Neuroendocrine Mechanisms Research Articles

Cocaine-Induced Time-Dependent Alterations in Cytochrome P450 and Liver Function

Cytochrome P450 is responsible for the metabolism of endogenous substrates, drugs and substances of abuse. The brain and nervous system regulate liver cytochrome P450 via neuroendocrine mechanisms, as shown in rodents. Cocaine exerts its addictive effects through the dopaminergic system, the functioning of which undergoes changes during its continuous use. Therefore, it can be hypothesized that the regulation of cytochrome P450 by cocaine may also alter during the addiction process, cessation and relapse. We analyzed preclinical studies on the mechanisms of the pharmacological action of cocaine, the role of the brain's dopaminergic system in the neuroendocrine regulation of cytochrome P450 and the in vitro and in vivo effects of cocaine on the cytochrome P450 expression/activity and hepatotoxicity. The results of passive cocaine administration indicate that cocaine affects liver cytochrome P450 enzymes (including those engaged in its own metabolism) via different mechanisms involving the expression of genes encoding cytochrome P450 enzymes and interaction with enzyme proteins. Thus, it may affect its own oxidative metabolism and the metabolism of endogenous substrates and other co-administered drugs and may lead to hepatotoxicity. Its effect depends on the specific cytochrome P450 enzyme affected, cocaine dosage, treatment duration and animal species. However, further complementary studies are needed to find out whether cocaine affects cytochrome P450 via the brain's dopaminergic system. The knowledge of cocaine's effect on cytochrome P450 function during the entire addiction process is still incomplete. There is a lack of information on the enzyme expression/activity in animals self-administering cocaine (addicted), in those withdrawn after cocaine self-administration, and during relapse in animals previously addicted; furthermore, there is no such information concerning humans. The subject of cytochrome P450 regulation by cocaine during the addiction process is an open issue, and addressing this topic may help in the treatment of drug abuse patients.

Nerve growth factor causes epinephrine release dysfunction by regulating phenotype alterations and the function of adrenal medullary chromaffin cells in mice with allergic rhinitis.

The presence of allergic rhinitis (AR) is an increased risk factor for the occurrence of bronchial asthma (BA). Nerve growth factor (NGF), in addition to its key role in the development and differentiation of neurons, may also be an important inflammatory factor in AR and BA. However, the pathogenesis of the progression of AR to BA remains to be elucidated. The present study aimed to investigate the ability of NGF to mediate nasobronchial interactions and explore possible underlying molecular mechanisms. In the present study, an AR mouse model was established and histology of nasal mucosa tissue injury was determined. The level of phenylethanolamine N‑methyl transferase in adrenal medulla was determined by immunofluorescence. Primary adrenal medullary chromaffin cells (AMCCs) were isolated and cultured from the adrenal medulla of mice. The expression levels of synaptophysin (SYP), STAT1, JAK1, p38 and ERK in NGF‑treated and untreated AMCCs were detected by reverse‑transcription‑quantitative PCR and western blotting. The epinephrine (EPI) and norepinephrine (NE) concentrations were measured by ELISA. It was found that the expression of SYP in AMCCs was enhanced in the presence of NGF, whereas, the concentration of EPI decreased significantly under the same conditions. Furthermore, NGF mediated the phenotypic and functional changes of AMCCs, resulting in decreased EPI secretion via JAK1/STAT1, p38 and ERK signaling. In conclusion, these findings could provide novel evidence for the role of NGF in regulating neuroendocrine mechanisms.

Emerging non-invasive therapeutic approaches targeting hypocholinergic neural systems in Parkinson's disease.

Emerging non-invasive therapeutic approaches targeting hypocholinergic neural systems in Parkinson's disease.

A Rare Case of Shared Delusion of Pregnancy in a Couple Undergoing Fertility Treatment

Pseudocyesis or phantom pregnancy is a false belief of being pregnant that is associated with objective signs and reported symptoms of pregnancy, which may include abdominal enlargement, reduced menstrual flow, amenorrhea, subjective sensation of fetal movement, nausea, breast engorgement and secretions, and labor. Though it is a very rare condition, it is often seen in women undergoing fertility treatment in developing countries. Isolated pseudocyesis in women and sometimes men have been reported before, but there are very few reports of shared delusions of pregnancy by a couple. No such report has ever been made before from Nepal. Therefore, this case report seeks to associate psychiatric/psychological, gynecological, and neuroendocrine mechanisms leading to the emergence of shared delusion of pregnancy (folie à deux) in a Nepali couple undergoing artificial reproductive techniques for the management of infertility. In this case, the couple firmly believed in their pregnancy against all medical evidence.

DIURNAL CORTISOL SECRETION AND SELF-REPORTED AND CAREGIVER-REPORTED QUALITY OF LIFE IN PEOPLE LIVING WITH DEMENTIA

Abstract Introduction People living with dementia (PLwD) report lower quality of life (QoL), compared to healthy older adults. The poorer QoL is not fully accounted for by the severity of dementia. Dementia is associated with prominent neuroendocrine changes, however, there is a lack of research examining whether biological factors are related to QoL in PLwD. This study examined relationships between cortisol, symptom severity, and QoL in PLwD. Methods A total of 143 participants aged 55-94 years (65.7% women) in the Healthy Patterns Study (NCT03682185) provided three saliva samples at wake-up (AM1), 30 minutes (AM2) after waking, and bedtime (PM) on two consecutive days. We derived cortisol awakening response (CAR), wake to bedtime cortisol slope, and diurnal mean cortisol secretion. Sociodemographic and severity of dementia were assessed by interviews and questionnaires. Self-reported and caregiver-reported QoL was measured using the Quality of Life in Alzheimer’s Disease (QoL-AD). Results Poorer QoL was associated with more severe dementia rating. Flattened cortisol slope was significantly correlated with overall poorer self-reported QoL (β=0.43, p=0.017), but not caregiver-reported QoL (p=0.12), after controlling for severity of dementia and demographic variables. We did not find a significant relationship between CAR and diurnal mean cortisol with QoL. Conclusions This study provides novel evidence linking neuroendocrine mechanisms to QoL in PLwD. The findings indicate that dysregulation of the hypothalamic-pituitary-adrenal axis is linked to poorer QoL, independently of the severity of dementia. Biopsychosocial approaches to QoL for PLwD may lead to a greater understanding of the underlying mechanisms.

Prior parental experience attenuates hormonal stress responses and alters hippocampal glucocorticoid receptors in biparental rock doves.

In the face of challenges, animals must balance investments in reproductive effort versus their own survival. Physiologically, this tradeoff may be mediated by glucocorticoid release by the hypothalamic-pituitary-adrenal (HPA) axis and prolactin release from the pituitary to maintain parental care. The degree to which animals react to and recover from stressors likely affects maintenance of parental behavior and ultimately, fitness. However, less is known about how gaining parental experience may alter hormonal stress responses and their underlying neuroendocrine mechanisms. To address this gap, we measured the corticosterone (CORT) and prolactin (PRL) stress response in both sexes of the biparental rock dove (Columba livia) that had never raised chicks versus birds that had fledged at least one chick. We measured both CORT and PRL at baseline and after an acute stressor (30 minutes restraint). We also measured negative feedback ability by administering dexamethasone, a synthetic glucocorticoid that suppresses CORT release, and measured CORT and PRL after 60 minutes. All hormones we measured when birds were not actively nesting to assess whether effects of parental experience extend beyond the breeding bout. Experienced birds had lower stress-induced and negative-feedback CORT, and higher stress-induced PRL than inexperienced birds. In a separate experiment, we measured glucocorticoid receptor subtype expression in the hippocampus, a key site of negative feedback regulation. Experienced birds expressed higher glucocorticoid receptors than inexperienced controls, which may mediate their ability to attenuate CORT release. Together, these results shed light on potential mechanisms by which gaining experience may improve parental performance and fitness.

Photoperiod alters testicular methyltransferase complex mRNA expression in Siberian hamsters

Exposure to long photoperiods stimulates, whereas exposure to short photoperiods transiently inhibit testicular function in Siberian hamsters via well-described neuroendocrine mechanisms. However, less is known about the intra-testicular regulation of these photoperiod-mediated changes. N6-methyladenosine (m6A) is one of the most common mRNA modifications in eukaryotes, with alterations in m6A mRNA methylation affecting testis function and fertility. We hypothesized that genes controlling m6A methylation such as methyltransferase-like-3 (Mettl3) and −14 (Mettl14) and Wilms’ tumor-1 associated protein (Wtap), part of an mRNA methylating methyl-transferase complex, or the fat-mass-and-obesity-associated (Fto) and the α-ketoglutarate-dependent dioxygenase alkB homolog-5 (Alkbh5) genes responsible for m6A demethylation, may be differentially regulated by photoperiod in the testis. Male hamsters were exposed to long (LD, control) photoperiod for 14-weeks, short (SD) photoperiod for 2, 5, 8, 11 and 14-weeks to induce regression, or SD for 14-weeks followed by transfer to LD for 1, 2, 4 or 8-weeks to induce recrudescence (post-transfer, PT). SD exposure significantly reduced body, testis, and epididymal masses compared to all other groups. Spermatogenic index, seminiferous tubule diameters and testosterone concentrations significantly decreased in SD as compared to LD, returning to levels no different than LD in post-transfer groups. SD exposure significantly decreased Wtap, Fto, Alkbh5, but increased Mettl14 mRNA expression as compared to LD, with values in PT groups restored to LD levels. Mettl3 mRNA expression did not change. These results suggest that testicular recovery induced by stimulatory photoperiod is relatively rapid, and that the methyltransferase complex may play a role during photostimulated testicular recrudescence.

Neuroendocrine mechanisms in oxaliplatin-induced hyperalgesic priming.

Stress plays a major role in the symptom burden of oncology patients and can exacerbate cancer chemotherapy-induced peripheral neuropathy (CIPN), a major adverse effect of many classes of chemotherapy. We explored the role of stress in the persistent phase of the pain induced by oxaliplatin. Oxaliplatin induced hyperalgesic priming, a model of the transition to chronic pain, as indicated by prolongation of hyperalgesia produced by prostaglandin E 2 , in male rats, which was markedly attenuated in adrenalectomized rats. A neonatal handling protocol that induces stress resilience in adult rats prevented oxaliplatin-induced hyperalgesic priming. To elucidate the role of the hypothalamic-pituitary-adrenal and sympathoadrenal neuroendocrine stress axes in oxaliplatin CIPN, we used intrathecally administered antisense oligodeoxynucleotides (ODNs) directed against mRNA for receptors mediating the effects of catecholamines and glucocorticoids, and their second messengers, to reduce their expression in nociceptors. Although oxaliplatin-induced hyperalgesic priming was attenuated by intrathecal administration of β 2 -adrenergic and glucocorticoid receptor antisense ODNs, oxaliplatin-induced hyperalgesia was only attenuated by β 2 -adrenergic receptor antisense. Administration of pertussis toxin, a nonselective inhibitor of Gα i/o proteins, attenuated hyperalgesic priming. Antisense ODNs for Gα i 1 and Gα o also attenuated hyperalgesic priming. Furthermore, antisense for protein kinase C epsilon, a second messenger involved in type I hyperalgesic priming, also attenuated oxaliplatin-induced hyperalgesic priming. Inhibitors of second messengers involved in the maintenance of type I (cordycepin) and type II (SSU6656 and U0126) hyperalgesic priming both attenuated hyperalgesic priming. These experiments support a role for neuroendocrine stress axes in hyperalgesic priming, in male rats with oxaliplatin CIPN.

Neuroendocrine Blockade of the Reproductive Axis in Female Athletes

This review aims at defining the neuroendocrine mechanisms underlying the sport-induced restrictions of the reproductive axis in female athletes. Episodic gonadotropin release was found to be compromised, presumably a result of impaired hypothalamic pulsatile GnRH release. Any deviation from optimal gonadotropin release may result in a suboptimal function of the ovaries, leading to disorders of the menstrual cycle and ovulation. A whole spectrum of menstrual dysfunctions ranging from ovulatory eumenorrhea to luteal phase defects and amenorrhea has been reported in sportive women. As essential neuroendocrine factors underlying these observations, activation of the adrenal axis and altered central nervous neurotransmitter activity have been identified to transfer metabolic, nutritional, and stress signals into the hypothalamic GnRH release. The degree by which the neuroendocrine axis governing reproduction is impaired critically depends on the intensity and duration of exercise and the state of training. Other decisive factors may be energy expenditure and availability, nutritional components, and the maturity of the hypothalamic-pituitary-ovarian (HPO) axis when sport activity was initiated. In conclusion, the gradual cessation of reproductive function observed in female athletes may be interpreted as an adaptive mechanism in response to physical and psychological endurance during sport. This sport-induced restriction of reproductive capacity may serve as protection (endogenous contraception) to preserve a woman’s health.

A tale of two hierarchies: Hormonal and behavioral factors underlying sex differences in social dominance in cooperative breeding callitrichids

Callitrichid primates are recognized for high levels of sociality in small groups, their great behavioral flexibility, and single-female dominant hierarchies. Previous work has highlighted that dominant, breeding callitrichids engage in behavioral and hormonal reproductive suppression of related and unrelated subordinates by both producing more offspring, having higher levels of ovulatory hormones, and accessing more sociosexual opportunities. This suppression constitutes a nexus of changes in pituitary responsiveness, ovarian cyclicity, sexual behavior, affiliation, and aggression. In this review, I will highlight important features that characterize callitrichid social hierarchies across broad social contexts. Dominant females sometimes exert reproductive suppression on subordinate nonbreeding females, but this suppression varies across callitrichids based on social stability and changes in group composition, particularly related to the number, experience, and age of nonbreeding subordinates. Meanwhile, dominant males may induce suppression of reproduction in subordinate males, but these effects occur by different behavioral and endocrine mechanisms and to a much lesser extent than their female counterparts; While dominant female callitrichids usually show higher levels of aggression relative to their male counterparts, callitrichids show a general absence of intersexual dominance, likely as an effort of maintaining a cohesive breeding pair within a stable social group and social cooperation. Future efforts are needed to identify precise neuroendocrine mechanisms underlying the presence of sex differences in callitrichid behavior separate from peripheral reproductive function. This is especially important with regard to parental experience, social relationships, development and aging, with larger implications toward understanding sex differences in overall health and wellbeing.

Socially Induced Infertility in Naked and Damaraland Mole-Rats: A Tale of Two Mechanisms of Social Suppression.

The naked mole-rat (Heterocephalus glaber) and the Damaraland mole-rat (Fukomys damarensis) possess extreme reproductive skew with a single reproductive female responsible for reproduction. In this review, we synthesize advances made into African mole-rat reproductive patterns and physiology within the context of the social control of reproduction. Non-reproductive female colony members have low concentrations of luteinising hormone (LH) and a reduced response of the pituitary to a challenge with gonadotropin releasing hormone (GnRH). If the reproductive female is removed from the colony, an increase in the basal plasma LH and increased pituitary response to a GnRH challenge arises in the non-reproductive females, suggesting the reproductive female controls reproduction. Non-reproductive male Damaraland mole-rats have basal LH concentrations and elevated LH concentrations in response to a GnRH challenge comparable to the breeding male, but in non-breeding male naked mole-rats, the basal LH concentrations are low and there is a muted response to a GnRH challenge. This renders these two species ideal models to investigate physiological, behavioural and neuroendocrine mechanisms regulating the hypothalamic-pituitary-gonadal axis. The recently discovered neuropeptides kisspeptin and RFamide-related peptide-3 are likely candidates to play an important role in the regulation of reproductive functions in the two mole-rat species.

Potential mechanisms of action and effectiveness of electroconvulsive therapy in the treatment of depressive disorders

The aim of this study is to prove the positive effect of electroconvulsive therapy on depressive disorders.
 Depression as a mental illness has not been fully studied in terms of its relationship in combination with electroconvulsive therapy. Nevertheless, despite many uncertainties, its positive effect on this type of treatment is indicated. Analysing a number of studies, electroconvulsive therapy is considered to be the most effective treatment for depression. As the research work shows, thanks to the use of electroconvulsive therapy in older people over 60 years of age, a positive effect on the patient's health can be observed in the entire study group.
 The mechanism of action of electroconvulsive therapy is multifaceted. There are several theories of how it works, affecting different areas of the individual's body. These include an anticonvulsant theory (GABAergic), effects on serotonergic and dopaminergic functions in the brain, effects on neurogenesis in the hippocampus and amygdala and neuropathicity, effects on gene transcription, an increase in the Narp protein with a presumed antidepressant effect, support for the neuroendocrine mechanism, as well as effects on inflammation (cytokines).

OR15-4 Heterogeneity of Clinical Presentation of Adolescent PCOS Is Attributable to Distinct Subtypes

Abstract Objective Adolescent polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome characterized by hyperandrogenism and irregular menses. Heterogeneous features of the syndrome include the presence/absence of obesity, degree of insulin resistance, and clinical and/or biochemical hyperandrogenism. In adult women with PCOS, discrete metabolic and reproductive subgroups can be identified. A recent study described distinct phenotypes using unsupervised hierarchical cluster analysis: a metabolic subgroup characterized by higher BMI, glucose, and insulin levels, and a reproductive subgroup demonstrating higher LH and SHBG levels. We hypothesized that non-obese and obese adolescent girls with PCOS would exhibit similar distinct phenotypes at the time of diagnosis. Methods Data were extracted from a multi-site PCOS registry including seven academic centers in the US with the following inclusion criteria: PCOS confirmed per 2018 international guidelines, diagnosis before age 18 years, and at least one follow-up visit. Data collected included demographics, medical and family history, physical characteristics including hirsutism, acanthosis nigricans, and laboratory measures such as HbA1c, ALT, lipid profiles and reproductive hormones (androgens, LH, FSH, SHBG). Hormone levels were normalized to the upper limit provided by the measuring laboratory. Patients were divided by obesity status, defined as obese (OB) with BMI ≥ 95th percentile for age and sex and non-obese (NO) < 85th percentile for age and sex. Differences in continuous variables were assessed with unpaired t-tests using GraphPad Prism. Results Complete diagnostic data from 390 patients from 7 different sites were included for analysis, with 284 OB (Age 15.3±1.5 years, BMI 36.1±5.6 kg/m2) and 68 NO (Age 15.8±1.3 years, BMI 22.6±3.4 kg/m2). OB presented with more severe acanthosis (p<0.0001) and higher HbA1c (OB 5.5±0.5, NO 5.2±0.3; %, p<0.0001), ALT (OB 35±30, NO 22±17; IU/L, p=0.0006), and triglycerides (OB 145±90, NO 110,±88; mg/dL, p=0.002). OB also presented with higher free testosterone (OB 219±188% vs NO 158±125% above upper limit of normal; p=0.003), while NO presented with higher total testosterone (OB 121±68%, NO 152±88% above upper limit of normal; p=0.003), androstenedione (OB 87±37%, NO 125±62 above upper limit of normal; p=0.002), and LH (OB 9.7±4.9, NO 15.2±10.4; mIU/mL, p=0.0001). No differences in Ferriman Gallwey score or number of menses in the 6 months prior to diagnosis were detected. Conclusions Metabolic and reproductive phenotypes differed in OB and NO adolescent girls at the time of PCOS diagnosis. The reproductive phenotype in NO was characterized by increased LH, total testosterone and androstenedione levels. In contrast, OB girls had a phenotype characterized by insulin resistance-driven hyperandrogenemia established by lower SHBG and higher free testosterone levels. Our data are consistent with findings reported for adult women with two divergent phenotypes: an insulin resistance-driven metabolic subtype and a primarily reproductive subtype, potentially driven by neuroendocrine mechanisms. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

Parameters of Iron Metabolism in Patients with Iron Deficiency Anemia and Erosive Lesions of the Gastroduodenal Zone

The most common disease in the world is erosive-ulcerative lesions of the gastroduodenal zone (EULGZ). These are chronic polyetiological, recurrent diseases with disruption of the neuro-endocrine and humoral mechanisms that regulate the secretory-trophic process in the gastroduodenal zone with the development of ulcers. In this disease, ulcers have different localization and clinical course, significantly reduce the quality of life, affect work capacity and personal life. Lack of timely diagnosis and treatment can have adverse consequences. The objective: to analyse the characteristics of clinical and metabolic disorders in iron deficiency anemia (IDA) and its combination with EULGZ in order to develop the methods for assessing the disease severity, optimizing diagnostics and treatment tactics. Materials and methods. The observation group included 26 patients (15 men and 11 women) with iron-deficiency anemia (IDA) on background of EULGZ with localization of ulcerative defects of the mucous membrane in the stomach or duodenal bulb. The diagnosis of IDA was verified on the basis of changes in the basic characteristics of clinical manifestations (signs of anemic hypoxia and sideropenic syndrome), specific changes in peripheral blood and indicators of iron metabolism. Patients with IDA and EULGZ, were examined by endoscopic methods, underwent ultrasound and, if necessary, radiological examination. The control group included 35 primary donors (16 women and 19 men), who underwent two laboratory tests for hepatitis B and C, as well as HIV infection/AIDS. All examined donors underwent a comprehensive examination of peripheral blood and determined biochemical indicators. The indicators of iron metabolism were determined in all participants: iron content in the blood serum (IS), total iron-binding capacity of the blood serum (TIBS). The index of unsaturated iron-binding capacity of blood serum was calculated as the difference between TIBS and IS. The coefficient of transferrin saturation with iron was determined as the ratio of the content of IS to TIBS. The content of transferrin was determined according to the TIBS indicator, ferritin – by the radiometric method. Results. Peripheral blood indicators in primary donors and morphometric changes in peripheral blood in patients with IDA were analyzed. The results of investigations of the indicators of iron exchange in blood serum are presented: iron concentration, total iron-binding capacity of serum and the degree of saturation of serum with iron. It was found that male donors have significantly higher levels of iron and ferritin in blood serum compared to female donors. The dynamic of changes in peripheral blood parameters in patients with IDA caused by long-term blood loss due to EULGZ during the treatment process is shown. Treatment of the EULGZ led to the significant changes of such indicators as the number of erythrocytes, hemoglobin concentration, erythrocyte indices towards normalization. The normalization of the reticulocyte count was observed on the 90th day of treatment. The detected changes in the number of platelets in patients with IDA due to EULGZ were observed in the absence of active bleeding from the digestive tract. Conclusions. As a result of the progression of IDA due to the erosive-ulcerative lesions of the gastroduodenal zone, the imbalance of iron metabolism deepens, serious disorders of iron metabolism develop, especially in the content of plasma ferritin. Patients with IDA caused by long-term blood loss as a result of EULGZ, should be prescribed a drug for oral use containing ferrous sulfate with a mucosa-protective effect at a dose of 2 mg/kg per day, followed by a decreased dose after normalization of the serum ferritin level.

Insights into the constellating drivers of satiety impacting dietary patterns and lifestyle.

Food intake and body weight regulation are of special interest for meeting today's lifestyle essential requirements. Since balanced energy intake and expenditure are crucial for healthy living, high levels of energy intake are associated with obesity. Hence, regulation of energy intake occurs through short- and long-term signals as complex central and peripheral physiological signals control food intake. This work aims to explore and compile the main factors influencing satiating efficiency of foods by updating recent knowledge to point out new perspectives on the potential drivers of satiety interfering with food intake regulation. Human internal factors such as genetics, gender, age, nutritional status, gastrointestinal satiety signals, gut enzymes, gastric emptying rate, gut microbiota, individual behavioral response to foods, sleep and circadian rhythms are likely to be important in determining satiety. Besides, the external factors (environmental and behavioral) impacting satiety efficiency are highlighted. Based on mechanisms related to food consumption and dietary patterns several physical, physiological, and psychological factors affect satiety or satiation. A complex network of endocrine and neuroendocrine mechanisms controls the satiety pathways. In response to food intake and other behavioral cues, gut signals enable endocrine systems to target the brain. Intestinal and gastric signals interact with neural pathways in the central nervous system to halt eating or induce satiety. Moreover, complex food composition and structures result in considerable variation in satiety responses for different food groups. A better understanding of foods and factors impacting the efficiency of satiety could be helpful in making smart food choices and dietary recommendations for a healthy lifestyle based on updated scientific evidence.

Sex-specific endocrine regulation of seasonal aggression in Siberian hamsters.

Coordinating physiological and behavioural processes across the annual cycle is essential in enabling individuals to maximize fitness. While the mechanisms underlying seasonal reproduction and its associated behaviours are well characterized, fewer studies have examined the hormonal basis of non-reproductive social behaviours (e.g. aggression) on a seasonal time scale. Our previous work suggests that the pineal hormone melatonin facilitates a 'seasonal switch' in neuroendocrine regulation of aggression in male and female Siberian hamsters (Phodopus sungorus), specifically by acting on the adrenal glands to increase the production of the androgen dehydroepiandrosterone (DHEA) during the short-day (SD) photoperiods of the non-breeding season. Here, we provide evidence that the activity of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD), a key enzyme within the steroidogenic pathway that mediates DHEA synthesis and metabolism, varies in a sex-specific and melatonin-dependent manner. Although both male and female hamsters displayed increased aggression in response to SDs and SD-like melatonin, only males showed an increase in adrenal 3β-HSD activity. Conversely, SD and melatonin-treated females exhibited reductions in both adrenal and neural 3β-HSD activity. Collectively, these results suggest a potential role for 3β-HSD in modulating non-breeding aggression and, more broadly, demonstrate how distinct neuroendocrine mechanisms may underlie the same behavioural phenotype in males and females.

GLP-1 attenuates intestinal fat absorption and chylomicron production via vagal afferent nerves originating in the portal vein

Background/ObjectiveGLP-1R agonists have been shown to reduce fasting and postprandial plasma lipids, both of which are independent risk factors for the development of cardiovascular disease. However, how endogenous GLP-1 – which is rapidly degraded – modulates intestinal and hepatic lipid metabolism is less clear. A vagal gut-brain-axis originating in the portal vein has been proposed as a possible mechanism for GLP-1’s anti-lipemic effects. Here we sought to examine the relationship between vagal GLP-1 signalling and intestinal lipid absorption and lipoprotein production. MethodsSyrian golden hamsters or C57BL/6 mice received portal vein injections of GLP-1(7-36), and postprandial and fasting plasma TG, TRL TG, or VLDL TG were examined. These experiments were repeated during sympathetic blockade, and under a variety of pharmacological or surgical deafferentation techniques. In addition, hamsters received nodose ganglia injections of a GLP-1R agonist or antagonist to further probe the vagal pathway. Peripheral studies were repeated in a novel GLP-1R KO hamster model and in our diet-induced hamster models of insulin resistance. ResultsGLP-1(7-36) site-specifically reduced postprandial and fasting plasma lipids in both hamsters and mice. These inhibitory effects of GLP-1 were investigated via pharmacological and surgical denervation experiments and found to be dependent on intact afferent vagal signalling cascades and efferent changes in sympathetic tone. Furthermore, GLP-1R agonism in the nodose ganglia resulted in markedly reduced postprandial plasma TG and TRL TG, and fasting VLDL TG and this nodose GLP-1R activity was essential for portal GLP-1s effect. Notably, portal and nodose ganglia GLP-1 effects were lost in GLP-1R KO hamsters and following diet-induced insulin resistance. ConclusionOur data demonstrates for the first time that portal GLP-1 modulates postprandial and fasting lipids via a complex vagal gut–brain–liver axis. Importantly, loss or interference with this signalling axis via surgical, pharmacological, or dietary intervention resulted in the loss of portal GLP-1s anti-lipemic effects. This supports emerging evidence that native GLP-1 works primarily through a vagal neuroendocrine mechanism.

Circadian clock and temporal meal pattern.

The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic consequences. Time-restricted feeding (TRF), with all calories consumed within less than 12-h per day, can improve metabolism and extend lifespan. A major component of TRF in humans is caloric restriction, which contributes significantly to the beneficial effects of TRF in humans. By comparison, TRF effects in rodents can be independent of caloric restriction and show day/night phase specificity. TRF could alleviate metabolic abnormalities due to circadian disruption, but its effects appear independent of the circadian clock in rodents. Understanding neuroendocrine mechanisms underlying clock-mediated metabolic regulation will shed light on the metabolic effects of temporal meal patterns.

Neuroendocrine regulation of female aggression.

Classically the neurobiology of aggression has been studied exclusively in males. Thus, females have been considered mildly aggressive except during lactation. Interestingly, recent studies in rodents and humans have revealed that non-lactating females can show exacerbated and pathological aggression similarly to males. This review provides an overview of recent findings on the neuroendocrine mechanisms regulating aggressive behavior in females. In particular, the focus will be on novel rodent models of exaggerated aggression established in non-lactating females. Among the neuromodulatory systems influencing female aggression, special attention has been given to sex-steroids and sex-steroid-sensitive neuronal populations (i.e., the core nuclei of the neural pathway of aggression) as well as to the neuropeptides oxytocin and vasopressin which are major players in the regulation of social behaviors.

Traditional Chinese medicine mediated tumor suppression via regulating psychological factors

Chronic psychological stress causes physiological stress and leads to disturbance in the body's internal environment. There is growing evidence that stress can promote cancer biological processes, including proliferation, genomic instability, angiogenesis, metastasis, immune evasion, and metabolic disorders, through neuroendocrine mechanisms, immune and inflammatory responses, and epigenetic alterations, and may even impact tumor therapy. In addition, as the tumor development process advances, the body also promotes depressive and anxiety-like behaviors through one or more of these mechanisms, generating a vicious cycle that contributes to the tumor's poor prognosis. However, psychosomatic behavioral interventions (PBI) and Chinese medicine can also effectively mitigate the effects of stress in cancer patients. In this review, we will explore the potential pathways of stress-tumor interactions.