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1.
J Zhejiang Univ Sci B ; 25(5): 389-409, 2024 May 15.
Article in English, Chinese | MEDLINE | ID: mdl-38725339

ABSTRACT

The short neuropeptide F (sNPF) family of peptides is a multifunctional group of neurohormones involved in the regulation of various physiological processes in insects. They have been found in a broad spectrum of species, but the number of isoforms in the precursor molecule varies from one to four. The receptor for sNPF (sNPFR), which belongs to the G protein-coupled receptor family, has been characterized in various insect orders and was shown to be an ortholog of the mammalian prolactin-releasing peptide receptor (PrPR). The sNPF signaling pathway interacts with other neurohormones such as insulin-like peptides, SIFamide, and pigment-dispersing factors (PDFs) to regulate various processes. The main physiological function of sNPF seems to be involved in the regulation of feeding, but the observed effects are species-specific. sNPF is also connected with the regulation of foraging behavior and the olfactory system. The influence of sNPF on feeding and thus energy metabolism may also indirectly affect other vital processes, such as reproduction and development. In addition, these neurohormones are involved in the regulation of locomotor activity and circadian rhythm in insects. This review summarizes the current state of knowledge about the sNPF system in insects.


Subject(s)
Insecta , Neuropeptides , Signal Transduction , Animals , Neuropeptides/metabolism , Neuropeptides/physiology , Insecta/physiology , Insecta/metabolism , Circadian Rhythm/physiology , Feeding Behavior , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/physiology , Energy Metabolism
2.
J Neurophysiol ; 131(2): 137-151, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38150542

ABSTRACT

The Drosophila neuropeptide, DPKQDFMRFamide, was previously shown to enhance excitatory junctional potentials (EJPs) and muscle contraction by both presynaptic and postsynaptic actions. Since the peptide acts on both sides of the synaptic cleft, it has been difficult to examine postsynaptic modulatory mechanisms, particularly when contractions are elicited by nerve stimulation. Here, postsynaptic actions are examined in 3rd instar larvae by applying peptide and the excitatory neurotransmitter, l-glutamate, in the bathing solution to elicit contractions after silencing motor output by removing the central nervous system (CNS). DPKQDFMRFamide enhanced glutamate-evoked contractions at low concentrations (EC50 1.3 nM), consistent with its role as a neurohormone, and the combined effect of both substances was supra-additive. Glutamate-evoked contractions were also enhanced when transmitter release was blocked in temperature-sensitive (Shibire) mutants, confirming the peptide's postsynaptic action. The peptide increased membrane depolarization in muscle when co-applied with glutamate, and its effects were blocked by nifedipine, an L-type channel blocker, indicating effects at the plasma membrane involving calcium influx. DPKQDFMRFamide also enhanced contractions induced by caffeine in the absence of extracellular calcium, suggesting increased calcium release from the sarcoplasmic reticulum (SR) or effects downstream of calcium release from the SR. The peptide's effects do not appear to involve calcium/calmodulin-dependent protein kinase II (CaMKII), previously shown to mediate presynaptic effects. The approach used here might be useful for examining postsynaptic effects of neurohormones and cotransmitters in other systems.NEW & NOTEWORTHY Distinguishing presynaptic and postsynaptic effects of neurohormones is a long-standing challenge in many model organisms. Here, postsynaptic actions of DPKQDFMRFamide are demonstrated by assessing its ability to potentiate contractions elicited by direct application of the neurotransmitter, glutamate, when axons are silent and when transmitter release is blocked. The peptide acts at multiple sites to increase contraction, increasing glutamate-induced depolarization at the cell membrane, acting on L-type channels, and acting downstream of calcium release from the sarcoplasmic reticulum.


Subject(s)
Drosophila , Neuropeptides , Animals , Drosophila/metabolism , Neuromuscular Junction/physiology , Calcium , Neuropeptides/pharmacology , Muscle Contraction , Peptides/pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Glutamates , Neurotransmitter Agents/pharmacology
3.
Front Neurosci ; 17: 1228444, 2023.
Article in English | MEDLINE | ID: mdl-37746149

ABSTRACT

Parkinson's Disease (PD) is a prevalent and complex age-related neurodegenerative condition for which there are no disease-modifying treatments currently available. The pathophysiological process underlying PD remains incompletely understood but increasing evidence points to multiple system dysfunction. Interestingly, the past decade has produced evidence that exercise not only reduces signs and symptoms of PD but is also potentially neuroprotective. Characterizing the mechanistic pathways that are triggered by exercise and lead to positive outcomes will improve understanding of how to counter disease progression and symptomatology. In this review, we highlight how exercise regulates the neuroendocrine system, whose primary role is to respond to stress, maintain homeostasis and improve resilience to aging. We focus on a group of hormones - cortisol, melatonin, insulin, klotho, and vitamin D - that have been shown to associate with various non-motor symptoms of PD, such as mood, cognition, and sleep/circadian rhythm disorder. These hormones may represent important biomarkers to track in clinical trials evaluating effects of exercise in PD with the aim of providing evidence that patients can exert some behavioral-induced control over their disease.

4.
Peptides ; 163: 170975, 2023 05.
Article in English | MEDLINE | ID: mdl-36791916

ABSTRACT

Melanin-concentrating hormone (MCH) is a peptide related to the reproductive function by interacting with the hypothalamus-pituitary-gonadal axis. In addition to the MCH central production, it is also found in the blood with a putative role as a neurohormone. Thereby, our focus is on steroid hormones' role in regulating centrally produced MCH in the incerto-hypothalamic area (IHy) and the peripheral MCH in the serum. For this, we investigated the effect of estradiol and/or progesterone injection on the number of MCH immunoreactive (MCH-ir) neurons at the IHy and serum levels. For further study of the role of progesterone, we analyzed the effect of blockade of progesterone receptors by its antagonist on MCH-ir neurons at the IHy and serum. To identify whether such regulation over MCH is established before sexual maturation, we assessed the effect of peripubertal removal of steroid hormones on MCH-ir neurons at the IHy and serum levels at adult age. Our results show that injecting estradiol in ovariectomized female rats reduces the number of MCH-ir neurons in the IHy, in addition to its serum levels. Blockade of progesterone receptors in intact females increases the number of MCH-ir neurons in the IHy and its serum concentration. The regulation of these hormones over the MCH peptidergic system is established before sexual maturation, once the peripubertal removal of the ovaries changes the serum levels of MCH and the number of MCH-ir neurons in the IHy of adult females. Such results support the inhibitory role of steroid hormones over the MCH system.


Subject(s)
Hypothalamic Hormones , Progesterone , Female , Rats , Animals , Estradiol , Receptors, Progesterone , Pituitary Hormones , Hypothalamus/metabolism , Hypothalamic Hormones/metabolism , Melanins
5.
Cancers (Basel) ; 14(15)2022 Aug 04.
Article in English | MEDLINE | ID: mdl-35954455

ABSTRACT

High levels of ionizing radiation (IR) are known to induce neurogenesis defects with harmful consequences on brain morphogenesis and cognitive functions, but the effects of chronic low to moderate dose rates of IR remain largely unknown. In this study, we aim at defining the main molecular pathways impacted by IR and how these effects can translate to higher organizational levels such as behavior. Adult zebrafish were exposed to gamma radiation for 36 days at 0.05 mGy/h, 0.5 mGy/h and 5 mGy/h. RNA sequencing was performed on the telencephalon and completed by RNA in situ hybridization that confirmed the upregulation of oxytocin and cone rod homeobox in the parvocellular preoptic nucleus. A dose rate-dependent increase in differentially expressed genes (DEG) was observed with 27 DEG at 0.05 mGy/h, 200 DEG at 0.5 mGy/h and 530 DEG at 5 mGy/h. Genes involved in neurotransmission, neurohormones and hypothalamic-pituitary-interrenal axis functions were specifically affected, strongly suggesting their involvement in the stress response behavior observed after exposure to dose rates superior or equal to 0.5 mGy/h. At the individual scale, hypolocomotion, increased freezing and social stress were detected. Together, these data highlight the intricate interaction between neurohormones (and particularly oxytocin), neurotransmission and neurogenesis in response to chronic exposure to IR and the establishment of anxiety-like behavior.

6.
Front Physiol ; 13: 871045, 2022.
Article in English | MEDLINE | ID: mdl-36035477

ABSTRACT

Climate vulnerability and induced changes in physico-chemical properties of aquatic environment can bring impairment in metabolism, physiology and reproduction in teleost. Variation in environmental stimuli mainly acts on reproduction by interfering with steroidogenesis, gametogenesis and embryogenesis. The control on reproductive function in captivity is essential for the sustainability of aquaculture production. There are more than 3,000 teleost species across the globe having commercial importance; however, adequate quality and quantity of seed production have been the biggest bottleneck. Probiotics are widely used in aquaculture as a growth promoter, stress tolerance, pathogen inhibition, nutrient digestibility and metabolism, reproductive performance and gamete quality. As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, therefore it is considered to be a full-fledged endocrine organ. Researches on Gut-Brain-Gonad axis (GBG axis) and its importance on physiology and reproduction have already been highlighted for higher mammals; however, the study on fish physiology and reproduction is limited. While looking into the paucity of information, we have attempted to review the present status of microbiome and its interaction between the brain and gut. This review will address a process of the microbiome physiological mechanism involved in fish reproduction. The gut microbiota influences the BPG axis through a wide variety of compounds, including neuropeptides, neurotransmitter homologs and transmitters. Currently, research is being conducted to determine the precise process by which gut microbial composition influences brain function in fish. The gut-brain bidirectional interaction can influence brain biochemistry such as GABA, serotonin and tryptophan metabolites which play significant roles in CNS regulation. This review summarizes the fact, how microbes from gut, skin and other parts of the body influence fish reproduction through the Gut-Brain-Gonad axis.

7.
J Insect Physiol ; 142: 104429, 2022 10.
Article in English | MEDLINE | ID: mdl-35964679

ABSTRACT

Eclosion hormone (EH) is a neurohormone that plays a key role in the regulation of insect pre-ecdysis behavior at the end of each molt. Previous research has reported more than one EH gene was found in certain insects, with their functions and mechanisms still unclear. Here, aside from the classical EH gene orthologous group, we characterized another novel orthologous cluster of eclosion hormone-like (EHL) genes in Arthropoda and investigated the roles of EHL during development in Tribolium castaneum. T. castaneum EHL (TcEHL) shows high expression levels during pupal - adult development, which also positively responded to 20-hydroxyecdysone (20E) treatment as well as RNA interference (RNAi) of ECR (20E nuclear receptor). Knockdown of TcEHL prevented the tanning of the adult cuticle and caused lethal phenotypes. Further analysis indicated that knockdown of TcEHL could upregulate expression levels of the classical TcEH, and downregulate the ecdysis behavior cascade genes, as well as tanning pathway enzymes. This suggests a critical role for TcEHL in adult eclosion and cuticle tanning. In addition, our data indicated that TcEHL is responsible for the female reproduction process. Taken together, these results suggest that TcEHL has specific roles in adult cuticle tanning during the post-eclosion process and female reproduction. They also suggest that EHL gene is the ancestral copy for the EH family and it is functionally shuffled by synfunctionalization.


Subject(s)
Coleoptera , Insect Hormones , Tribolium , Animals , Coleoptera/genetics , Coleoptera/metabolism , Ecdysterone/metabolism , Female , Insect Hormones/metabolism , RNA Interference
8.
Biol Aujourdhui ; 216(3-4): 113-123, 2022.
Article in French | MEDLINE | ID: mdl-36744977

ABSTRACT

Oxytocin is a pleiotropic molecule which, in addition to its facilitating action during parturition and milk ejection, is involved in social and prosocial behaviors such as attachment. This article presents, after a brief historical review, the action of oxytocin during the milk ejection reflex. Oxytocin is indeed essential for this vital function in mammals. It is both a neurohormone released into the bloodstream by the axon terminals of the posterior pituitary and a neuromodulator released in the hypothalamus by the soma and dendrites of oxytocinergic magnocellular neurons. In addition, oxytocin is also released by the axon terminals of parvocellular neurons and axon collaterals of magnocellular neurons in the brain. Both maternal attachment in rats and ewes and attachment between sexual partners in the prairie vole, one of the few monogamous rodent species, are mediated by central oxytocin. However, neither administering oxytocin into the brain nor increasing expression of the oxytocin receptor in the nucleus accumbens using a gene transfer technique converts polygamous voles to monogamous ones. Unfortunately, translation of animal data to human remains problematic due to still unsolved difficulties in modifying the level of oxytocin in the brain.


Title: Comment, au fil du temps, l'ocytocine est devenue l'hormone de l'attachement. Abstract: L'ocytocine est une molécule pléiotrope qui, en plus de son action facilitatrice au cours de l'accouchement et de l'allaitement, est impliquée dans des comportements sociaux et prosociaux comme l'attachement. Cet article présente, après un bref rappel historique, l'action de l'ocytocine pendant le réflexe d'éjection de lait. L'ocytocine est en effet indispensable à cette fonction vitale chez les mammifères. Elle est à la fois une neurohormone, libérée dans la circulation sanguine par les terminaisons axonales de la post-hypophyse, et un neuromodulateur, libéré dans l'hypothalamus par le soma et les dendrites des neurones magnocellulaires ocytocinergiques. D'autre part, l'ocytocine est également libérée dans le cerveau par les terminaisons axonales des neurones parvocellulaires et des collatérales d'axones des neurones magnocellulaires. La libération centrale de l'ocytocine est à l'origine de ses effets dans l'attachement, qu'il s'agisse de l'attachement maternel comme chez la ratte et la brebis ou de l'attachement entre les partenaires sexuels chez le campagnol des prairies, une des rares espèces de rongeurs monogames. Toutefois, ni l'injection d'ocytocine dans le cerveau, ni l'augmentation de l'expression du récepteur de l'ocytocine dans le noyau accumbens grâce à une technique de transfert de gène, ne rendent monogames des campagnols polygames. La transposition à l'espèce humaine des données obtenues chez l'animal reste problématique en raison principalement de la difficulté à modifier le taux d'ocytocine dans le cerveau.


Subject(s)
Oxytocin , Receptors, Oxytocin , Animals , Female , Humans , Rats , Brain/metabolism , Neurons , Oxytocin/metabolism , Receptors, Oxytocin/metabolism , Sheep
9.
Front Endocrinol (Lausanne) ; 12: 760538, 2021.
Article in English | MEDLINE | ID: mdl-34867802

ABSTRACT

In this study, a novel Crustacean Hyperglycemic Hormone-type II gene (CHH-type II) was identified and biologically characterized in a shrimp, Penaeus monodon. Based on its structure and function, this gene was named P. monodon vitellogenesis-inhibiting hormone (PemVIH). The complete cDNA sequence of PemVIH consisted of 1,022 nt with an open reading frame (ORF) of 339 nt encoding a polypeptide of 112 amino acids. It was classified as a member of the CHH-type II family based on conserved cysteine residues, a characteristically positioned glycine residue, and the absence of CHH precursor-related peptide (CPRP) domain. The deduced mature PemVIH shared the highest sequence similarities with giant river prawn sinus gland peptide A. Unlike P. monodon gonad-inhibiting hormone (PemGIH), PemVIH was expressed only in the brain and ventral nerve cord, but not the eyestalks. Whole mount immunofluorescence using a newly generated PemVIH antiserum detected positive signals in neuronal cluster 9/11 and 17 of the brain, commissural ganglion (CoG), and neuronal clusters of ventral nerve cord. The presence of PemVIH-positive neurons in CoG, a part of stomatogastric nervous system, suggested a potential mechanism for crosstalk between nutritional and reproductive signaling. The role of PemVIH in vitellogenesis was evaluated using RNA interference technique. Temporal knockdown of PemVIH in female subadults resulted in a 3-fold increase in ovarian vitellogenin expression, suggesting an inhibitory role of PemVIH in vitellogenesis. This study provided novel insight into the control of vitellogenesis and additional strategies for improving ovarian maturation in P. monodon without the current harmful practice of eyestalk ablation.


Subject(s)
Invertebrate Hormones/metabolism , Ovary/metabolism , Penaeidae/metabolism , Vitellogenesis/physiology , Amino Acid Sequence , Animals , Arthropod Proteins/metabolism , Cloning, Molecular/methods , Female , Nerve Tissue Proteins/metabolism , Vitellogenins/metabolism
10.
J Psychiatr Res ; 137: 401-408, 2021 05.
Article in English | MEDLINE | ID: mdl-33765452

ABSTRACT

Psychiatric disorders are severe, debilitating conditions with unknown etiology and are commonly misdiagnosed, when based solely on clinical interviews, because of overlapping symptoms and similar familial patterns. Until now, no valid and objective biomarkers have been used to diagnose and differentiate between psychiatric disorders. We compared clinically tested serum indicators in terms of inflammation (C-reactive protein, complement proteins C3 and C4, and serum Immunoglobulins A, M, and G), nutrients (homocysteine, folate, and vitamin B12), and neurohormones (adrenocorticotropic hormone and cortisol) in patients with schizophrenia (SCZ, n = 1659), bipolar disorder (BD, n = 1901), and major depressive disorder (MDD, n = 1521) to investigate potential biomarkers. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these analytes. We found that compared with MDD, serum levels of C-reactive protein, C3, C4, and homocysteine were higher in SCZ and BD groups, and folate and vitamin B12 were lower in SCZ and BD groups. In contrast with BD, adrenocorticotropic hormone and cortisol increased in patients with MDD. Although ROC analysis suggested that they were not able to effectively distinguish between the three, these biological indicators showed different patterns in the three disorders. As such, more specific biomarkers should be explored in the future.


Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Schizophrenia , Humans , Nutrients , ROC Curve
11.
J Vet Intern Med ; 35(3): 1245-1254, 2021 May.
Article in English | MEDLINE | ID: mdl-33713485

ABSTRACT

BACKGROUND: Diuretic braking during furosemide continuous rate infusion (FCRI) curtails urine production. HYPOTHESIS: Renin-angiotensin-aldosterone system (RAAS) activation mediates braking, and RAAS inhibition will increase urine production. ANIMALS: Ten healthy purpose-bred male dogs. METHODS: Dogs received placebo, benazepril, or benazepril and spironolactone PO for 3 days before a 5-hour FCRI (0.66 mg/kg/h) in a 3-way, randomized, blinded, cross-over design. Body weight (BW), serum creatinine concentration (sCr), serum electrolyte concentrations, PCV, and total protein concentration were measured before PO medications, at hours 0 and 5 of FCRI, and at hour 24. During the FCRI, water intake, urine output, urine creatinine concentration, and urine electrolyte concentrations were measured hourly. Selected RAAS components were measured before and after FCRI. Variables were compared among time points and treatments. RESULTS: Diuretic braking and urine production were not different among treatments. Loss of BW, hemoconcentration, and decreased serum chloride concentration occurred during FCRI with incomplete recovery at hour 24 for all treatments. Although unchanged during FCRI, sCr increased and serum sodium concentration decreased at hour 24 for all treatments. Plasma aldosterone and angiotensin-II concentrations increased significantly at hour 5 for all treatments, despite suppressed angiotensin-converting enzyme activity during benazepril background treatment. CONCLUSIONS: The neurohormonal profile during FCRI supports RAAS mediation of diuretic braking in this model. Background treatment with benazepril with or without spironolactone did not mitigate braking, but was well tolerated. Delayed changes in sCr and serum sodium concentration and incomplete recovery of hydration indicators caused by furosemide hold implications for clinical patients.


Subject(s)
Furosemide , Renin-Angiotensin System , Aldosterone , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Benzazepines , Diuresis , Diuretics/pharmacology , Dogs , Furosemide/pharmacology , Male , Spironolactone/pharmacology
12.
Int J Mol Sci ; 22(4)2021 Feb 03.
Article in English | MEDLINE | ID: mdl-33546414

ABSTRACT

Leucokinins (LKs) constitute a neuropeptide family first discovered in a cockroach and later identified in numerous insects and several other invertebrates. The LK receptors are only distantly related to other known receptors. Among insects, there are many examples of species where genes encoding LKs and their receptors are absent. Furthermore, genomics has revealed that LK signaling is lacking in several of the invertebrate phyla and in vertebrates. In insects, the number and complexity of LK-expressing neurons vary, from the simple pattern in the Drosophila larva where the entire CNS has 20 neurons of 3 main types, to cockroaches with about 250 neurons of many different types. Common to all studied insects is the presence or 1-3 pairs of LK-expressing neurosecretory cells in each abdominal neuromere of the ventral nerve cord, that, at least in some insects, regulate secretion in Malpighian tubules. This review summarizes the diverse functional roles of LK signaling in insects, as well as other arthropods and mollusks. These functions include regulation of ion and water homeostasis, feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. Other functions are implied by the neuronal distribution of LK, but remain to be investigated.


Subject(s)
Hormones/genetics , Hormones/metabolism , Insecta , Invertebrates , Neuropeptides/genetics , Neuropeptides/metabolism , Animals , Gene Expression Regulation , Hormones/chemistry , Insect Control , Neurons/metabolism , Neuropeptides/chemistry , Organ Specificity/genetics , Pest Control , Phylogeny , Protein Binding , Receptors, Neuropeptide/metabolism , Signal Transduction , Species Specificity
13.
J Insect Physiol ; 129: 104193, 2021.
Article in English | MEDLINE | ID: mdl-33460707

ABSTRACT

The salivary gland of hematophagous arthropods is critical for blood meal acquisition, blood vessel localization, and secretion of digestive enzymes. Thus, there is significant interest in the regulation of salivary gland function and mechanisms driving the secretion of saliva and digestive proteins. We aimed to gain a broader understanding of the regulatory role of aminergic, cholinergic, and octopaminergic neuromodulators to saliva and protein secretion from the female A. aegypti salivary gland. Quantification of saliva after injection with neuromodulators showed that dopamine, serotonin, and pilocarpine increased the secretory activity of the salivary gland with potency rankings dopamine = serotonin > pilocarpine. No change in saliva secretion was observed with octopamine or ergonovine, which indicates the A. aegypti salivary gland may be regulated by dopaminergic, serotonergic, and cholinergic systems, but are not likely regulated by octopaminergic or tryptaminergic systems. Next, we studied the regulatory control of dopamine-mediated salivation. Data indicate extracellular calcium flux, but not neural function, is critical for dopamine-mediated salivation, which suggests epithelial transport of ions and not neuronal control is responsible for dopamine-mediated salivation. For regulation of protein secretion, data indicate dopamine or serotonin exposure facilitates amylase secretion, whereas serotonin but not dopamine exposure increased apyrase concentrations in the secreted saliva. General immunoreactivity to anti-rat D1-dopamine receptor antibody was observed, yet immunoreactivity to the anti-rat D2-receptor antibody was identified in the proximal regions of the lateral lobes and slight immunoreactivity in the distal portion of the lateral lobe, with no expression in the medial lobe.


Subject(s)
Aedes/physiology , Neurotransmitter Agents/pharmacology , Saliva , Salivary Glands , Amylases/drug effects , Amylases/metabolism , Animals , Apyrase/drug effects , Apyrase/metabolism , Dopamine/pharmacology , Female , Humans , Insect Proteins/drug effects , Pilocarpine/pharmacology , Rats , Receptors, Dopamine D1 , Saliva/chemistry , Saliva/drug effects , Salivary Glands/drug effects , Salivary Glands/physiology , Serotonin/pharmacology
14.
Card Fail Rev ; 6: e19, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32714567

ABSTRACT

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

15.
Front Physiol ; 11: 375, 2020.
Article in English | MEDLINE | ID: mdl-32477156

ABSTRACT

Background: We previously reported that bilateral sympathetic stellate ganglionectomy attenuated cardiac remodeling and fibrosis in rats with chronic volume overload. Transforming growth factor beta 1 (TGF-ß1) is a polypeptide member of the transforming growth factor beta superfamily of cytokines and actively involved in many pathological processes of cardiovascular diseases. The present study explored the impact of bilateral sympathetic stellate ganglionectomy on the TGF-ß1 pathway in this model. Methods and Results: Male Sprague-Dawley rats were randomly divided into sham (S) group, abdominal aorta-cava fistula (AV) group, and bilateral sympathetic stellate ganglionectomy after abdominal aorta-cava fistula (AD) group. Twelve weeks after the abdominal aorta-cava fistula surgery, the myocardial expressions of norepinephrine (NE) and hydroxyproline were significantly higher, while acetylcholine was downregulated in the AV group compared to the S group; the above changes were partly reversed in the AD group. The myocardial expression of TGF-ß1 and activity of Smad2/3 phosphorylation were also upregulated in the AV group compared to the S group, which could be reversed by bilateral sympathetic stellate ganglionectomy. In vitro, the TGF-ß1 expression in cultured myocardial fibroblasts and the proliferation of myocardial fibroblasts were significantly increased post-stimulation with NE in a dose-dependent manner, and these effects could be blunted by co-treatment with a TGF-ß1 inhibitor. Conclusion: Our study results indicate that stellate ganglionectomy decreases cardiac norepinephrine release, which leads to decreased TGF-ß1 release and reduced fibrosis in rats with chronic volume overload.

16.
Front Cardiovasc Med ; 7: 76, 2020.
Article in English | MEDLINE | ID: mdl-32478097

ABSTRACT

Vasovagal syncope (VVS) is the most common cause of syncope across all age groups. Nonetheless, despite its clinical importance and considerable research effort over many years, the pathophysiology of VVS remains incompletely understood. In this regard, numerous studies have been undertaken in an attempt to improve insight into the evolution of VVS episodes and many of these studies have examined neurohormonal changes that occur during the progression of VVS events primarily using the head-up tilt table testing model. In this regard, the most consistent finding is a marked increase in epinephrine (Epi) spillover into the circulation beginning at an early stage as VVS evolves. Reported alterations of circulating norepinephrine (NE), on the other hand, have been more variable. Plasma concentrations of other vasoactive agents have been reported to exhibit more variable changes during a VVS event, and for the most part change somewhat later, but in some instances the changes are quite marked. The neurohormones that have drawn the most attention include arginine vasopressin [AVP], adrenomedullin, to a lesser extent brain and atrial natriuretic peptides (BNP, ANP), opioids, endothelin-1 (ET-1) and serotonin. However, whether some or all of these diverse agents contribute directly to VVS pathophysiology or are principally a compensatory response to an evolving hemodynamic crisis is as yet uncertain. The goal of this communication is to summarize key reported neurohumoral findings in VVS, and endeavor to ascertain how they may contribute to observed hemodynamic alterations during VVS.

17.
J Insect Physiol ; 122: 104039, 2020 04.
Article in English | MEDLINE | ID: mdl-32113954

ABSTRACT

Predators can induce extreme stress and profound physiological responses in prey. Insects are the most dominant animal group on Earth and serve as prey for many different predators. Although insects have an extraordinary diversity of anti-predator behavioral and physiological responses, predator-induced stress has not been studied extensively in insects, especially at the molecular level. Here, we review the existing literature on physiological predator-induced stress responses in insects and compare what is known about insect stress to vertebrate stress systems. We conclude that many unrelated insects share a baseline pathway of predator-induced stress responses that we refer to as the octopamine-adipokinetic hormone (OAH) axis. We also present best practices for studying predator-induced stress responses in prey insects. We encourage investigators to compare neurophysiological responses to predator-related stress at the organismal, neurohormonal, tissue, and cellular levels within and across taxonomic groups. Studying stress-response variation between ecological contexts and across taxonomic levels will enable the field to build a holistic understanding of, and distinction between, taxon- and stimulus-specific responses relative to universal stress responses.


Subject(s)
Insecta/physiology , Octopamine/metabolism , Stress, Physiological/physiology , Animals , Behavior, Animal/physiology , Food Chain , Insect Hormones/metabolism , Neurotransmitter Agents/metabolism , Predatory Behavior
18.
Front Neurosci ; 14: 134, 2020.
Article in English | MEDLINE | ID: mdl-32153356

ABSTRACT

SIFamides are a family of highly conserved neuropeptides in arthropods, and in insects are mainly expressed in four medial neurons in the pars intercerebralis of the brain. Although SIFamide has been shown to influence sexual behavior, feeding, and sleep regulation in holometabolous insects such as Drosophila melanogaster, little is known about its role in hemimetabolous insects, including the blood-sucking bug, Rhodnius prolixus. In this study, we confirm the nucleotide sequence for R. prolixus SIFamide (Rhopr-SIFa) and find characteristic phenotypic expression of SIFamide in four cells of the pars intercerebralis in the brain. In addition to extensive SIFa projections throughout the entire central nervous system, SIFamidergic processes also enter into the corpus cardiacum, and project along the dorsal vessel, suggestive of Rhopr-SIFa acting as a neurohormone. Physiologically, Rhopr-SIFamide induces dose-dependent increases in heartbeat frequency in vitro suggesting the presence of peripheral receptors, and thereby indicating Rhopr-SIFa is released to act upon peripheral targets. We also explore the function of Rhopr-SIFa in R. prolixus, specifically in relation to feeding, since R. prolixus is a blood-gorging insect and a vector for Chagas disease. The intensity of SIFamide-like staining in the neurons in the brain is diminished 2 h following feeding, and restocking of those cells is finished 24 h later, indicating Rhopr-SIFa may be released at feeding. The results of temporal qPCR analysis were consistent with the immunohistochemical findings, showing an increase in Rhopr-SIFa transcript expression in the brain 2 h after feeding. We also observed enhanced feeding (size of meal) in insects injected with Rhopr-SIFa whereas insects with RNAi-mediated knockdown of the Rhopr-SIFa transcript consumed a significantly smaller blood meal relative to controls. These data suggest that the four SIFamidergic neurons and associated arborizations may play an important function in the neuronal circuitry controlling R. prolixus feeding, with Rhopr-SIFa acting as a central and peripheral neuromodulator/neurohormone.

19.
Invert Neurosci ; 20(1): 2, 2020 01 24.
Article in English | MEDLINE | ID: mdl-31980901

ABSTRACT

Members of the decapod infraorder Achelata, specifically species from the genus Panulirus, have storied histories as models for investigating the basic principles governing the generation, maintenance, and modulation of rhythmic motor behavior, including modulation by locally released and circulating peptides. Despite their contributions to our understanding of peptidergic neuromodulation, little is known about the identity of the native neuropeptides and neuronal peptide receptors present in these crustaceans. Here, a Panulirus argus nervous system-specific transcriptome was used to help fill this void, providing insight into the neuropeptidome and neuronal peptide receptome of this species. A neuropeptidome consisting of 266 distinct peptides was predicted using the P. argus assembly, 128 having structures placing them into a generally recognized arthropod peptide family: agatoxin-like peptide, allatostatin A (AST-A), allatostatin B, allatostatin C, bursicon, CCHamide, crustacean cardioactive peptide, crustacean hyperglycemic hormone/molt-inhibiting hormone, diuretic hormone 31 (DH31), ecdysis-triggering hormone (ETH), FMRFamide-like peptide (FLP), glycoprotein hormone (GPH), GSEFLamide, inotocin, leucokinin, myosuppressin, natalisin, neuroparsin, neuropeptide F, orcokinin, orcomyotropin, periviscerokinin, pigment-dispersing hormone, pyrokinin, red pigment-concentrating hormone, RYamide, short neuropeptide F (sNPF), SIFamide, sulfakinin, tachykinin-related peptide (TRP), and trissin. Twenty-five putative neuronal receptors, encompassing 15 peptide groups, were also identified from the P. argus transcriptome: AST-A, bursicon, CCHamide, DH31, diuretic hormone 44, ETH, FLP, GPH, inotocin, insulin-like peptide, myosuppressin, natalisin, periviscerokinin, sNPF, and TRP. Collectively, the reported data provide a powerful resource for expanding studies of neuropeptidergic control of physiology and behavior in members of the genus Panulirus specifically, and decapods generally.


Subject(s)
Neuropeptides/metabolism , Palinuridae/physiology , Signal Transduction/physiology , Animals
20.
Anim Reprod Sci ; 208: 106122, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31405473

ABSTRACT

The vitellogenesis-inhibiting hormone (VIH), also known as gonad-inhibiting hormone, is a neuropeptide hormone in crustaceans that belongs to the crustacean hyperglycemic hormone (CHH)-family peptide. There is regulation vitellogenesis by VIH during gonad maturation in crustaceans. A full-length Scylla olivacea VIH (Scyol-VIH) was identified through reverse transcription polymerase chain reaction and rapid amplification of cDNA ends. The open reading frame consists of 378 nucleotides, which encodes a 126-amino acid precursor protein, including a 22-residue signal peptide and a 103-amino acid mature peptide in which 6 highly conserved cysteine residues are present. There was expression of the Scyol-VIH gene in immature female Scylla olivacea in the eyestalk, brain and ventral nerve cord. The Scyol-VIH gene expression was localized to the eyestalk X-organ, brain neuronal clusters 6 and 11, and in multiple neuronal clusters of the ventral nerve cord. The relative abundance of Scyol-VIH mRNA transcript in the eyestalk was relatively greater in immature stage females, then decreased as ovarian maturation progressed. Furthermore, eyestalk Scyol-VIH increased after dopamine (5 µg/g BW) injection. The present research provides fundamental information about Scyol-VIH and its potential effect in controlling reproduction.


Subject(s)
Brachyura/physiology , Dopamine/pharmacology , Invertebrate Hormones/metabolism , Ovary/growth & development , RNA, Messenger/metabolism , Amino Acid Sequence , Animals , Base Sequence , Brachyura/genetics , Cloning, Molecular , Dopamine/administration & dosage , Dopamine Agents/pharmacology , Dopamine Antagonists/administration & dosage , Dopamine Antagonists/pharmacology , Female , Gene Expression Regulation/drug effects , Invertebrate Hormones/genetics , Ovary/metabolism , Phylogeny , RNA, Messenger/genetics , Serotonin/administration & dosage , Serotonin/pharmacology , Serotonin Agents/administration & dosage , Serotonin Agents/pharmacology , Sexual Maturation , Spiperone/administration & dosage , Spiperone/pharmacology , Time Factors
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