  
Eugene Kang ◽  
Sarah Saad ◽  
Gail A Laughlin ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Abdominal Cavity ◽  
Abdominal Muscle ◽  
Normal Weight ◽  
Area Ratio ◽  
Type Ii ◽  
Obese Women ◽  
Abdominal Adipose Tissue ◽  
Race Ethnicity

Background: Excess abdominal adipose tissue has been identified as an important factor in the development of type II diabetes. Lean muscle tissue also plays an important role in glucose regulation, yet research on the role of muscle in diabetes etiology is limited. Abdominal muscle mass could be particularly relevant for normal weight diabetics, for whom excessive abdominal adipose tissue may play less of a role. Objective: To explore the association between muscle-to-abdominal cavity area ratio and prevalent diabetes in older community-dwelling women in the Rancho Bernardo Study, UCSD Filipino Women’s Health Study, and the Health Assessment Study of African-American Women. Methods: Participants were 421 women (40% Caucasian, 28% Filipina, 32% African American) with a mean age of 64 (6.9) years. Abdominal muscle and fat areas were measured using computed tomography (CT) scans, and were used to compute a muscle-to-abdominal cavity area ratio (MACR). Based on body mass index (BMI), participants were classified as normal weight (18-24.9 kg/m2), overweight (25-29.9), or obese (30+). Prevalent diabetes was defined as self-report of physician diagnosis, anti-diabetes medication use, fasting morning glucose ≥ 126 mg/dL or 2 hour glucose ≥ 200mg/dL. MACR was modeled per standard deviation (SD) and logistic regression was used to examine the association with diabetes while adjusting for relevant covariates. Results: Prevalent diabetes was seen in 12.8% of the sample (54 of 421). In age and race/ethnicity adjusted models, each SD increase in MACR was associated with significant reduced odds of diabetes (OR = 0.62, CI: 0.43-0.89, p = 0.01), which remained significant after further adjustment for BMI category, smoking, physical activity, hypertension, anti-hypertensive drugs, and estrogen use (OR = 0.64, CI: 0.41-0.98, p = .041). The association was modestly attenuated after further adjusting for visceral fat area (OR = 0.70, CI: 0.44-1.10, p = 0.12). Normal weight women with diabetes had significantly less total muscle (p = 0.045) and smaller MACR’s (p = 0.001) than those without diabetes, while this was not seen for overweight or obese women with diabetes. Stratified by BMI category, MACR was significantly associated with lower odds of diabetes for normal weight women across all three models (fully adjusted OR = 0.37, CI: 0.15-0.90, p =.03), yet was not associated with diabetes in any models for women who were overweight or obese (all p > 0.50). Interactions of MACR with race/ethnicity were not significant. Conclusions: Muscle-to-abdominal cavity ratio is associated with reduced likelihood of type II diabetes in women. This association differs by BMI category, with muscle showing the greatest protection in normal weight women, and no effect in overweight or obese women. This highlights the potential role of low muscle mass as a risk factor for diabetes, particularly in women who may appear to be at low risk.

Stress-Induced Changes in Ubiquinone Concentration and Alternative Oxidase in Plant Mitochondria

2001 ◽  
Vol 21 (3) ◽  
pp. 369-379 ◽  
Author(s):  
Vasily N. Popov ◽  
Albert C. Purvis ◽  
Vladimir P. Skulachev ◽  
Anneke M. Wagner
Keyword(s):  
Alternative Oxidase ◽  
Respiratory Activity ◽  
Plant Mitochondria ◽  
High Oxygen ◽  
Plant Tissues ◽  
Respiration Rates ◽  
Bell Peppers ◽  
Respiration Of Mitochondria ◽  
Induced Changes

We have investigated the influence of stress conditions such as incubation at 4°C and incubation in hyperoxygen atmosphere, on plant tissues. The ubiquinone (Q) content and respiratory activity of purified mitochondria was studied. The rate of respiration of mitochondria isolated from cold-treated green bell peppers (Capsicum annuum L) exceeds that of controls, but this is not so for mitochondria isolated from cold-treated cauliflower (Brassica oleracea L). Treatment with high oxygen does not alter respiration rates of cauliflower mitochondria. Analysis of kinetic data relating oxygen uptake with Q reduction in mitochondria isolated from tissue incubated at 4°C (bell peppers and cauliflowers) and at high oxygen levels (cauliflowers) reveals an increase in the total amount of Q and in the percentage of inoxidizable QH2. The effects are not invariably accompanied by an induction of the alternative oxidase (AOX). In those mitochondria where the AOX is induced (cold-treated bell pepper and cauliflower treated with high oxygen) superoxide production is lower than in the control. The role of reduced Q accumulation and AOX induction in the defense against oxidative damage is discussed.

scholarly journals Functional Relevance of the Transmembrane Domain and Cytoplasmic Tail of the Pseudorabies Virus Glycoprotein H for Membrane Fusion

2018 ◽  
Vol 92 (12) ◽  
Author(s):  
Melina Vallbracht ◽  
Walter Fuchs ◽  
Barbara G. Klupp ◽  
Thomas C. Mettenleiter
Keyword(s):  
Membrane Fusion ◽  
Fusion Proteins ◽  
Essential Role ◽  
Pseudorabies Virus ◽  
Transmembrane Domain ◽  
Cytoplasmic Tail ◽  
Class Iii ◽  
Complex Needs ◽  
Hsv 1

ABSTRACTHerpesvirus membrane fusion depends on the core fusion machinery, comprised of glycoproteins B (gB) and gH/gL. Although gB structurally resembles autonomous class III fusion proteins, it strictly depends on gH/gL to drive membrane fusion. Whether the gH/gL complex needs to be membrane anchored to fulfill its function and which role the gH cytoplasmic (CD) and transmembrane domains (TMD) play in fusion is unclear. While the gH CD and TMD play an important role during infection, soluble gH/gL of herpes simplex virus 1 (HSV-1) seems to be sufficient to mediate cell-cell fusion in transient assays, arguing against an essential contribution of the CD and TMD. To shed more light on this apparent discrepancy, we investigated the role of the CD and TMD of the related alphaherpesvirus pseudorabies virus (PrV) gH. For this purpose, we expressed C-terminally truncated and soluble gH and replaced the TMD with a glycosylphosphatidylinositol (gpi) anchor. We also generated chimeras containing the TMD and/or CD of PrV gD or HSV-1 gH. Proteins were characterized in cell-based fusion assays and during virus infection. Although truncation of the CD resulted in decreased membrane fusion activity, the mutant proteins still supported replication of gH-negative PrV, indicating that the PrV gH CD is dispensable for viral replication. In contrast, PrV gH lacking the TMD, membrane-anchored via a lipid linker, or comprising the PrV gD TMD were nonfunctional, highlighting the essential role of the gH TMD for function. Interestingly, despite low sequence identity, the HSV-1 gH TMD could substitute for the PrV gH TMD, pointing to functional conservation.IMPORTANCEEnveloped viruses depend on membrane fusion for virus entry. While this process can be mediated by only one or two proteins, herpesviruses depend on the concerted action of at least three different glycoproteins. Although gB has features of bona fide fusion proteins, it depends on gH and its complex partner, gL, for fusion. Whether gH/gL prevents premature fusion or actively triggers gB-mediated fusion is unclear, and there are contradictory results on whether gH/gL function requires stable membrane anchorage or whether the ectodomains alone are sufficient. Our results show that in pseudorabies virus gH, the transmembrane anchor plays an essential role for gB-mediated fusion while the cytoplasmic tail is not strictly required.

scholarly journals Functional Role of N-Linked Glycosylation in Pseudorabies Virus Glycoprotein gH

2018 ◽  
Vol 92 (9) ◽  
pp. e00084-18 ◽  
Author(s):  
Melina Vallbracht ◽  
Sascha Rehwaldt ◽  
Barbara G. Klupp ◽  
Thomas C. Mettenleiter ◽  
Walter Fuchs
Keyword(s):  
Pseudorabies Virus ◽  
Viral Envelope ◽  
Fusion Activity ◽  
Virus Particles ◽  
Glycosylation Sites ◽  
Functional Relevance ◽  
And Function ◽  
Cell Spread

ABSTRACTMany viral envelope proteins are modified by asparagine (N)-linked glycosylation, which can influence their structure, physicochemical properties, intracellular transport, and function. Here, we systematically analyzed the functional relevance of N-linked glycans in the alphaherpesvirus pseudorabies virus (PrV) glycoprotein H (gH), which is an essential component of the conserved core herpesvirus fusion machinery. Upon gD-mediated receptor binding, the heterodimeric complex of gH and gL activates gB to mediate fusion of the viral envelope with the host cell membrane for viral entry. gH contains five potential N-linked glycosylation sites at positions 77, 162, 542, 604, and 627, which were inactivated by conservative mutations (asparagine to glutamine) singly or in combination. The mutated proteins were tested for correct expression and fusion activity. Additionally, the mutated gH genes were inserted into the PrV genome for analysis of function during virus infection. Our results demonstrate that all five sites are glycosylated. Inactivation of the PrV-specific N77 or the conserved N627 resulted in significantly reducedin vitrofusion activity, delayed penetration kinetics, and smaller virus plaques. Moreover, substitution of N627 greatly affected transport of gH in transfected cells, resulting in endoplasmic reticulum (ER) retention and reduced surface expression. In contrast, mutation of N604, which is conserved in theVaricellovirusgenus, resulted in enhancedin vitrofusion activity and viral cell-to-cell spread. These results demonstrate a role of the N-glycans in proper localization and function of PrV gH. However, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles.IMPORTANCEHerpesvirus infection requires fusion of the viral envelope with cellular membranes, which involves the conserved fusion machinery consisting of gB and the heterodimeric gH/gL complex. The bona fide fusion protein gB depends on the presence of the gH/gL complex for activation. Viral envelope glycoproteins, such as gH, usually contain N-glycans, which can have a strong impact on their folding, transport, and functions. Here, we systematically analyzed the functional relevance of all five predicted N-linked glycosylation sites in the alphaherpesvirus pseudorabies virus (PrV) gH. Despite the fact that mutation of specific sites affected gH transport,in vitrofusion activity, and cell-to-cell spread and resulted in delayed penetration kinetics, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles. Thus, our results demonstrate a modulatory but nonessential role of N-glycans for gH function.

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