- Cognitive performance is associated with cerebral oxygenation and peripheral oxygen saturation, but not plasma catecholamines, during graded normobaric hypoxia. [Journal Article]
- EPExp Physiol 2019 Jun 13
- What is the central question of this study? What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and…
What is the central question of this study? What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and their importance? We found that 1) performance of a complex central executive task (n-back) was reduced FiO2 0.12; 2) there was a strong correlation between performance of the n-back task and reductions in SpO2 and cerebral oxygenation; and 3) plasma adrenaline, noradrenaline, cortisol, and copeptin were not correlated with cognitive performance.
- Blunted sympathoadrenal activation accompanies hemodynamic stability after early ventilation and delayed cord clamping at birth in preterm lambs. [Journal Article]
- PRPediatr Res 2019 Jun 10
- CONCLUSIONS: Hemodynamic stability at birth after DCC is accompanied by sub-threshold rises in circulating norepinephrine and epinephrine and thus blunted sympathoadrenal activation.
- Stress effects on the regulation of parturition in different domestic animal species. [Review]
- ARAnim Reprod Sci 2019 Apr 27
- This review summarizes current knowledge on stress-like responses in parturient animals and their role for the onset and fine-tuning of parturition. The antepartum maternal cortisol increase is part …
This review summarizes current knowledge on stress-like responses in parturient animals and their role for the onset and fine-tuning of parturition. The antepartum maternal cortisol increase is part of the endocrine changes that initiate parturition but a further increase in cortisol release during labor indicates a stress response. During the last minutes of delivery, sinus arrhythmias occur in 80% of foaling mares and 60% of calving cows. Expulsion of the neonate is thus characterized by parasympathetic dominance. In late-pregnant cows transported by road, cortisol concentrations increased but relations between transport stress and abortion remain unclear. In mares, transport not only elicited a stress response but also advanced the time of foaling. Transferring parturient rats, mice and pigs after birth of the first pup or piglet, respectively, to a stressful environment prolonged the time until delivery of the next littermate. In rats and pigs, this was caused by an increased opioidergic tone that restrained oxytocin release. In mice, a stress-induced delay of subsequent deliveries was caused by increased sympathoadrenal activity. When foaling mares were transferred to an uncomfortable stable at fetal membrane rupture, time until complete birth of the foal was doubled. As in mice, increased sympathetic activity was the mechanism delaying the progress of foaling. An increased sympathetic activity is also present in parturient cows disturbed during an early stage of calving. In equine and bovine neonates, the immediate postnatal period is characterised by high sympathetic activity and an increase in cortisol concentration, indicating a pronounced stress-like response.
- Wnt Signaling Is a Major Determinant of Neuroblastoma Cell Lineages. [Journal Article]
- FMFront Mol Neurosci 2019; 12:90
- The neural crest (NC), which has been referred to as the fourth germ layer, comprises a multipotent cell population which will specify diverse cells and tissues, including craniofacial cartilage and …
The neural crest (NC), which has been referred to as the fourth germ layer, comprises a multipotent cell population which will specify diverse cells and tissues, including craniofacial cartilage and bones, melanocytes, the adrenal medulla and the peripheral nervous system. These cell fates are known to be determined by gene regulatory networks (GRNs) acting at various stages of NC development, such as induction, specification, and migration. Although transcription factor hierarchies and some of their interplay with morphogenetic signaling pathways have been characterized, the full complexity of activities required for regulated development remains uncharted. Deregulation of these pathways may contribute to tumorigenesis, as in the case of neuroblastoma, a frequently lethal embryonic cancer thought to arise from the sympathoadrenal lineage of the NC. In this "Hypothesis and Theory" article, we utilize the next generation sequencing data from neuroblastoma cells and tumors to evaluate the possible influences of Wnt signaling on NC GRNs and on neuroblastoma cell lineages. We propose that Wnt signaling is a major determinant of regulatory networks that underlie mesenchymal/neural crest cell (NCC)-like cell identities through PRRX1 and YAP/TAZ transcription factors. Furthermore, Wnt may also co-operate with Hedgehog signaling in driving proneural differentiation programmes along the adrenergic (ADRN) lineage. Elucidation of Signaling Regulatory Networks can augment and complement GRNs in characterizing cell identities, which may in turn contribute to the design of improved therapeutics tailored to primary and relapsing neuroblastoma.
- β1-adrenergic receptors mediate plasma acyl-ghrelin elevation and depressive-like behavior induced by chronic psychosocial stress. [Journal Article]
- NNeuropsychopharmacology 2019; 44(7):1319-1327
- The ghrelin system is a key component of the mood and metabolic responses to chronic psychosocial stress. For example, circulating acyl-ghrelin rises in several rodent and human stress models, admini…
The ghrelin system is a key component of the mood and metabolic responses to chronic psychosocial stress. For example, circulating acyl-ghrelin rises in several rodent and human stress models, administered acyl-ghrelin induces antidepressant-like behavioral responses in mice, and mice with deleted ghrelin receptors (GHSRs) exhibit exaggerated depressive-like behaviors, changed eating behaviors, and altered metabolism in response to chronic stress. However, the mechanisms mediating stress-induced rises in ghrelin are unknown and ghrelin's antidepressant-like efficacy in the setting of chronic stress is incompletely characterized. Here, we used a pharmacological approach in combination with a 10-day chronic social defeat stress (CSDS) model in male mice to investigate whether the sympathoadrenal system is involved in the ghrelin response to stress. We also examined the antidepressant-like efficacy of administered ghrelin and the synthetic GHSR agonist GHRP-2 during and/or after CSDS. We found that administration of the β1-adrenergic receptor (β1AR) blocker atenolol during CSDS blunts the elevation of plasma acyl-ghrelin and exaggerates depressive-like behavior. Neither acute injection of acyl-ghrelin directly following CSDS nor its chronic administration during or after CSDS nor chronic delivery of GHRP-2 during and after CSDS improved stress-induced depressive-like behavior. Thus, β1ARs drive the acyl-ghrelin response to CSDS, but supplementing the natural increases in acyl-ghrelin with exogenous acyl-ghrelin or GHSR agonist does not further enhance the antidepressant-like actions of the endogenous ghrelin system in the setting of CSDS.
- External stress increases sympathoadrenal activity and prolongs the expulsive phase of foaling in pony mares. [Journal Article]
- TTheriogenology 2019 Apr 01; 128:110-115
- Mares usually give birth when they perceive their environment as safe and therefore disturbance at foaling may inhibit labor. In this study, foaling mares were transferred to an unfamiliar environmen…
Mares usually give birth when they perceive their environment as safe and therefore disturbance at foaling may inhibit labor. In this study, foaling mares were transferred to an unfamiliar environment at rupture of the allantochorion (stress, n = 6) or were left undisturbed (control, n = 5). The progress of foaling, heart rate, heart rate variability (HRV) and plasma catecholamine, oxytocin and cortisol concentration were determined. In stressed mares, time from rupture of the allantochorion to appearance of the fetal feet (5.3 ± 1.1 vs. 1.6 ± 0.4 min) and total length of fetal expulsion were longer than in controls (both p < 0.05). Heart rate decreased during the expulsive phase of foaling in control mares (p < 0.01) but increased transiently in stressed mares. Heart rate calculated as percentage of the baseline was higher in stressed than in control mares (p = 0.05). HRV variables SDRR (standard deviation of the beat-to-beat interval) and RMSSD (root mean square of successive beat-to-beat differences) increased during foal expulsion (SDRR p < 0.01 and RMSSD p < 0.05). The increase in HRV was delayed in stressed compared to control mares (SDRR and RMSSD time x group p < 0.05). Plasma epinephrine and norepinephrine concentrations calculated as area under the curve for the expulsive phase of foaling were higher in stressed than control mares (p < 0.05). Concentrations of oxytocin and cortisol were elevated during foal expulsion (both p < 0.001) but not different between groups. In conclusion, disturbance of mares during expulsion of the foal prolonged foaling. This effect is most likely mediated via increased sympathetic activity and not inhibition of oxytocin release.
- Schwann Cell Precursors Generate the Majority of Chromaffin Cells in Zuckerkandl Organ and Some Sympathetic Neurons in Paraganglia. [Journal Article]
- FMFront Mol Neurosci 2019; 12:6
- In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning…
In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning of midgestation and are the main cellular source of adrenalin and noradrenalin released into the blood stream. In mammals, two different chromaffin organs emerge at a close distance to each other, the adrenal gland and Zuckerkandl organ (ZO). These two structures are found in close proximity to the kidneys and dorsal aorta, in a region where paraganglioma, pheochromocytoma and neuroblastoma originate in the majority of clinical cases. Recent studies showed that the chromaffin cells comprising the adrenal medulla are largely derived from nerve-associated multipotent Schwann cell precursors (SCPs) arriving at the adrenal anlage with the preganglionic nerve fibers, whereas the migratory neural crest cells provide only minor contribution. However, the embryonic origin of the ZO, which differs from the adrenal medulla in a number of aspects, has not been studied in detail. The ZO is composed of chromaffin cells in direct contact with the dorsal aorta and the intraperitoneal cavity and disappears through an autophagy-mediated mechanism after birth. In contrast, the adrenal medulla remains throughout the entire life and furthermore, is covered by the adrenal cortex. Using a combination of lineage tracing strategies with nerve- and cell type-specific ablations, we reveal that the ZO is largely SCP-derived and forms in synchrony with progressively increasing innervation. Moreover, the ZO develops hand-in-hand with the adjacent sympathetic ganglia that coalesce around the dorsal aorta. Finally, we were able to provide evidence for a SCP-contribution to a small but significant proportion of sympathetic neurons of the posterior paraganglia. Thus, this cellular source complements the neural crest, which acts as a main source of sympathetic neurons. Our discovery of a nerve-dependent origin of chromaffin cells and some sympathoblasts may help to understand the origin of pheochromocytoma, paraganglioma and neuroblastoma, all of which are currently thought to be derived from the neural crest or committed sympathoadrenal precursors.
- Metabolomics Analyses of 14 Classical Neurotransmitters by GC-TOF with LC-MS Illustrates Secretion of 9 Cell-Cell Signaling Molecules from Sympathoadrenal Chromaffin Cells in the Presence of Lithium. [Journal Article]
- ACACS Chem Neurosci 2019 Mar 20; 10(3):1369-1379
- The classical small molecule neurotransmitters are essential for cell-cell signaling in the nervous system for regulation of behaviors and physiological functions. Metabolomics approaches are ideal f…
The classical small molecule neurotransmitters are essential for cell-cell signaling in the nervous system for regulation of behaviors and physiological functions. Metabolomics approaches are ideal for quantitative analyses of neurotransmitter profiles but have not yet been achieved for the repertoire of 14 classical neurotransmitters. Therefore, this study developed targeted metabolomics analyses by full scan gas chromatography/time-of-flight mass spectrometry (GC-TOF) and hydrophilic interaction chromatography-QTRAP mass spectrometry (HILIC-MS/MS) operated in positive ionization mode for identification and quantitation of 14 neurotransmitters consisting of acetylcholine, adenosine, anandamide, aspartate, dopamine, epinephrine, GABA, glutamate, glycine, histamine, melatonin, norepinephrine, serine, and serotonin. GC-TOF represents a new metabolomics method for neurotransmitter analyses. Sensitive measurements of 11 neurotransmitters were achieved by GC-TOF, and three neurotransmitters were analyzed by LC-MS/MS (acetylcholine, anandamide, and melatonin). The limits of detection (LOD) and limits of quantitation (LOQ) were assessed for linearity for GC-TOF and LC-MS/MS protocols. In neurotransmitter-containing dense core secretory vesicles of adrenal medulla, known as chromaffin granules (CG), metabolomics measured the concentrations of 9 neurotransmitters consisting of the catecholamines dopamine, norepinephrine, and epinephrine, combined with glutamate, serotonin, adenosine, aspartate, glycine, and serine. The CG neurotransmitters were constitutively secreted from sympathoadrenal chromaffin cells in culture. Nicotine- and KCl-stimulated release of the catecholamines and adenosine. Lithium, a drug used for the treatment of bipolar disorder, decreased the constitutive secretion of dopamine and norepinephrine and decreased nicotine-stimulated secretion of epinephrine. Lithium had no effect on other secreted neurotransmitters. Overall, the newly developed GC-TOF with LC-MS/MS metabolomics methods for analyses of 14 neurotransmitters will benefit investigations of neurotransmitter regulation in biological systems and in human disease conditions related to drug treatments.
- Salivary biomarkers to monitor stress due to aggression after weaning in piglets. [Journal Article]
- RVRes Vet Sci 2019; 123:178-183
- In this study, the changes of salivary stress biomarkers were contrasted with skin lesions during weaning in piglets. The stress biomarkers evaluated were cortisol (as the reflection of hypothalamic-…
In this study, the changes of salivary stress biomarkers were contrasted with skin lesions during weaning in piglets. The stress biomarkers evaluated were cortisol (as the reflection of hypothalamic-pituitary-adrenal (HPA) axis), chromogranin A (CgA) and alpha amylase (sAA) (both as the reflection of sympathoadrenal-medullary (SAM) axis). In addition, the accumulation of skin lesions were assessed as proxy measures of aggression. One hundred and two Danbred piglets (51 female and 51 male) from primiparous and multiparous sows were studied from birth to two days post-weaning. Saliva sampling and lesion scoring were performed one day pre-weaning (-1), and one (+1) and two days post-weaning (+2). Our results show that on +1, there was a significant (P < .0001) increase in salivary cortisol, CgA and skin lesions; whereas on +2, there was a significant increase (P < .0001) in salivary CgA and skin lesions. CgA was correlated with the skin lesion score (r = 0.4; P < .0001). sAA did not significantly change at any sampling time. It can be concluded that stress associated to weaning, is associated with changes in salivary CgA and cortisol stress biomarkers and an increase in skin lesions. However, CgA shows higher correlation with skin lesions which indicates that stress due to fighting activates the SAM stress pathway. Therefore, a combination of physiological biomarkers (CgA and cortisol) and proxy of aggression (skin lesions) is preferable than the use of a single biomarker or behavioural indicator when monitoring the social stress response associated to weaning in piglets.
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- Absence of gut microbial colonization attenuates the sympathoadrenal response to hypoglycemic stress in mice: implications for human neonates. [Journal Article]
- PRPediatr Res 2019; 85(4):574-581
- CONCLUSIONS: Lack of microbiome selectively impaired adrenal catecholamine responses to hypoglycemia. We speculate that absent/delayed acquisition of flora (e.g., after antibiotic exposure) may compromise sympathoadrenal stress responsivity. Conversely, controlled manipulation of the intestinal microflora may provide a novel therapeutic opportunity to improve survival and overall health in preterm neonates.