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Introduction: Secretoneurin (SN) is a novel biomarker that provides prognostic information in patients with cardiovascular disease. In experimental models, SN production is increased in the failing myocardium. Currently, no information is available on SN production in human myocardium. Accordingly, we wanted to determine the trans-cardiac gradient of SN in patients with Takotsubo syndrome (TTS), and to correlate circulating SN concentrations with indices of cardiac structure and function. Methods: We included 15 women diagnosed with TTS according to established criteria. Plasma SN concentrations were measured in blood samples obtained simultaneously from the aortic root and the coronary sinus. Coronary physiology was assessed by invasive measurements, and we used cardiac magnetic resonance imaging to determine left ventricular ejection fraction (LVEF) and cardiac mass. Results: Median age was 65 years and median LVEF was 45%. Median SN concentration was 39 (25th–75th percentile 31–44) pmol/L in the coronary sinus and 37 (30–41) pmol/L in the aortic root (p = 0.02 for difference). SN concentrations in the aortic root showed the highest correlations with N-terminal B-type natriuretic peptide (rho = 0.47) and estimated glomerular filtration rate (rho = −0.41). In contrast, we found weak correlations between SN concentrations and index of myocardial resistance (rho = 0.12), LVEF (rho = 0.08), and cardiac mass (rho = −0.09). Conclusion: We demonstrate a positive trans-cardiac gradient of SN in patients with TTS, which supports the hypothesis that SN is produced and released in the human myocardium in situations of myocardial dysfunction and stress. [ABSTRACT FROM AUTHOR]

In this study, the complex organization of the AnG in the giant freshwater prawn Macrobrachium rosenbergii was revealed using various techniques, including conventional histology, histochemistry, scanning electron microscopy, and X-ray tomography. The results showed the diversity of cells in the AnG and the detailed organization of the labyrinth's tubule into four radiated areas from the central to peripheral zones. The study also demonstrated the expression of some vertebrate kidney-associated homolog genes, aquaporin (AQP), solute carrier family 22 (SLC-22), nephrin, and uromodulin, in the AnG by qPCR. The result of in situ hybridization further showed the localization of SLC-22 and AQP transcript in the bladder and labyrinth's epithelium, specifically in regions 2, 3, and 4. Additionally, the study revealed neuropeptide expressions in the AnG by qPCR and in situ hybridization, i.e., crustacean hyperglycemic hormone (CHH) and molt inhibiting hormone (MIH), implying that the AnG may have a role in hormone production. Moreover, male and female prawns exhibited different levels of AQP, SLC-22, nephrin, and CHH expressions during the premolt and intermolt stages, suggesting a crucial role relevant to the molting stages. In conclusion, this study clarified the complex structure of the AnG in M. rosenbergii and demonstrated for the first time the expression of vertebrate kidney-associated genes and the possible endocrine role of the AnG. Further investigation is needed to clarify the role of these genes, particularly during ecdysis. The implications of these findings could significantly advance our understanding of the AnG in decapod crustaceans. [ABSTRACT FROM AUTHOR]

BackgroundThe behavior of the comprehensive circulating renin-angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored.Hypothesis/objectivesThe classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD.AnimalsOne-hundred seventeen client-owned dogs (normal = 60; B1 = 31; B2 = 26).MethodsProspective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs.ResultsCore RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2surr ) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4-2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P

Reptiles display considerable diversity in reproductive behavior, making them great models to study the neuroendocrine control of reproductive behavior. Many reptile species are seasonally breeding, such that they become reproductively active during their breeding season and regress to a nonreproductive state during their nonbreeding season, with this transition often prompted by environmental cues. In this review, we will focus on summarizing the neural and neuroendocrine mechanisms controlling reproductive behavior. Three major areas of the brain are involved in reproductive behavior: the preoptic area (POA), amygdala, and ventromedial hypothalamus (VMH). The POA and VMH are sexually dimorphic areas, regulating behaviors in males and females respectively, and all three areas display seasonal plasticity. Lesions to these areas disrupt the onset and maintenance of reproductive behaviors, but the exact roles of these regions vary between sexes and species. Different hormones influence these regions to elicit seasonal transitions. Circulating testosterone (T) and estradiol (E2) peak during the breeding season and their influence on reproduction is well‐documented across vertebrates. The conversion of T into E2 and 5α‐dihydrotestosterone can also affect behavior. Melatonin and corticosterone have generally inhibitory effects on reproductive behavior, while serotonin and other neurohormones seem to stimulate it. In general, there is relatively little information on the neuroendocrine control of reproduction in reptiles compared to other vertebrate groups. This review highlights areas that should be considered for future areas of research. Research highlights: Reptiles display considerable diversity in reproductive behavior yet are a relatively understudied group.Reptile reproduction is driven by interactions between brain regions and hormones.Reptilian reproduction is complex, and more research is needed to identify mechanisms across species. [ABSTRACT FROM AUTHOR]

The endocrine cells of the pituitary gland are electrically active, and in vivo they form small networks where the bidirectional cell-cell coupling is through gap junctions. Numerous studies of dispersed pituitary cells have shown that typical behaviors are tonic spiking and bursting, the latter being more effective at evoking secretion. In this article, we use mathematical modeling to examine the dynamics of small networks of spiking and bursting pituitary cells. We demonstrate that intrinsic bursting cells are capable of converting intrinsic spikers into bursters, and perform a fast/slow analysis to show why this occurs. We then demonstrate the sensitivity of network dynamics to the placement of bursting cells within the network, and demonstrate strategies that are most effective at maximizing secretion from the population of cells. This study provides insights into the in vivo behavior of cells such as the stress-hormone-secreting pituitary corticotrophs that are switched from spiking to bursting by hypothalamic neurohormones. While much is known about the electrical properties of these cells when isolated from the pituitary, how they behave when part of an electrically coupled network has been largely unstudied. [ABSTRACT FROM AUTHOR]

Insect vitellogenins are an intriguing class of complex proteins. They primarily serve as a source of energy for the developing embryo in insect eggs. Vitellogenesis is a complex hormonally and neurally controlled process that command synthesis of vitellogenin molecules and ensures their transport from the female fat bodies or ovarial cells into eggs. The representatives of all insect hormones such as juvenile hormones, ecdysteroids, and neurohormones participate in vitellogenesis, but juvenile hormones (most insect species) and ecdysteroids (mostly Diptera) play the most important roles in the process. Strikingly, not only insect females, but also males have been reported to synthesize vitellogenins indicating their further utility in the insect body. Indeed, it has recently been found that vitellogenins perform a variety of biological functions in the insect body. They participate in defense reactions against entomopathogens such as nematodes, fungi, and bacteria, as well as against venoms such as the honeybee Apis mellifera venom. Interestingly, vitellogenins are also present in the venom of the honeybee itself, albeit their exact role is unknown; they most likely increase the efficacy of the venom in the victim's body. Within the bee's body vitellogenins contribute to the lifespan regulation as antiaging factor acting under tight social interactions and hormonal control. The current minireview covers all of these functions of vitellogenins and portrays them as biologically active substances that play a variety of significant roles in both insect females and males, and not only acting as passive energy sources for developing embryo. [ABSTRACT FROM AUTHOR]

Long-term relationships are essential for the psychological wellbeing of humans and many animals. Positive emotions and affective experiences (e.g., romantic or platonic love) seem to be closely related to the creation and maintenance of social bonds. When relationships are threatened or terminated, other emotions generally considered to be negative can arise (e.g., jealousy or loneliness). Because humans and animals share (to varying degrees) common evolutionary histories, researchers have attempted to explain the evolution of affect and emotion through the comparative approach. Now brain imaging techniques allow the comparison of the neurobiological substrates of affective states and emotion in human and animal brains using a common methodology. Here, we review brain imaging studies that feature emotions characterized by the context of social bonding. We compare imaging findings associated with affective and emotional states elicited by similar social situations between humans and animal models. We also highlight the role of key neurohormones (i.e., oxytocin, vasopressin, and dopamine) that jointly support the occurrence of socially contextualized emotions and affect across species. In doing so, we seek to explore and clarify if and how humans and animals might similarly experience social emotion and affect in the context of social relationships.

Lifestyle modification can lead to numerous health issues closely associated with sleep. Sleep deprivation and disturbances significantly affect inflammation, immunity, neurodegeneration, cognitive depletion, memory impairment, neuroplasticity, and insulin resistance. Sleep significantly impacts brain and memory formation, toxin excretion, hormonal function, metabolism, and motor and cognitive functions. Sleep restriction associated with insulin resistance affects these functions by interfering with the insulin signalling pathway, neurotransmission, inflammatory pathways, and plasticity of neurons. So, in this review, We discuss the evidence that suggests that neurodegeneration occurs via sleep and is associated with insulin resistance, along with the insulin signalling pathways involved in neurodegeneration and neuroplasticity, while exploring the role of hormones in these conditions. Highlights: Insulin resistance increases the accumulation of amyloid β, tau, and synuclein in neurons, leading to neurodegeneration. The insulin signalling pathway has a potential role in sleep deprivation-induced insulin resistance. Neurohormones that play a role in the sleep/wake cycle modulate insulin sensitivity, metabolism, and neurodegeneration. [ABSTRACT FROM AUTHOR]

A map of central nervous system organization based on vascular networks provides a layer of organization distinct from familiar neural networks or connectomes. As a well‐established example, the capillary networks of the pituitary portal system enable a route for small amounts of neurochemical signals to reach local targets by traveling along specialized pathways, thereby avoiding dilution in the systemic circulation. The first evidence of such a pathway in the brain came from anatomical studies identifying a portal pathway linking the hypothalamus and the pituitary gland. Almost a century later, we demonstrated a vascular portal pathway that joined the capillary beds of the suprachiasmatic nucleus and a circumventricular organ, the organum vasculosum of the lamina terminalis, in a mouse brain. For each of these portal pathways, the anatomical findings opened many new lines of inquiry, including the determination of the direction of flow of information, the identity of the signal that flowed along this pathway, and the function of the signals that linked the two regions. Here, we review landmark steps to these discoveries and highlight the experiments that reveal the significance of portal pathways and more generally, the implications of morphologically distinct nuclei sharing capillary beds. [ABSTRACT FROM AUTHOR]

Abstract Background The behavior of the comprehensive circulating renin‐angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored. Hypothesis/Objectives The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD. Animals One‐hundred seventeen client‐owned dogs (normal = 60; B1 = 31; B2 = 26). Methods Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs. Results Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2surr) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4‐2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P

The aim of the present study was to determine the effects of alcohol intoxication and withdrawal on hypothalamic neurohormones such as corticotropin-releasing factor (CRF) and arginine vasopressin (AVP), and extrahypothalamic neurotransmitters such as striatal dopamine (DA), amygdalar gamma aminobutyric acid (GABA), and hippocampal glutamate (GLU). In addition, the participation of the two CRF receptors, CRF1 and CRF2, was investigated. For this purpose, male Wistar rats were exposed to repeated intraperitoneal (ip) administration of alcohol every 12 h, for 4 days and then for 1 day of alcohol abstinence. On the fifth or sixth day, intracerebroventricular (icv) administration of selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B was performed. After 30 min, the expression and concentration of hypothalamic CRF and AVP, the concentration of plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT), and the release of striatal DA, amygdalar GABA, and hippocampal GLU were measured. Our results indicate that the neuroendocrine changes induced by alcohol intoxication and withdrawal are mediated by CRF1, not CRF2, except for the changes in hypothalamic AVP, which are not mediated by CRF receptors. [ABSTRACT FROM AUTHOR]

Yoga has been prevalent for over 5000 years; it originated in India and has become an essential lifestyle ingredient for achieving optimal health. The goal of this article in lifestyle modification is to increase awareness about the benefits of yoga and how its practice can reduce the overall risk of chronic diseases. Yoga has been proven to be therapeutic for enhancing immunity and support management of chronic diseases such as cardiovascular, respiratory, endocrine disorders, obesity, cancer, and metabolic syndrome. Yoga techniques called asanas, such as pranayama for breathing regulation and dhyana for meditation, boost innate immune response, interrupt inflammation, and thereby prevent the manifestation of chronic diseases. Yoga also provides symptomatic relief for chronic arthritis by increasing joint flexibility and microcirculation. Yoga and meditation regulate neurotransmitters, neuropeptides, hormones, and cytokines that mediate interactions between the central nervous system and the immune system. These techniques reduce the psychological and physiological effects of chronic stress. Serotonin, oxytocin, and melatonin released directly due to practicing yoga have been shown to better manage anxiety and fear, especially during the pandemic. We believe the current trends of chronic disease management will become more effective with the implementation of lifestyle changes using yoga. [ABSTRACT FROM AUTHOR]

The study of the small intestinal microbiota in humans is complicated due to the low availability of biomaterial. Non-invasive methods of metabolomics and bioinformatic data analysis can expand our understanding of the small intestinal microbiota structure and its role in maintaining body homeostasis. Here we assess the trajectory of age-related changes in the small intestinal microbial community of healthy individuals in the context of metaorganism-wide interaction between cytokine and neuroendocrine systems, by using the methods of gas chromatography mass spectrometry of microbial markers (GCMS MM) and optimal scaling. 110 apparently healthy children, adults and elderly individuals were enrolled to the study. The main types of the small intestine microbiota (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Fusobacteria) were quantified in peripheral blood by the GCMS MM method. To construct age-related trajectories of changes in the small intestinal microbiota and parameters of cytokine and neuroendocrine systems, the optimal scaling technique based on the multivariate Gifi transformation (CATPCA method) was used. It was found, that the small intestinal bacterial community of both children and seniors contained significantly lowered total number of microorganisms due to the low number of bacteria of Firmicutes and Actinobacteria types along with high number of members of Proteobacteria and Fusobacteria types compared with adults. Assessment of the trajectory of age-associated changes in microbiota of the small intestine showed that 1) children have strong dynamic fluctuations in the number and links within microbial community along with formation of links between the main regulatory immune and neuroendocrine systems of the metaorganism, 2) adults display plasticity and consistency in functioning of immune and nervous systems that determine the state of dynamic balance of the small intestinal microbiota, 3) healthy aging is characterized by high degree of cooperation between the main members of the bacterial community, which ensures system stability at new level, as one of the mechanisms of host adaptation. Thus, using methods of GCMS MM and optimal scaling, allows us to expand our understanding about age-associated trajectory of changes in the small intestinal microbiota and its cooperation with immune and neuroendocrine systems within the metaorganism, which can be used to develop new methods of therapy for infectious and non-infectious diseases.

AimsThe direct renin inhibitor, aliskiren, is known to reduce plasma renin activity (PRA), but whether the efficacy of aliskiren varies based on an individual's baseline PRA in patients hospitalized for heart failure (HF) is presently unknown. We characterized the prognostic value of PRA and determined if this risk is modifiable with use of aliskiren.Methods and resultsThis pre-specified neurohormonal substudy of ASTRONAUT analysed all patients hospitalized for HF with ejection fraction (EF) ≤40% with available baseline PRA data (n = 1306, 80.9%). Risk associated with baseline PRA and short-term changes in PRA from baseline to 1 month was modelled with respect to 12-month clinical events. Median baseline PRA was 3.0 (interquartile range 0.6-16.4) ng/mL/h. Aliskiren significantly reduced PRA early after treatment initiation through 12-month follow-up compared with placebo (P

Background: Functional hypothalamic amenorrhea (FHA) is a chronic endocrine disorder caused by the abnormal pulsatile secretion of neurohormones in the hypothalamus. Secretion of GnRH is regulated by kisspeptin/neurokinin B/dynorphin (KNDy) neurons. These neurons produce, among other neurohormones, neurokinin B (NKB) which regulates the coordinated stimulation or inhibition of GnRH secreting neurons. Aim of the study: Assessment and comparison of serum NKB in patients with FHA at baseline, and following 6 months of estrogen-progestagen therapy. Materials and methods: Fifty-five patients with functional hypothalamic amenorrhea were included in the study group. Serum concentrations of neurokinin B (NKB), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-β-estradiol (E2), prolactin (PRL), cortisol, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), fasting glucose and insulin, as well as lipid profile were measured at baseline. At the time of diagnosis, patients with FHA were prescribed a course of 2 mg 17-β-estradiol and 10 mg dydrogesterone for duration of 6 months. Serum NKB was then reassessed following treatment at 6 months. Results: At baseline, the FHA group was found to have a decreased serum NKB concentration when compared to a healthy control group. Following 6 months of sequential estrogen-progestogen hormone therapy, this study did not find any statistically significant difference in serum NKB concentration in the treatment arm compared to baseline. Conclusions: For the first time, NKB secretion has been studied in patients with FHA. A significantly lower level of serum NKB was observed in these patients at baseline, when compared to a control group. After 6 months of combination estrogen-progesterone therapy, no significant changes in NKB levels were observed in these patients. These findings, for the first time in the literature, provide insight into the perceived benefit of HRT, calling into question its benefit in addressing the underlying etiopathogenetic contributors of FHA. These new findings may contribute to more targeted and appropriate treatment of such patients in the future. [ABSTRACT FROM AUTHOR]

Each cerebral hemisphere is functionally connected to the contralateral side of the body through the decussating neural tracts. The crossed neural pathways set a basis for contralateral effects of brain injury such hemiparesis and hemiplegia as it has been already noted by Hippocrates. Recent studies demonstrated that, in addition to neural mechanisms, the contralateral effects of brain lesions are mediated through the humoral pathway by neurohormones that produce either the left or right side-specific effects. The side-specific humoral signaling defines whether the left or right limbs are affected after a unilateral brain injury. The hormonal signals are released by the pituitary gland and may operate through their receptors that are lateralized in the spinal cord and involved in the side-specific control of symmetric neurocircuits innervating the left and right limbs. Identification of features and a proportion of neurological deficits transmitted by neurohormonal signals vs. those mediated by neural pathways is essential for better understanding of mechanisms of brain trauma and stroke and development of new therapies. In a biological context, the left–right side-specific neuroendocrine signaling may be fundamental for the control of the left- and right-sided processes in bilaterally symmetric animals. [ABSTRACT FROM AUTHOR]

Long-term relationships are essential for the psychological wellbeing of humans and many animals. Positive emotions and affective experiences (e.g., romantic or platonic love) seem to be closely related to the creation and maintenance of social bonds. When relationships are threatened or terminated, other emotions generally considered to be negative can arise (e.g., jealousy or loneliness). Because humans and animals share (to varying degrees) common evolutionary histories, researchers have attempted to explain the evolution of affect and emotion through the comparative approach. Now brain imaging techniques allow the comparison of the neurobiological substrates of affective states and emotion in human and animal brains using a common methodology. Here, we review brain imaging studies that feature emotions characterized by the context of social bonding. We compare imaging findings associated with affective and emotional states elicited by similar social situations between humans and animal models. We also highlight the role of key neurohormones (i.e., oxytocin, vasopressin, and dopamine) that jointly support the occurrence of socially contextualized emotions and affect across species. In doing so, we seek to explore and clarify if and how humans and animals might similarly experience social emotion and affect in the context of social relationships. [ABSTRACT FROM AUTHOR]

Long-term relationships are essential for the psychological wellbeing of humans and many animals. Positive emotions and affective experiences (e.g., romantic or platonic love) seem to be closely related to the creation and maintenance of social bonds. When relationships are threatened or terminated, other emotions generally considered to be negative can arise (e.g., jealousy or loneliness). Because humans and animals share (to varying degrees) common evolutionary histories, researchers have attempted to explain the evolution of affect and emotion through the comparative approach. Now brain imaging techniques allow the comparison of the neurobiological substrates of affective states and emotion in human and animal brains using a common methodology. Here, we review brain imaging studies that feature emotions characterized by the context of social bonding. We compare imaging findings associated with affective and emotional states elicited by similar social situations between humans and animal models. We also highlight the role of key neurohormones (i.e., oxytocin, vasopressin, and dopamine) that jointly support the occurrence of socially contextualized emotions and affect across species. In doing so, we seek to explore and clarify if and how humans and animals might similarly experience social emotion and affect in the context of social relationships.

Introduction: Psychotic patients often require pharmacological treatment, which may prove ineffective, leading to treatment-resistant psychosis necessitating the use of clozapine. However, the emergence of side effects can result in discontinuation, potentially triggering a relapse of psychotic symptoms. One significant side effect is antipsychotic-induced weight gain which, over time, can lead to adverse metabolic events. Recent translational research is evaluating the impact of prenatal factors on the metabolic outcomes of psychotic patients, using a surrogate marker of the intrauterine milieu such as birth weight (BW). Objectives: We aim to evaluate the changes in leptin, adiponectin, and insulin levels in patients with treatment-resistant psychosis who initiate clozapine treatment due to persistent psychotic symptoms. Methods: Subjects older than 18 years with a diagnostic of a major mental disorder and initiating clozapine were enrolled in this 18-months longitudinal study. Neurohormones levels, including leptin, adiponeptin, and insulin were measured at baseline, 8 and 18 months during follow-up. Statistical analysis were conducted by using a fixed-effects model. Results: A total of 23 subjects initiating clozapine were evaluated during the initial mandatory 18-week period. Neurohormones, specifically leptin and adiponectin, were measured at three time points: baseline, 8 weeks, and 18 weeks. The changes in leptin levels were significantly associated with birth BW with sex differences, being inversely correlated only in females. Adiponectin was significantly associated with BW, being inversely correlated in males. Conversely, there was no observed association between insulin levels and BW. Conclusions: Our findings highlight the significance of prenatal factors in influencing the subsequent evolution of neurohormones in individuals initiating clozapine treatment. This suggests that subjects with lower BW tend to exhibit elevated neurohormone values, emphasizing the role of prenatal events in this context. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

The thalamic paraventricular nucleus (PVT) is a structure highly interconnected with several nuclei ranging from forebrain to hypothalamus and brainstem. Numerous rodent studies have examined afferent and efferent connections of the PVT and their contribution to behavior, revealing its important role in the integration of arousal cues. However, the majority of these studies used a region‐oriented approach, without considering the neuronal subtype diversity of the nucleus. In the present study, we provide the anatomical and transcriptomic characterization of a subpopulation of PVT neurons molecularly defined by the expression of glucokinase (Gck). Combining a genetically modified mouse model with viral tracing approaches, we mapped both the anterograde and the retrograde projections of Gck‐positive neurons of the anterior PVT (GckaPVT). Our results demonstrated that GckaPVT neurons innervate several nuclei throughout the brain axis. The strongest connections are with forebrain areas associated with reward and stress and with hypothalamic structures involved in energy balance and feeding regulation. Furthermore, transcriptomic analysis of the Gck‐expressing neurons revealed that they are enriched in receptors for hypothalamic‐derived neuropeptides, adhesion molecules, and obesity and diabetes susceptibility transcription factors. Using retrograde labeling combined with immunohistochemistry and in situ hybridization, we identify that GckaPVT neurons receive direct inputs from well‐defined hypothalamic populations, including arginine‐vasopressin‐, melanin‐concentrating hormone‐, orexin‐, and proopiomelanocortin‐expressing neurons. This detailed anatomical and transcriptomic characterization of GckaPVT neurons provides a basis for functional studies of the integration of homeostatic and hedonic aspects of energy homeostasis, and for deciphering the potential role of these neurons in obesity and diabetes development. [ABSTRACT FROM AUTHOR]

The cuttlefish (Sepia officinalis) is a Cephalopod mollusk that lives in the English Channel and breeds in coastal spawning grounds in spring. A previous work showed that the control of egg-laying is monitored by different types of regulators, among which neuropeptides play a major role. They are involved in the integration of environmental cues, and participate in the transport of oocytes in the genital tract and in the secretion of capsular products. This study addresses a family of neuropeptides recently identified and suspected to be involved in the control of the reproduction processes. Detected by mass spectrometry and immunocytochemistry in the nerve endings of the accessory sex glands of the females and ovary, these neuropeptides are also identified in the hemolymph of egg-laying females demonstrating that they also have a hormone-like role. Released in the hemolymph by the sub-esophageal mass, a region that innervates the genital tract and the neurohemal area of the vena cava, in in vitro conditions these neuropeptides modulated oocyte transport and capsular secretion. Finally, in silico analyses indicated that these neuropeptides, initially called FLGamide, had extensive structural homology with orcokinin B, which motivated their name change. [ABSTRACT FROM AUTHOR]

The genome of the sheep scab mite, Psoroptes ovis, was analysed for the presence of neuropeptide and neurohormone precursors and their G protein-coupled receptors (GPCRs). Many of these showed significant similarities to those known or predicted from other Acaridae and also insect species. Similarities to orthologous precursors and receptors from the sheep Ovis aries, host for P. ovis, were also evaluated. The roles of neuropeptides and neurohormones in the control of behavioural and physiological processes such as osmoregulation, reproduction, growth and development are discussed. The GPCRs for these neuropeptides and neurohormones offer potential targets for the development of next-generation acaricides. Modification of normal receptor function by new chemistries that either block or over-stimulate the GPCRs can result in the death of the mite or alter its normal development and reproductive ability thereby suppressing populations. This work provides the information required to select potential GPCR targets in P. ovis for future development of new acaricides. [ABSTRACT FROM AUTHOR]

[Display omitted] Heart failure (HF) is a major global health problem afflicting millions worldwide. Despite the significant advances in therapies and prevention, HF still carries very high morbidity and mortality, requiring enormous healthcare-related expenditure, and the search for new weapons goes on. Following initial treatment strategies targeting inotropism and congestion, attention has focused on offsetting the neurohormonal overactivation and three main therapies, including angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor antagonists, β-adrenoceptor antagonists, and mineralocorticoid receptor antagonists, have been the foundation of standard treatment for patients with HF. Recently, a paradigm shift, including angiotensin receptor-neprilysin inhibitor, sodium glucose co-transporter 2 inhibitor, and ivabradine, has been added. Moreover, soluble guanylate cyclase stimulator, elamipretide, and omecamtiv mecarbil have come out as a next-generation therapeutic agent for patients with HF. Although these pharmacologic therapies have been significantly successful in relieving symptoms, there is still no complete cure for HF. We may be currently entering a new era of treatment for HF with animal experiments and human clinical trials assessing the value of antibody-based immunotherapy and gene therapy as a novel therapeutic strategy. Such tempting therapies still have some challenges to be addressed but may become a weighty option for treatment of HF. This review article will compile the paradigm shifts in HF treatment over the past dozen years or so and illustrate current landscape of antibody-based immunotherapy and gene therapy as a new therapeutic algorithm for patients with HF. [ABSTRACT FROM AUTHOR]

Neurohormonal activation has never been investigated in patients with cardiac amyloidosis (CA). Forty-seven patients with amyloid light-chain (AL)-CA and 61 with transthyretin (ATTR)-CA were matched to non-amyloidotic heart failure (HF) patients based on age, sex, left ventricular ejection fraction ranges, renal function and HF therapies. N-terminal pro-B-type natriuretic peptide (NT-proBNP), norepinephrine and renin were dosed. The primary and secondary endpoints were 1-year cardiovascular death or HF hospitalisation, and 5-year cardiovascular death, respectively. Patients with AL-CA had a 10-fold higher NT-proBNP than HF patients (6548 ng/L [2059–15,097] vs. 692 [243–2241], p < 0.001), and slightly higher norepinephrine (595 ng/L [383–869] vs. 416 [250–693], p = 0.047). Patients with ATTR-CA had higher NT-proBNP (3984 ng/L [2275–9505] vs. 1751 [470–4768], p = 0.006), norepinephrine (552 ng/L [344–855] vs. 441 [323–601], p = 0.020), and renin (14 mU/L [8–80] vs. 10 [4–34], p = 0.017). Patients with AL- or ATTR-CA had more often 2 or 3 neurohormones above the corresponding upper reference limits than matched HF patients. NT-proBNP and aldosterone were univariate predictors of the primary endpoint in patients with ATTR-CA, but not in matched controls. NT-proBNP and renin predicted the secondary endpoint in patients with AL-CA, but not in matched controls. Patients with CA display a neurohormonal activation, with some prognostic significance. [ABSTRACT FROM AUTHOR]

According to new views on communication ways and principles in the main regulatory systems of the body, i.e., immune and neuroendocrine, there is a risk for disintegration of pathways and structures in these systems which may underlie disorders such as autism-spectrum disorders (ASD) and schizophreniaspectrum disorders (SSD). Both disorders are classified as neurodevelopmental disorders, with unclear etiology and partially overlapping pathophysiological developmental mechanisms. Diagnosis of ASD and SSD is based on patterns of clinical symptoms/syndromes that demonstrate high heterogeneity and similarity. Therefore, it is very important to find the ways of discerning children with ASD from those with SSD. Our aim was to identify peripheral activity indexes for immune and neuroendocrine systems, and their integration for usage as information hubs of congruency and phenotypic plasticity of these systems in children with ASD, as compared to SSD patients. The levels of 14 indexes of the immune and neuroendocrine systems in blood plasma were determined in 82 children with ASD, 9 children with SSD and 45 children with typical neurodevelopment (TD). To assess peripheral activity of the immune and neuroendocrine systems and their relationships, we applied a multivariate exploratory analysis using a method of nonlinear principal components. The following results were obtained: (1) absence of differences in proinflammatory cytokines between ASD and TD children; (2) patients with SSD have significantly higher values of IL-6 and IFNγ, and lower values of IL-1β, TNFα and IL-10 in blood plasma compared to children with ASD and TRD; (3) the level of neurohormones in children with ASD is in accordance with physiological reference values. The children with SSD have lower levels of epynephrine and dopamine compared to ASD and TD, respectively; (4) integration degree of regulatory systems assessed by principal component analysis has shown the following: (4.1) TD children have strong correlations within each of the systems and between them, thus showing their communicative abilities and plasticity, characteristic of normal values; (4.2) In SSD children, minimal numbers of strong relations were demonstrated within the cytokine system; (4.3) The children with ASD exhibited two clusters: one of them had a complete similarity with TDC, in terms of tension and assortment of immune and neuroendocrine indices; the other one presented low coupling between the parameters of regulatory systems, similar to the children with SSD; (4.4) Analysis of peripheral indices of cytokine and neuroendocrine systems for clusters 1 and 2 in children with ASD compared to children with SSD and TD demonstrated that, in children with ASD of cluster 1, the indices did not differ from TDC, except of epinephrine, ACTH, kynurenine, and tryptophan. In the children with ASD of cluster 2, the values of the indices are equal to children with SSD, except of dopamine and tryptophan. Thus, we have shown phenomenon of transdiagnostic clustering, i.e., allocation of two clusters among ASD children. One of them is similar to levels of indices and connections between the immune and neuroendocrine systems with TD, and another cluster is similar to SSD children. Therefore, they could be potentially useful as diagnostic criteria when discriminating the two disorders.

The extensive information accumulated over the past few decades on the important role of cerebrospinal fluid in many physiological processes in norm and pathology allowed the authors of the paper to express a hypothesis that the brain has its own endocrine system, which is represented by (a) brain neurons secreting neurohormones into the ventricles, (b) cerebrospinal fluid, a body fluid that ensures the delivery of neurohormones to the brain target regions, and (c) neurons of the periventricular region of the brain, targets for neurohormones contained in the cerebrospinal fluid. According to this hypothesis, the functional significance of the endocrine system of the brain in ontogenesis moves from the regulation of the neuron and brain development in the perinatal period to participation in volume neurotransmission in adulthood. This study is aimed at testing this hypothesis. Thus, in neonatal (fifth day of life) and adult (30th day of life) rats, it was shown that substances contained in the cerebrospinal fluid are involved in the regulation of monoamine secretion by brain neurons into the cerebrospinal fluid. These data were obtained by perfusion of cerebral ventricles with artificial cerebrospinal fluid with an increased content of K+. However, stimulation of the secretion of monoamines was not found in all animals within each age group, which is explained by the individual and age-related characteristics of the cerebrospinal fluid-brain barrier permeability. Indeed, perfusion of brain slices in the incubation medium with an increased content of K+ (in the absence of a cerebrospinal fluid-brain barrier) invariably led to the stimulation of monoamine secretion in all animals in both age groups. The second proof of the validity of our hypothesis was the demonstration of the uptake of substances from the cerebrospinal fluid into monoaminergic neurons of the brain, which are considered as potential targets for the endocrine factors of the cerebrospinal fluid. Evidence of this was obtained with the introduction into the cerebral ventricles of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide, which has a high affinity for monoamine transporters. After intraventricular administration, this marker was incorporated into neurons in the periventricular region of the brain. Thus, evidence has been obtained that the substances contained in the cerebrospinal fluid in neonatal and adult rats are involved in the regulation of the secretion of monoamines in the cerebral ventricles, and monoamines contained in the cerebrospinal fluid enter the brain and are captured by potential target neurons. [ABSTRACT FROM AUTHOR]

The endosymbiont Wolbachia feminises male isopods by making them refractory to the insulin‐like masculinising hormone, which shunts the autocrine development of the androgenic glands. It was, therefore, proposed that Wolbachia silences the IR receptors, either by preventing their expression or by inactivating them. We describe here the two IR paralogs of Armadillidium vulgare. They displayed a conventional structure and belonged to a family widespread among isopods. Av‐IR1 displayed an ubiquist expression, whereas the expression of Av‐IR2 was restricted to the gonads. Both were constitutively expressed in males and females and throughout development. However, upon silencing, altered gland physiology and gene expression therein suggested antagonistic roles for Av‐IR1 (androinhibiting) and Av‐IR2 (androstimulating). They may function in tandem with regulating neurohormones, as a conditional platform that conveys insulin signalling. Wolbachia infection did not alter their expression patterns: leaving the IRs unscathed, the bacteria would suppress the secretion of the neurohormones, thus inducing body‐wide IR deactivation and feminisation. Adult males injected with Wolbachia acquired an intersexed physiology. Their phenotypes and gene expressions mirrored the silencing of Av‐IR1 only, suggesting that imperfect feminisation stems from a flawed invasion of the androstimulating centre, whereas in fully feminised males invasion would be complete in early juveniles. Take Away: Two antagonistic Insulin Receptors were characterised in Armadillidium vulgare.The IRs were involved in androstimulating and androinhibiting functions.Wolbachia‐induced feminisation did not prevent the expression of the IRs.Imperfectly feminised intersexes phenocopied the silencing of Av‐IR1 only.Wolbachia would deactivate the IRs by suppressing neurosecretory co‐factors. [ABSTRACT FROM AUTHOR]

Primary open angle glaucoma is associated with an increased risk of mood and sleep disorders. These adversities have been suggested to relate to a disrupted function of the intrinsically photosensitive retinal ganglion cells (ipRGCs). The ipRGCs are key components in the nonvisual photoreceptive system that mediates light effects on mood, sleep and circadian rhythm. We assessed the diurnal hormone levels, pupillary responses and mood and sleep under seasons with different photoperiods in 24 patients with glaucoma and 24 age- and sex-matched healthy controls to investigate responses to naturalistic seasonal changes in daylight. The patients had moderate-to-advanced glaucoma with substantial visual field defects and reductions in the ipRGC-mediated pupillary responses (p <.001). In winter, compared with summer, patients with glaucoma had higher daytime melatonin concentration (p <.001) and lower nighttime cortisol (p =.002). In winter, the daytime melatonin level was inversely correlated with the ipRGC-mediated pupillary responses in the control group (p =.04). In the control group, there were no significant changes in hormone levels between seasons or any correlations between neurohormone levels and the ipRGC-mediated responses. The two groups showed a similar response to season with lower depression scores in summer compared with winter. In between-group comparison, the nocturnal melatonin level (area under curve from 20:00 h to 08:00 h) in summer was lower in glaucoma compared with controls (p =.03). In winter, nocturnal cortisol (at 04:00 h) was lower (p =.004) and daytime cortisol (12:00 h and 16:00 h) was higher (p =.007) in glaucoma compared with controls. In conclusion, we found that patients with glaucoma displayed a seasonal variation in diurnal hormone levels that was not present in healthy controls. Such neurohormonal changes may contribute to the increased risk of mood and sleep disorders seen in patients with glaucoma. [ABSTRACT FROM AUTHOR]

Background/Objectives: Neurohormonal therapy, which includes beta‐blockers and angiotensin‐converting enzyme inhibitor/angiotensin receptor blockers (ACEi/ARBs), is the cornerstone of heart failure with reduced ejection fraction (HFrEF) treatment. While neurohormonal therapies have demonstrated efficacy in randomized clinical trials, older patients, which now comprise the majority of HFrEF patients, were underrepresented in those original trials. This study aimed to determine the association between short‐ (30 day) and long‐term (1 year) mortality and the use of neurohormonal therapy in HFrEF patients, across the age spectrum. Design/Setting/Participants: This is a population‐based, retrospective, cohort study between January 2008 and December 2015. We used 100% Medicare Parts A and B and a random 40% sample of Part D to create a cohort of 295,494 fee‐for‐service beneficiaries with at least one hospitalization for HFrEF between 2008 and 2015. All analyses were performed between May 2019 and July 2020. Exposure We used Part D data to determine exposure to beta‐blocker and ACEi and ARB therapy. Results: We found that in 295,494 patients admitted for HFrEF between 2008 and 2015, the average age was 80 years, 54% were female and 17% were non‐white. The baseline mortality rate was higher among those aged ≥85, but the mortality benefits of neurohormonal therapy were preserved across the age spectrum. Among those ≥85 years old, the hazard ratio for death within 30 days was 0.59 (95% confidence interval [CI] 0.56–0.62; p < 0.001) for beta‐blockers and 0.47 (95% CI 0.44–0.49; p < 0.001) for ACEi/ARBs. The hazard ratio for death within 1 year was 0.37–0.56 (95% CI 0.35–0.58; p < 0.001) for beta‐blockers and 0.38–0.53 (95% CI 0.37–0.55; p < 0.001) for ACEi/ARB. Conclusion: At a population level, neurohormonal therapy was associated with lower short‐ and long‐term mortality across the age spectrum. [ABSTRACT FROM AUTHOR]

Depression is one of the world’s most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother–child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine’s clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother–infant bond early in the offspring’s life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals’ cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity.

Rhodnius prolixus (the kissing bug and a major vector of Chagas disease) is an obligate blood feeder that in the case of the fifth instar consumes up to 10 times its unfed body weight in a single 20-minute feed. A post-prandial diuresis is initiated, within minutes of the start of gorging, in order to lower the mass and concentrate the nutrients of the meal. Thus, R. prolixus rapidly excretes a fluid that is high in NaCl content and hypo-osmotic to the hemolymph, thereby eliminating 50% of the volume of the blood meal within 3 hours of gorging. In R. prolixus, as with other insects, the Malpighian tubules play a critical role in diuresis. Malpighian tubules are not innervated, and their fine control comes under the influence of the neuroendocrine system that releases amines and neuropeptides as diuretic or antidiuretic hormones. These hormones act upon the Malpighian tubules via a variety of G protein-coupled receptors linked to second messenger systems that influence ion transporters and aquaporins; thereby regulating fluid secretion. Much has been discovered about the control of diuresis in R. prolixus, and other model insects, using classical endocrinological studies. The post-genomic era, however, has brought new insights, identifying novel diuretic and antidiuretic hormone-signaling pathways whilst also validating many of the classical discoveries. This paper will focus on recent discoveries into the neuroendocrine control of the rapid post-prandial diuresis in R. prolixus, in order to emphasize new insights from a transcriptome analysis of Malpighian tubules taken from unfed and fed bugs.

Evidence that neurohormones contribute to the contralateral effects of unilateral brain injury challenges a fundamental assumption of basic neuroscience and clinical neurology.

Brain injuries can interrupt descending neural pathways that convey motor commands from the cortex to spinal motoneurons. Here, we demonstrate that a unilateral injury of the hindlimb sensorimotor cortex of rats with completely transected thoracic spinal cord produces hindlimb postural asymmetry with contralateral flexion and asymmetric hindlimb withdrawal reflexes within 3 hr, as well as asymmetry in gene expression patterns in the lumbar spinal cord. The injury-induced postural effects were abolished by hypophysectomy and were mimicked by transfusion of serum from animals with brain injury. Administration of the pituitary neurohormones β-endorphin or Arg-vasopressin-induced side-specific hindlimb responses in naive animals, while antagonists of the opioid and vasopressin receptors blocked hindlimb postural asymmetry in rats with brain injury. Thus, in addition to the well-established involvement of motor pathways descending from the brain to spinal circuits, the side-specific humoral signaling may also add to postural and reflex asymmetries seen after brain injury.