Neuroendocrine Regulation Research Articles

Effects of multidisciplinary therapy on energy balance, inflammation, and metabolic diseases in adolescents with obesity: A narrative review.

Obesity is a consequence of multiple factors, including genetics, lifestyle and nutritional choices, physical activity, sleep duration, screen time, and mood disorders. These behavioral elements can impair the regulation of energy balance and obesity management that link obesity to a constellation of chronic conditions that lead to a high prevalence of cardiometabolic risk factors, metabolic syndrome, and nonalcoholic fatty liver disease. Multidisciplinary therapy is defined as an approach delivered by a multidisciplinary-trained health team covering at least two components of behavior, physical activity/exercise, dietary habits, and/or psychological counseling associated with clinical interventions. This narrative review summarizes the effects of multidisciplinary therapy on neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, metabolic syndrome, nonalcoholic fatty liver diseases, behavior, and quality of life. We found that multidisciplinary therapy, including medical, nutritional, exercise, and behavioral counseling, and/or education, was useful for addressing outcomes such as visceral adiposity, neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, nonalcoholic fatty liver disease, and metabolic syndrome. The effects were mediated by improvements in neuroendocrine regulation of energy balance, downregulation of the pro-inflammatory states, and a reduction in comorbidities. Multidisciplinary therapy also improved mood disorders and quality of life.

Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine

Recent studies have shown a growing interest in the complex relationship between the human gut microbiota, metabolism, and overall health. This review aims to explore the gut microbiota–host association, focusing on its implications for precision nutrition and personalized medicine. The objective is to highlight how gut microbiota modulate metabolic and immune functions, contributing to disease susceptibility and wellbeing. The review synthesizes recent research findings, analyzing key studies on the influence of gut microbiota on lipid and carbohydrate metabolism, intestinal health, neurobehavioral regulation, and endocrine signaling. Data were drawn from both experimental and clinical trials examining microbiota–host interactions relevant to precision nutrition. Our findings highlight the essential role of gut microbiota-derived metabolites in regulating host metabolism, including lipid and glucose pathways. These metabolites have been found to influence immune responses and gut barrier integrity. Additionally, the microbiota impacts broader physiological processes, including neuroendocrine regulation, which could be crucial for dietary interventions. Therefore, understanding the molecular mechanisms of dietary–microbiota–host interactions is pivotal for advancing personalized nutrition strategies. Tailored dietary recommendations based on individual gut microbiota compositions hold promise for improving health outcomes, potentially revolutionizing future healthcare approaches across diverse populations.

Seasonal changes in activity of hypothalamic thyroid hormone system in different winter phenotypes of Djungarian hamster (Phodopus sungorus).

Although the Djungarian hamster (Phodopus sungorus) is a seasonality model, it presents substantial variability in winter acclimation. In response to short photoperiod, some individuals express a suite of winter traits such as low body mass, regressed gonads, white fur, and daily torpor, while others develop only some adjustments or maintain a summer phenotype. Despite comprehensive research, the mechanisms underlying polymorphism of winter phenotype are still unknown. We compared key elements of the hypothalamic thyroid hormone system, as well as the tanycyte architecture in hamsters of both sexes. Individuals presented different responses to short photoperiod characterized either as phenotypes (non-responder, partial-responder and full-responder) or photoresponsive index. We measured the expression of genes coding iodothyronine deiodinase 2 and 3, monocarboxylate transporter 8, thyrotropin-releasing hormone, and somatostatin in 40 individuals and counted the number of immunolabeled tanycyte processes in standardized regions of interest around the third ventricle in 30 individuals. Animals acclimated to short photoperiod presented a downregulation of diodinase 2 and somatostatin and an upregulation of deiodinase 3, as well as a decreased number of tanycyte processes, compared to long photoperiod-exposed individuals. Although phenotypes did not differ in gene expression, the higher the photoresponsive index, the lower was the deiodinase 2 expression and the higher the deiodinase 3 expression. Partial-responders and full-responders had less tanycyte processes than non-responders, and the number of tanycyte processes correlated with the photoresponsive index. Sexes differed neither in their seasonal response, nor hypothalamic gene expression, but females had more tanycyte processes. Our results are in accordance with studies emphasizing the pivotal role of thyroid hormones in seasonal response. We suggest that the whole spectrum of winter phenotypes exists within the population of Djungarian hamsters and that it is reflected also at the level of neuroendocrine regulation. However, the neuroendocrine underpinnings of winter phenotype polymorphism require further investigation.

Immunological indicators of the risk of the transition from chronic gastritis to gastric ulcer in adolescents

As is known, gastric ulcer (GCC) and duodenal ulcer (duodenal ulcer) are chronic, complex-etiology diseases, the mechanism of which is based on complex transformations of nervous, hypothalamic-pituitary, hypothalamic-pituitary-adrenal and local gastroduodenal processes that lead to a change in trophism in the mucous membrane of the stomach and duodenum. In turn, the incipient ulcerative defect is a source of irritation of the enteric receptors, supporting disorders of neurohormonal regulation. Thus, the resulting “vicious circle” causes the chronic course of peptic ulcer disease. During the study of chronic diseases of gastroduodenal localization, including peptic ulcer disease, many doctrines of its occurrence have been proposed. However, the issue of the origin of peptic ulcer disease still remains insufficiently studied; approaches and tactics for managing patients with erosive and ulcerative lesions of the upper gastrointestinal tract are being developed. The aim of the study was to evaluate immunological indicators that determine the risk of chronic gastritis turning into gastric ulcer. The study included 120 children aged 14-17 years, permanently residing in the Bukhara region of the Republic of Uzbekistan. Taking into account the importance of H. Pylori in the development of HCG, patients were distributed depending on the association of HCG with H. Pylori. To study cytokines, blood tests of patients were performed to determine the titer of antibodies (IgG and IdM) to H. Pylori, immunoglobulins A, M, G in blood serum, secretory IgA in oral fluid, IL-1β, IL-10, TNFα, VEGF in the serum of patients. At the same time, blood sampling was carried out in the periods before and 3 weeks (21 days) after treatment. Thus, the study of the value of immunological blood parameters in the progression of HCG to gastric ulcer disease dictates the need to develop immunological indicators for predicting the progression of HCG to gastric ulcer in adolescents. An increase in TNFα levels indicates a high risk of developing gastric ulcer as a result of vascular damage and impaired local circulation. In the study, an established increase in the level of IL-1β indicates activation of the synthesis of proinflammatory cytokines in HCG, especially in HCG associated with H. Pylori. The use of these recommendations contributes to the monitoring of HCG, improving the effectiveness of diagnosis and the correct choice of treatment for patients with HCG, reducing mortality and disability at the same time.

Bending/force switching control of pneumatic soft actuator based on multi-sensor fusion

Abstract The soft actuator has unlimited freedom, and can realize the grasping of irregular or fragile objects. A pneumatic soft actuator is designed in this paper, which consists of a series of symmetrically distributed pneumatic chambers. The soft actuator consists of a top expansion layer composed of 20 chambers and a bottom restraint layer. The Yeoh model and the finite element method (FEM) were employed to analyze the bending of the soft actuator. To improve the tracking performance, a PID strategy of the endocrine system (ES-PID) based on the neuroendocrine thyroid hormone regulation mechanism was constructed to tune the bending deformation. To achieve steady and precise force control, a bending/force switching control algorithm based on multi-sensor fusion is designed to realize high control accuracy. The bending/force switching control strategy mainly consists of two feedback loops for bending control, a force control, and a switching control. In the experimental process, the bending control is the primary control, and the force control is the primary control when the switching condition is satisfied. In order to prevent the occurrence of a false switching action, a switching factor is constructed using the method of successive comparison of neighboring values. Finally, several experiments are carried out to verify the effectiveness and feasibility of the control algorithm.

Metabolic Syndrome in Reproductive Age Women of Various Ethnic Groups. Neuroendocrine Status and Lipid Peroxidation System.

We analyzed the state of neuroendocrine regulation and LPO-antioxidant defense systems in reproductive age women with metabolic syndrome (MetS), representatives of the Russian and Buryat ethnic groups. Compared to the corresponding control groups, women from the Russian ethnic group with MetS had elevated levels of thyroid-stimulating hormone and free androgen index (FAI) and reduced levels of sex hormone-binding globulin, while women from the Buryat ethnic group had increased levels of prolactin and FAI. Changes in the LPO system in women of the Russian ethnic group with MetS consisted in an increase in the levels of substrates with double bonds, TBA-reactive substances, and fat-soluble vitamins. Buryat women with MetS had a higher content of primary oxidation products and reduced levels of glutathione. The results of the study indicate a hyperandrogenic shift in the neuroendocrine regulation system, as well as compensatory influences from different parts of the antioxidant defense system in women of reproductive age with MetS, depending on their ethnicity. These findings indicate the need for assessing and monitoring the levels of these metabolites in women with MetS, considering their ethnicity.

Hormonal status in women with respiratory viral infections during critical periods

Pregnancy and menopause are critical periods in a woman’s life. Due to physiological changes in the neuroendocrine system regulation, susceptibility to respiratory viral infections increases in these periods, while affecting all organs and systems of the human body. The aim of this review was to analyze the literature data on the effect of acute respiratory viral infections on neuroendocrine regulation in women during pregnancy and menopause. We reviewed full-text publications in the public domain from the PubMed, eLibrary.ru, and Google Scholar databases with a coverage period of more than twenty years (2000–2023). Disruptions of the progesterone and estrogen production during infection with the influenza A (H1N1) and influenza B viruses have been shown in experimental studies. Hormonal status changes in pregnant women are detected during infection with the influenza A virus (H3N2) and depend on antiviral antibody titers and the presence of fetoplacental insufficiency. Pregnant women with COVID-19 may experience changes in the brain structure activities, as indicated by a high frequency of those in olfactory sensitivity and psychoemotional disorders. During menopause, infection with the SARS-CoV-2 virus leads to changes in the production of thyroxine, prolactin, estradiol, testosterone, cortisol, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate.

Characterization of Circulating Protein Profiles in Individuals with Prader–Willi Syndrome and Individuals with Non-Syndromic Obesity

Background: Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by distinctive physical, cognitive, and behavioral manifestations, coupled with profound alterations in appetite regulation, leading to severe obesity and metabolic dysregulation. These clinical features arise from disruptions in neurodevelopment and neuroendocrine regulation, yet the molecular intricacies of PWS remain incompletely understood. Methods: This study aimed to comprehensively profile circulating neuromodulatory factors in the serum of 53 subjects with PWS and 34 patients with non-syndromic obesity, utilizing a proximity extension assay with the Olink Target 96 neuro-exploratory and neurology panels. The ANOVA p-values were adjusted for multiple testing using the Benjamani–Hochberg method. Protein–protein interaction networks were generated in STRING V.12. Corrplots were calculated with R4.2.2 by using the Hmisc, Performance Analytics, and Corrplot packages Results: Our investigation explored the potential genetic underpinnings of the circulating protein signature observed in PWS, revealing intricate connections between genes in the PWS critical region and the identified circulating proteins associated with impaired oxytocin, NAD metabolism, and sex-related neuromuscular impairment involving, CD38, KYNU, NPM1, NMNAT1, WFIKKN1, and GDF-8/MSTN. The downregulation of CD38 in individuals with PWS (p < 0.01) indicates dysregulation of oxytocin release, implicating pathways associated with NAD metabolism in which KYNU and NMNAT1 are involved and significantly downregulated in PWS (p < 0.01 and p < 0.05, respectively). Sex-related differences in the circulatory levels of WFIKKN1 and GDF-8/MSTN (p < 0.05) were also observed. Conclusions: This study highlights potential circulating protein biomarkers associated with impaired oxytocin, NAD metabolism, and sex-related neuromuscular impairment in PWS individuals with potential clinical implications.

Targeting MCH Neuroendocrine Circuit in Lateral Hypothalamus to Protect Against Skeletal Senescence.

Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism and skeletal senescence is unelucidated. Here, a central neuroendocrine circuit is identified that directly controls osteogenesis. Using virus based tracing, this study is identified that melanin concentrating hormone (MCH) expressing neurons in the lateral hypothalamus (LH) are connected to the bone. Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis. Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs) and induces senescence. Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling, and activating MCHR1 by MCH agonists attenuate skeletal senescence in mice. By elucidating a brain-bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation and protect against skeletal senescence.

Effect of highly-active antiretroviral therapy on neuroendocrine regulation of immunogenesis in HIV-infected children

Comparative assay has been made against the parameters of the immune and endocrine systems in 84 HIV-infected children born from HIV-infected mothers. One group of analyzed children (36 patients) did not receive highly-active antiretroviral therapy. Another group (48 patients) received different variants of highly-active antiretroviral therapy. Children aged from 1 to 182 months were examined. Venous blood samples taken from young patients were used to determine leukocyte blood composition considering the relative (%) and absolute number of blood cell counts. Hormone concentration was determined concurrently. CD-molecule expression by mononuclear cells was registered using flow cytofluorimeter. Plasma viral load in HIV-infected children was quantitatively detected with RT-PCR. Statistically significant lowering in the levels of free thyroxin, cortisol and progesterone was observed in children against a background of highly-active antiretroviral therapy as compared to those without HAART use. Correlation assay between the hormone level and the immunological parameters in children not receiving the antiretroviral preparations revealed marked positive correlations among the somatotropic hormone level and CD3+, CD4+ and CD8+ absolute numbers. Similar positive correlation with absolute T-subset number was found against free T4. The progesterone level also positively correlated with relative CD3+ and CD8+ numbers and showed negative correlation with absolute CD4+ amount. There is another positive correlation with relative T-subset number against the dehydroepiandrosterone level in the group of children without antiretroviral preparation therapy. As for HIV-infected group of children, against a background of highly-active antiretroviral therapy, the results of correlation assay between the hormone concentrations and cell parameters were found to significantly vary. There were observed positive correlations between the levels of cortisol and CD3+ (%), cortisol and CD8+ (%), estradiol and CD4/CD8, progesterone and absolute CD8+ number. As with children not receiving the antiretroviral preparations marked positive relation was revealed between the concentration of free thyroxin and absolute values of CD4+. Negative correlations were recorded between the estradiol level and the relative CD3+ numbers. Against a background of applying the antiretroviral preparations the correlation assay conducted between the viral RNA concentration (lg of copy number of mRNA/ml) and analyzed endocrinological parameters was found to have marked positive correlation with HIV concentration demonstrated by estradiol and testosterone. During the antiretroviral therapy, however, the negative correlation between the thyrotropin level and lg concentration of viral RNA was observed. Analytical results of correlation among the viral RNA concentration (lg copy number of mRNA/ml) and analyzed immunological parameters in this group of children evidence for specific ‘normalization’ due to highly-active antiretroviral therapy as the only positive correlation with virus concentration was detected for CD4+T subsets. Therefore, the alteration in endocrine system state in children born from HIV-infected mothers could be of great significance while monitoring the systemic regulation of the immunogenesis.

The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity

ObjectiveObesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes. MethodsThe expression of the NPY/melanocortin receptors’ levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system. ResultsIn this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity. ConclusionsOur results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.

In Utero Exposure to Di-n-butyl Phthalate Causes Modulation in Neurotransmitter System of Wistar Rats: A Multigenerational Assessment.

Neuroendocrine regulation is disrupted by di-n-butyl phthalate (DBP) when exposure occurs during the critical periods of fetal development, which can lead to neurological disorders. To evaluate the toxic potential of DBP, it is necessary to conduct teratological studies, which could determine impacts on the development of the fetus. The present study was designed to understand the sequelae of neuroendocrine regulation in one-month-old pups when rats were exposed to DBP (F1-F3) in utero and during lactation. The rats received DBP (500mg/kg BW/day) dissolved in olive oil through oral gavage from gestation day 6 to postnatal day 30, while the control group received the olive oil (vehicle) during the same timeline. Following the exposure, thyroid profile and estradiol, which were measured at GD-19, exhibited a significant decrease (P < 0.05) in dams (F0-F2). The exposure resulted in developmental outcomes, including underdeveloped fetuses, and a notable number of resorptions in experimental rats. The one-month-old pups were assessed for serum thyroid profile and testosterone and neurotransmitters in discrete brain regions, cerebral cortex, cerebellum, and hippocampus for up to three generations. The levels of dopamine and cortisol showed a significant increase (P < 0.05), but serotonin levels decreased when examined in distinct brain regions of the experimental group as compared to the control. DBP, which is considered an endocrine disruptor, had the most impact on the third generation in this study, leading to a significant decrease in testosterone levels. In summary, in utero exposure to DBP impaired the neuroendocrine system and had an antiandrogenic effect in the three successive generations.

Detection of the effect of the KISS1 gene on reproductive parameters in Saanen goats

The KISS1 gene, which activates G protein-coupled receptor-54 (GPR54) and plays a crucial role in the neuroendocrine regulation of GnRH secretion, is known to encode a family of neuropeptides called kisspeptins. Therefore, the KISS1 gene is thought to be associated with sexual maturity, offspring development, and estrus. The g.2124T&amp;gt;A polymorphism of the KISS1 gene, is believed to affect the reproductive system, has been studied in Indonesian goat breeds, Damascus, Zarabi, Baladi, Gaddi, Kaligesing, Guanzong, Xinong Saanen and Boer goat breeds until now. These studies are generally related determining polymorphism frequencies or the effect of genotype on litter size. The study aims to determine the allele and genotype frequencies of the KISS1 gene g.2124T&amp;gt;A SNP by the PCR-RFLP method and define the relationship between the genotypic structures and reproductive parameters such as luteal growth, maximum corpus luteum diameter, and mating rate in Saanen goats (n=30). According to the results, the genotype frequencies in Saanen goats for the KISS1 gene g.2124T&amp;gt;A were 10.35%, 55.17%, and 34.48% for AA, TT and AT, respectively. Moreover, the genotypic structure did not have a statistically significant effect on the investigated fertility characteristics. The average values of expected heterozygosity (He), observed heterozygosity (Ho), the effective number of alleles (Ne), fixation index values (FIS), and the polymorphism information content (PIC) were 0.3996, 0.3448, 1.6655, 0.8629 and 0.855, respectively. The Hardy-Weinberg chi square (χ2) value was found to be 0.5435. In conclusion, it was found necessary to study the KISS1 - g.2124T&amp;gt;A polymorphism in larger herds with different gene pools as a reason for the existence of genotypic variation and the narrow population size.

Novel therapeutic opportunities of kisspeptin

Diseases associated with disorders of sexual development, the reproductive system, delayed of puberty onset are of high relevance. This negatively affect the health of young people, the demographic indicators, fertility and require a search for therapy. This review presents current data on the role of the kisspeptin ligand-receptor system KISS/KISS1R, the discovery of which was of revolutionary significance for deciphering the genesis of neuroendocrine regulation of the reproductive system.A review and analysis of clinical and experimental research from recent decades, aimed at studying kisspeptin and its agonists as a potential therapeutic approach. Data are presented on the positive effect of kisspeptin on the pulse secretion of GnRH and gonadotropins, which can be used in the treatment of hypogonadotropic hypogonadism, ovulation disorders and other diseases of the reproductive system. Outside the human hypothalamus, kisspeptin and its receptor are expressed in the brain in key limbic and paralimbic regions, and in peripheral tissues. We summarise data on the pharmacological use of kisspeptin in reproductive disorders and fertility treatment, as well as its putative utility in hypoactive sexual desire disorder, osteoporosis and non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated fatty liver disease.

The associations of spirituality and Hispanic ethnicity with neuroendocrine biomarkers among patients with colorectal cancer

ObjectiveDealing with cancer evokes not only physical and emotional distress, but may also promote resilience through spirituality. Patients with cancer are vulnerable to neuroendocrine dysregulation. This longitudinal observational study examined the degree to which spirituality was associated with neuroendocrine biomarkers and the moderating role of Hispanic ethnicity. MethodsParticipants were adults who were recently diagnosed with colorectal cancer (n = 81, 55 years old, 66% male, 63% Hispanic, 72% advanced cancer, 7 months post-diagnosis). The domains of spirituality (faith, meaning, and peace) and ethnicity (Hispanic vs. non-Hispanic) were self-reported. Cortisol and alpha amylase (sAA) were assayed from saliva samples collected at waking and bedtime on seven consecutive days. Mean levels at waking and bedtime, and diurnal slopes over seven days were calculated. Age and cancer stage were covariates. Results: Overall, patients reported moderate to high levels of spirituality. General linear modeling revealed that greater faith was associated with higher levels of sAA at waking and bedtime as well as more blunted diurnal pattern of sAA only among Hispanic patients (p ≤ .045). Greater peace was associated with steeper diurnal pattern of sAA, regardless of ethnicity (B = 0.021, p = .005). Meaning and cortisol were not significantly associated with study variables. ConclusionsFindings indicate that presence of peace facing a cancer diagnosis associated with neuroendocrine regulation, whereas drawing on one's faith, particularly among Hispanic patients, associated with neuroendocrine dysregulation during the first months after the diagnosis. Further investigations of psychobiobehavioral moderators and mediators for healthy neuroendocrine functioning among patients with cancer are warranted.

Norepinephrine Neurons in the Nucleus of the Solitary Tract Suppress Luteinizing Hormone Secretion in Female Mice.

Stress impairs fertility, at least in part, via inhibition of gonadotropin secretion. Luteinizing hormone (LH) is an important gonadotropin that is released in a pulsatile pattern in males and in females throughout the majority of the ovarian cycle. Several models of stress, including acute metabolic stress, suppress LH pulses via inhibition of neurons in the arcuate nucleus of the hypothalamus that coexpress kisspeptin, neurokinin B, and dynorphin (termed KNDy cells) which form the pulse generator. The mechanism for inhibition of KNDy neurons during stress, however, remains a significant outstanding question. Here, we investigated a population of catecholamine neurons in the nucleus of the solitary tract (NTS), marked by expression of the enzyme dopamine beta-hydroxylase (DBH), in female mice. First, we found that a subpopulation of DBH neurons in the NTS is activated (express c-Fos) during metabolic stress. Then, using chemogenetics, we determined that activation of these cells is sufficient to suppress LH pulses, augment corticosterone secretion, and induce sickness-like behavior. In subsequent studies, we identified evidence for suppression of KNDy cells (rather than downstream signaling pathways) and determined that the suppression of LH pulses was not dependent on the acute rise in glucocorticoids. Together these data support the hypothesis that DBH cells in the NTS are important for regulation of neuroendocrine and behavioral responses to stress.

P-708 melatonin alleviates circadian rhythm disruption-induced enhanced luteinizing hormone pulsatility and ovarian dysfunction in vivo and in vitro

Abstract Study question Is melatonin deficiency a reversible cause of abnormal pattern of luteinizing hormone (LH) pulsatility and ovarian dysfunction caused by circadian rhythm disruption (CRD)? Summary answer Melatonin could rescue the augmented LH pulsatility and reproductive abnormalities caused by CRD. What is known already Melatonin, mainly synthesized and released by pineal gland, engages in regulating circadian rhythms. When circadian rhythms are disrupted, the nocturnal productions of melatonin are suppressed. Evidence suggests that circadian rhythm disruption (CRD) is associated with reproductive dysfunctions, while melatonin plays a vital role for female reproduction as a free radical scavenger and a neuroendocrine regulator. The gonadotrophin-releasing hormone (GnRH) drives pulsatile luteinizing hormone (LH) secretion, which is also essential for fertility. Study design, size, duration We used 90 CBA/CaJ mice to establish the chronic jet-lag model in which mice were exposed to an 8 hr time shift every 3 days. After 8 weeks of jet-lag induction, some of the mice were given melatonin treatment for 4 weeks. Furthermore, we used a perfusion system in vitro to mimic the process of CRD-induce high-frequency GnRH pulses stimulation of LβT2 gonadotrope cells. Participants/materials, setting, methods Repetitive tail-tip blood collection was used to evaluate the pattern of LH pulsatility. Blood plasma samples were collected from 4 mice at 4-hour intervals to measure levels of melatonin. Follicular development was evaluated by ovarian histology. Reproductive hormones was detected by ELISA. Immunohistochemistry and western blot were used to detect the expression of melatonin receptor 1A (MT1). The LβT2 cells were exposed to pulsatile GnRH at high pulse frequencies to mimic augmented pulsatile GnRH stimulation. Main results and the role of chance CRD mice exhibited reproductive-endocrine dysfunction, including irregular estrous cycles, reduced number of corpus lutea (CL), and decreased levels of estradiol and progesterone. Additionally, CRD enhanced the frequency and amplitude of LH pulsatility and pituitary LH beta-subunit expression. Melatonin administration alleviated these CRD-induced reproductive abnormalities and reversed the augmented LH pulsatility. The expression of MT1 decreased in the anterior pituitaries of CRD mice but increased after melatonin treatment, indicating the essential role of MT1 in melatonin’s reversal of CRD-induced enhanced LH pulsatility. Limitations, reasons for caution Further research is needed to validate the applicability and safety of these findings in humans. Wider implications of the findings The results suggest that melatonin may be a beneficial option for patients with reproductive-endocrine abnormalities, particularly those with circadian rhythm disruption. Trial registration number 82101719

A complete study of neuroendocrine regulation of fish reproduction. 4. Migration impulse as a starting mechanism of spawning

The participation of the hypothalamo-hypophysial neurosecretory system (NS) in the initiation of anadromous fish spawning migration was established on the basis of ecological-histophysiological analysis the results of histomorphological, immunohistochemical and electron microscopic studies for the first time. Activation of the neurosecretory products synthesis in the neurosecretory cells perikaryons and their excretion into the cerebrospinal fluid of the III brain ventricle in anadromous migrants forms at the beginning of the river spawning migration, spring-spawning: Russian sturgeon, stellate sturgeon and autumn-spawning: pink salmon and chum salmon, was shown. Transport and mass accumulation of neurosecretory products in the neurohypophysis were discovered at the same time. It is concluded, that the NS impacts a complex synchronous effect, which consists: firstly, in the neurotropic effect of nonapeptide neurohormones (NPh) on behavioral centers, which causes a dominant state of CNS excitation corresponding to the “Migration impulse”; secondly, in the violation of the long-term adapted marine “Pastured” level of osmoregulation; and thirdly, in the cessation of the well-known antigonadotropic effect of NPh, which contributes the organism transition to the energyconsuming energy type of metabolism. A comparative analysis (cross-analysis) of our own and literature data confirms the commonality and points to the universality of this metabolic mechanism for different forms of migration in fish ontogeny, which allows us to consider it as the most important aromorphosis type of phylogenetic adaptations, aimed at the species biological progress achieving. In the subsequent navigational mechanisms of homing, widely covered in the world literature, the leading role is played by the luliberinergic centers of the hypothalamus. The ecological diversity of these population-level mechanisms and the presence of straing in fish allow us to consider them as specializations of microevolutionary origin. The most promising direction for the further neuroendocrinological research development seems to be the analysis of the mechanisms of imprinting in connection with the enhancement of growth and survival of juveniles in the critical salinity medium, and for the purpose of homing control (development of the commercial fish-return biotechnology management) — the mechanisms of interaction between the NS and the luliberinergic centers in the neuroendocrine complex of CNS.

Transcriptomic Responses and Larval-Stage Growth of Protandrous Yellowfin Seabream (Acanthopagrus Latus) to Different Polyethylene Microplastics Exposure.

Polyethylene microplastics (PE-MPs) were widespread in the marine environment; thus, their influences on marine hermaphroditic fish cannot be ignored. This study intends to evaluate the adverse biological effects of two different sources of PE, identified by Raman spectroscopy, on protandrous yellowfin seabream (Acanthopagrus latus) larvae. Growth retardation, brain lesions, head/body length ratio increase, and neuroendocrine system disorders were found, and growth and neuroendocrine regulation-related genes such as sstr2, ghrb, irs1, UGT2B15, UGT2C1, drd4a, esr2b, hsd3b7, and hsd17b2 were identified. PE microbeads (100 μm) showed more severe tissue damage on fish, while environmental PE fibers (500-2500 μm) showed more imperceptible adverse effects. There were 218 DEGs up-regulated and 147 DEGs down-regulated in the environmental PE group, while 1284 (up) and 1267 (down) DEGs were identified in the virgin PE group. PE-MP stress influenced physiological processes like growth and neuroendocrine regulation and cholesterol-steroid metabolism, and caused tissue damage in the fish larvae. The study highlights the effects of environmental PE exposure on hermaphroditic protandrous fish.

Identification of growth-associated miRNAs, circRNAs, and their corresponding regulatory networks in fast- and slow- growing families of Takifugu rubripes

Tiger puffer (Takifugu rubripes) is one of the most expensive farmed marine fish species in East Asia. Growth traits are important economic factors in cultured fish, miRNAs and circRNAs play important roles in growth and development. However, little is known of how miRNAs and circRNAs contribute to regulating fish growth through neuroendocrine regulation. To explore the role of miRNAs and circRNAs in regulating T. rubripes growth, RNA sequencing technology was used to sequence whole brain tissue transcriptomes from fast and slow-growing T. rubripes families. A total of 14 and 261 differentially expressed (DE) circRNAs and miRNAs were identified, respectively, in brain tissues. Among these, the expression levels of circCacna1c may maintain stable neuroendocrine environments by precisely regulating intracellular calcium (Ca2+) concentrations, thereby accelerating T. rubripes growth. Notably, genes including tgfb3, bmp2b, and bmp16 appeared to modulate T. rubripes development by coordinating neural activities during development via the Smad pathway. A miRNA-mRNA regulatory network was also identified that comprised 98 and 113 DE miRNAs and mRNAs, respectively. miR-124-4-3p and miR-124-4-5p of the miR-124 family were implicated in the regulation of neural development in T. rubripes by suppressing target genes like runx3, hoxb3a, mdfic, flt3, smo and syt10. In addition, 8 circRNA-miRNA-mRNA pathways were constructed including 2 circRNAs, 5 miRNAs, and 2 mRNAs. DE miRNAs and circRNAs identified here are primarily involved in nerve development and the maintenance of Ca2+ homeostasis in fast- and slow-growing T. rubripes. Overall, these results inform a better understanding of growth-related transcriptional dyanmics in T. rubripes brains, but also aid in the systematic selection and breeding of new varieties with higher qualities and yields.