Neuroendocrine System Research Articles

Sensory Nutrition and Bitterness and Astringency of Polyphenols.

Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential.

No evidence for relationship between paternal post-partum depressive symptoms and testosterone or cortisol in first-time fathers.

Male life history strategies are regulated by the neuroendocrine system. Testosterone (T) and cortisol regulate male behaviors including parenting and facilitate managing tradeoffs at key transitions in development such as first-time fatherhood. Both hormones demonstrate marked fluctuations in the postnatal period, and this presents an opportunity to investigate the role of T and cortisol in postpartum depressive symptoms-comparably less studied in fathers than in mothers in the evolutionary literature. Prior work on depressive symptoms has yet to integrate insights from the "dual hormone hypothesis (DHH)" which has focused on how T and cortisol interact to jointly regulate traits associated with dominance and status-seeking (i.e., mating effort) but has yet to be included in models of parenting effort. In this research, we use secondary data to investigate the relationship between DHH and traits ostensibly opposed to status seeking (i.e., depressive symptoms). First-time fathers (n = 193) provided morning saliva samples 10 months following parturition and reported on the presence of depressive symptoms (BDI-II). Responses were decomposed into three factors: cognitive, affective, and somatic. Using hybrid latent variable structural equation modeling, we did not find evidence that T predicted variability in cognitive, affective, or somatic depressive symptom factors. We found a null effect for cortisol as well. Finally, we could not find evidence that the DHH variable (T × cortisol interaction) predicted any variability in cognitive, affective, or somatic depressive symptoms. While we did not find evidence to support our hypotheses using a secondary data set, this study contributes to research on the neuroendocrinology of depression in fathers. Discussion focuses on the limitations of sample demographics, timing of saliva and self-report collection, and the lack of extant theory specific to paternal postpartum depression.

Cancer type and histology influence cutaneous immunotherapy toxicities: a multi-institutional cohort study.

Cutaneous immune-related adverse events (cirAEs) are the most common toxicities to occur in the setting of immune checkpoint inhibitor (ICI) therapy. Identifying patients who are at increased risk of developing cirAEs may improve quality of life and outcomes. To investigate the influence of cancer type and histology on the development of cirAEs in the setting of ICI therapy and survival outcomes. This retrospective cohort study included patients recruited between 1 December 2011 and 30 October 2020. They received ICI from 2011 to 2020 with follow-up of outcomes through October 2021. We identified 3668 recipients of ICI therapy who were seen at Massachusetts General Brigham and Dana-Farber. Of these, 669 developed cirAEs. Records that were incomplete or categories of insufficient sample size were excluded from the study cohort. Multivariate Cox proportional hazards models were used to investigate the impact of cancer organ system and histology on cirAE development, after adjusting for demographics, Charlson Comorbidity Index, ICI type, cancer stage at ICI initiation, and year of ICI initiation. Time-varying Cox proportional hazards modelling was used to examine the impact of cirAE development on mortality. Compared with other nonepithelial cancers (neuroendocrine, leukaemia, lymphoma, myeloma, sarcoma and central nervous system malignancies), cutaneous squamous cell carcinoma [cSCC; hazard ratio (HR) 3.57, P < 0.001], melanoma (HR 2.09, P < 0.001), head and neck adenocarcinoma (HR 2.13, P = 0.009), genitourinary transitional cell carcinoma (HR 2.15, P < 0.001) and genitourinary adenocarcinoma (HR 1.53, P = 0.037) were at significantly higher risk of cirAEs in multivariate analyses. The increased risk of cirAEs translated into an adjusted survival benefit for melanoma (HR 0.37, P < 0.001) and cSCC (HR 0.51, P = 0.011). The highest rate of cirAEs and subsequent survival benefits were observed in cutaneous malignancies treated with ICI therapies. This study improves our understanding of patients who are at highest risk of developing cirAEs and would, therefore, benefit from appropriate counselling and closer monitoring by their oncologists and dermatologists throughout their ICI therapy. Limitations include its retrospective nature and cohort from one geography.

Urban environment influences on stress, autonomic reactivity and circadian rhythm: protocol for an ambulatory study of mental health and sleep.

Converging evidence suggests that urban living is associated with an increased likelihood of developing mental health and sleep problems. Although these aspects have been investigated in separate streams of research, stress, autonomic reactivity and circadian misalignment can be hypothesized to play a prominent role in the causal pathways underlining the complex relationship between the urban environment and these two health dimensions. This study aims at quantifying the momentary impact of environmental stressors on increased autonomic reactivity and circadian rhythm, and thereby on mood and anxiety symptoms and sleep quality in the context of everyday urban living. The present article reports the protocol for a feasibility study that aims at assessing the daily environmental and mobility exposures of 40 participants from the urban area of Jerusalem over 7 days. Every participant will carry a set of wearable sensors while being tracked through space and time with GPS receivers. Skin conductance and heart rate variability will be tracked to monitor participants' stress responses and autonomic reactivity, whereas electroencephalographic signal will be used for sleep quality tracking. Light exposure, actigraphy and skin temperature will be used for ambulatory circadian monitoring. Geographically explicit ecological momentary assessment (GEMA) will be used to assess participants' perception of the environment, mood and anxiety symptoms, sleep quality and vitality. For each outcome variable (sleep quality and mental health), hierarchical mixed models including random effects at the individual level will be used. In a separate analysis, to control for potential unobserved individual-level confounders, a fixed effect at the individual level will be specified for case-crossover analyses (comparing each participant to oneself). Recent developments in wearable sensing methods, as employed in our study or with even more advanced methods reviewed in the Discussion, make it possible to gather information on the functioning of neuro-endocrine and circadian systems in a real-world context as a way to investigate the complex interactions between environmental exposures, behavior and health. Our work aims to provide evidence on the health effects of urban stressors and circadian disruptors to inspire potential interventions, municipal policies and urban planning schemes aimed at addressing those factors.

Low-frequency noise impairs righting reflex behavior by disrupting central nervous system in the sea slug Onchidium reevesii

Anthropogenic noise has significantly increased due to human activities, posing a threat to the health and survival of marine organisms. However, current studies have often emphasized its effects on the physiological aspects of marine organisms, while ignored the relationship between the neuroendocrine system and behavior. This study aimed to evaluate the righting behavior and relevant physiological functions of the central nervous system (CNS) in sea slug (Onchidium reevesii) exposed to low-frequency noise and subsequent noise removal. The duration of the sea slugs' righting reflex increased with longer noise exposure time. The degree of neuronal cell damage and apoptosis were significantly increased and relevant gene expressions were affected (Glu, AChE, FMRFamide and CaMKII) (P < 0.05). After the removal of noise, the righting reflex speed gradually recovered, and the degree of neuronal cell damage, apoptosis and the expression levels of genes continued to decrease. Pearson correlation analysis showed that the righting time was positively correlated with CNS tissue and DNA damage, apoptosis rate, and negatively correlated with the expression levels of genes. Therefore, low-frequency noise exposure causes damage to the CNS of sea slugs, subsequently impairing their normal behavior. Sea slugs exhibited partial recovery within 384 h after removing noise. These findings provide valuable insights into the effects of low-frequency noise on the CNS and behavior of marine invertebrates.

Evolutionary conserved peptide and glycoprotein hormone-like neuroendocrine systems in C. elegans

Peptides and protein hormones form the largest group of secreted signals that mediate intercellular communication and are central regulators of physiology and behavior in all animals. Phylogenetic analyses and biochemical identifications of peptide-receptor systems reveal a broad evolutionary conservation of these signaling systems at the molecular level. Substantial progress has been made in recent years on characterizing the physiological and putative ancestral roles of many peptide systems through comparative studies in invertebrate models. Several peptides and protein hormones are not only molecularly conserved but also have conserved roles across animal phyla. Here, we focus on functional insights gained in the nematode Caenorhabditis elegans that, with its compact and well-described nervous system, provides a powerful model to dissect neuroendocrine signaling networks involved in the control of physiology and behavior. We summarize recent discoveries on the evolutionary conservation and knowledge on the functions of peptide and protein hormone systems in C. elegans.

Association of early life adversity with cardiovascular disease and its potential mechanisms: a narrative review.

Strong epidemiological evidence has shown that early life adversity (ELA) has a profound negative impact on health in adulthood, including an increased risk of cardiovascular disease, the leading cause of death worldwide. Here, we review cohort studies on the effects of ELA on cardiovascular outcomes and the possible underlying mechanisms. In addition, we summarize relevant studies in rodent models of ELA. This review reveals that the prevalence of ELA varies between regions, time periods, and sexes. ELA increases cardiovascular health risk behaviors, susceptibility to mental illnesses, and neuroendocrine and immune system dysfunction in humans. Rodent models of ELA have been developed and show similar cardiovascular outcomes to those in humans but cannot fully replicate all ELA subtypes. Therefore, combining cohort and rodent studies to further investigate the mechanisms underlying the association between ELA and cardiovascular diseases may be a feasible future research strategy.

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells-In Vitro Studies on Melanocytes and Fibroblasts.

Hypertension is known to be a multifactorial disease associated with abnormalities in neuroendocrine, metabolic, and hemodynamic systems. Poorly controlled hypertension causes more than one in eight premature deaths worldwide. Hydrochlorothiazide (HCT) and furosemide (FUR), being first-line drugs in the treatment of hypertension, are among others the most frequently prescribed drugs in the world. Currently, many pharmacoepidemiological data associate the use of these diuretics with an increased risk of adverse phototoxic reactions that may induce the development of melanoma and non-melanoma skin cancers. In this study, the cytotoxic and phototoxic potential of HCT and FUR against skin cells varied by melanin pigment content was assessed for the first time. The results showed that both drugs reduced the number of metabolically active normal skin cells in a dose-dependent manner. UVA irradiation significantly increased the cytotoxicity of HCT towards fibroblasts by approximately 40% and melanocytes by almost 20% compared to unirradiated cells. In the case of skin cells exposed to FUR and UVA radiation, an increase in cytotoxicity by approximately 30% for fibroblasts and 10% for melanocytes was observed. Simultaneous exposure of melanocytes and fibroblasts to HCT or FUR and UVAR caused a decrease in cell viability, and number, which was confirmed by microscopic assessment of morphology. The phototoxic effect of HCT and FUR was associated with the disturbance of redox homeostasis confirming the oxidative stress as a mechanism of phototoxic reaction. UVA-irradiated drugs increased the generation of ROS by 10-150%, and oxidized intracellular thiols. A reduction in mitochondrial potential of almost 80% in melanocytes exposed to HCT and UVAR and 60% in fibroblasts was found due to oxidative stress occurrence. In addition, HCT and FUR have been shown to disrupt the cell cycle of normal skin cells. Finally, it can be concluded that HCT is the drug with a stronger phototoxic effect, and fibroblasts turn out to be more sensitive cells to the phototoxic effect of tested drugs.

Biomarkers of Brain Ischemia (Review)

Introduction. Strokes remain the second leading cause of death and the third leading cause of disability. Additional serum biomarker testing should be used to better diagnose transient ischemic attack (TIA), but most neurospecific biomarkers have low prognostic specificity and sensitivity. Timely identification of TIA and differential diagnosis of stroke in the first hour will ensure a shorter period of patient recovery and reduce the risk of mortality and disability. Serum biomarker studies should be included to overcome the difficulty of diagnosing TIA.Text. Neurospecific biomarkers such as S100B, GFAP, and NSE are used to diagnose acute ischemic damage to glial cells and neurons. S100B and GFAP are detected in astrocytes and NSE in neurons and cells of the neuroendocrine system. Elevated serum concentrations of these biomarkers are associated with various pathological conditions such as strokes and brain injuries and other central nervous system (CNS) lesions. Dynamic monitoring of biomarker concentrations makes it possible to evaluate the efficacy of the ongoing therapy and to identify predictors of patient deterioration for prompt correction of therapeutic procedures. To create a diagnostic panel it is necessary to study metabolic processes in ischemic tissue, taking into account concomitant diagnoses and results of neuroimaging, and to use breakthrough advances in machine learning and big data.Conclusion. The review showed that none of the assessed biomarkers can be recommended for the diagnosis of cerebral circulation disorders, but the combination of several neurospecific biomarkers can significantly improve diagnostic efficiency and find application in the differential diagnosis of stroke, intracranial hematoma, and other brain lesions for the purpose of early pharmacotherapy of CNS lesions and as surrogate endpoints during clinical trials.

Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis.

Type 2 diabetes mellitus (T2DM) has become one of the most serious public healthcare challenges, contributing to increased mortality and disability. In the past decades, significant progress has been made in understanding the pathogenesis of T2DM. Mounting evidence suggested that gut microbiota (GM) plays a significant role in the development of T2DM. Communication between the GM and the brain is a complex bidirectional connection, known as the "gut-brain axis," via the nervous, neuroendocrine, and immune systems. Gut-brain axis has an essential impact on various physiological processes, including glucose metabolism, food intake, gut motility, etc. In this review, we provide an outline of the gut-brain axis. We also highlight how the dysbiosis of the gut-brain axis affects glucose homeostasis and even results in T2DM.

Chronic Administration of Lisdexamfetamine Induces Apoptosis and Inflammation and Reduces Sperm Quality in Adult Male Rats.

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.

Thyroid gland: a rare site of metastasis.

Despite its rich vascularity, metastasis (MTS) to the thyroid tissue is unusual, ranging from 1 to 3%. This entity is not usually considered as differential diagnosis and is not included in the upfront approach in patients with thyroid nodules. Once diagnosed, treatment is controversial. The aim of this study was to evaluate diagnosis, treatment, and outcome at the end of follow-up in patients with a diagnosis of MTS to the thyroid. A retrospective multicenter study was designed from 1985 to 2022; 29 patients with MTS to the thyroid gland were included in the analysis. Clinical presentation included the presence of a nodular goiter (65.5%), compression symptoms (17.2%), diffuse goiter (10.3%), and suspicious lymph nodes in the neck (7%). Primary tumor sites were: kidney (44.8%), breast (24.1%), lung (13.8%), neuroendocrine system (6.9%), colon (3.4%), cervix (3.4%), and ovary (3.4%). In 18/23 patients, suspicious ultrasound criteria for malignancy were described. Preoperative diagnosis was made in 23/27 patients by FNA and confirmed in 18 cases by immunohistochemistry. Seventeen patients underwent surgery. At the end of the follow-up, 19 patients had died of oncological disease, and six were alive (2/6 disease-free with isolated intrathyroidal MTS). Renal carcinoma was the tumor that most frequently metastasized to the thyroid gland. Immunodiagnosis was a very useful tool for etiological confirmation. Patients with MTS to the thyroid gland as a unique site had a more favorable course compared to patients with multiple metastatic sites. Finally, outcomes and prognosis essentially depended on the biology of the primary tumor.

Pathophysiological Relationships of Neuroendocrine Immune Systems in Thyroid Diseases

Pathophysiological relationships of neuroendocrine immune systems in diseases of the thyroid gland. Signs of damage to the nervous system occupy a prominent place in the clinical manifestations of thyroid diseases. Sometimes they come to the fore, significantly complicating the diagnosis of the disease. They especially often experience asthenic syndrome, which consists of mental and physical asthenia, autonomic disorders, and sleep disturbances. Sometimes somatovegetative disorders predominate in these patients: palpitations, heart pain, shortness of breath, sweating, chills. It is well known that depression negatively affects general and somatic status. A syndrome of secondary immunological deficiency is formed. The pathogenetic basis for the mutual conditionality of these conditions are the mechanisms of neuroendocrine-immune interaction, which form a functional system consisting of a physiological and pathological basis. Clinical signs of the disease, the content of thyroid hormones, immune status, determination of autonomic tone, autonomic reactivity and autonomic support of activity were used. 75 patients were examined, and it was found that the disturbance of the neuroendocrine immune system depended on the functional activity of the thyroid gland.

Biomarkers for Depression: A Detailed View

A plethora of research has implicated hundreds of putative biomarkers for depression but has not yet fully elucidated their roles in depressive illness or established what is abnormal in which patients and how biologic information can be used to enhance diagnosis, treatment, and prognosis. This lack of progress is partially due to the nature and heterogeneity of depression, in conjunction with methodological heterogeneity within the research literature and the large array of biomarkers with potential, the expression of which often varies according to many factors. We review the available literature, which indicates that markers involved in inflammatory, neurotrophic, and metabolic processes, as well as neurotransmitter and neuroendocrine system components, represent highly promising candidates. These may be measured through genetic and epigenetic, transcriptomic and proteomic, metabolomic, and neuroimaging assessments. The use of novel approaches and systematic research programs is now required to determine whether, and which, biomarkers can be used to predict response to treatment, stratify patients to specific treatments, and develop targets for new interventions. We conclude that there is much promise for reducing the burden of depression through further developing and expanding these research avenues.

Autoimmune demyelination alters hypothalamic transcriptome and endocrine function

The hypothalamus is a brain structure that is deputed to maintain organism homeostasis by regulating autonomic function and hormonal production as part of the neuroendocrine system. Dysfunction in hypothalamic activity results in behavioral alterations, depression, metabolic syndromes, fatigue, and infertility. Remarkably, many of these symptoms are associated with multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system (CNS) characterized by focal demyelination, immune cell infiltration into the brain parenchyma, and neurodegeneration. Furthermore, altered hormonal levels have been documented in MS patients, suggesting the putative involvement of hypothalamic deficits in MS clinical manifestations. Yet, a systematic analysis of hypothalamic function in response to neuroinflammatory stress is still lacking. To fill this gap, here we performed a longitudinal profiling of the hypothalamic transcriptome upon experimental autoimmune encephalomyelitis (EAE)—a murine disease model recapitulating key MS phenotypes at both histopathological and molecular levels. We show that changes in gene expression connected with an anti-inflammatory response start already at pre-onset and persist along EAE progression. Altered levels of hypothalamic neuropeptides were also detected, which possibly underlie homeostatic responses to stress and aberrant feeding behaviors. Last, a thorough investigation of the principal endocrine glands highlighted defects in the main steroidogenic pathways upon disease. Collectively, our findings corroborate the central role of hypothalamic dysfunction in CNS autoimmunity.

Behavior and physiology in female Cricetulus barabensis are associated with the expression of circadian genes.

The circadian clock regulates the behavior, physiology, and metabolism of mammals, and these characteristics, such as sleep-wake cycles, exercise capacity, and hormone levels, exhibit circadian rhythms. Light signaling is the main stimulator of the mammalian circadian system. The photoperiod regulates the reproductive cycle of seasonal breeding animals, and the circadian clock plays a pivotal role in this process. However, the role of the clock in coordinating animal behavior and physiology in response to photoperiodic changes needs further investigation. The present study investigated the changes and correlation of behavioral activities, physiological indicators, and gene expression in female striped hamsters (Cricetulus barabensis) within 24 h under a 12L:12D photoperiod. We found that the daily rhythms of sleep-wake and open field were significant in hamsters. The expression of clock genes, melatonin receptor genes, and genes involved in general metabolism oscillated significantly in central and peripheral tissues (brain, hypothalamus, liver, ovary, and thymus) and was significantly associated with behavior and physiology. Our results revealed that the neuroendocrine system regulated the rhythmicity of behavior and physiology, and central and peripheral clock genes (Bmal1, Clock, Per1, Per2, Cry1, and Cry2), melatonin receptor genes (MT1, MT2, and GPR50), and metabolizing genes (SIRT1, FGF21, and PPARα) played important roles. Our results suggest that central and peripheral circadian clocks, melatonin receptors, and genes involved in general metabolism may play key roles in maintaining circadian behavior and metabolic homeostasis in striped hamsters. Our results may have important implication for rodent pest control.

Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut-Brain Regulation in Zebrafish.

There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut-brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 μg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1:EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 μg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut-brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.

Puberty in beef heifers: effects of prenatal and postnatal nutrition on the development of the neuroendocrine axis.

Reproductive maturation is a complex physiological process controlled by the neuroendocrine system and is characterized by an increase in gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) pulsatile secretion. Nutrition during early development is a key factor regulating puberty onset, which is defined as first ovulation in females. In heifers, nutrient restriction after weaning delays puberty, whereas elevated levels of nutrition and energy reserves advance reproductive maturation. Recent studies in cattle and other animal models have shown that the dam's nutrition during gestation can also program the neuroendocrine system in the developing fetus and has the potential to alter timing of puberty in the offspring. Among the metabolic signals that modulate brain development and control timing of puberty is leptin, a hormone produced primarily by adipocytes that communicates energy status to the brain. Leptin acts within the arcuate nucleus of the hypothalamus to regulate GnRH secretion via an upstream network of neurons that includes neurons that express neuropeptide Y (NPY), an orexigenic peptide with inhibitory effects on GnRH secretion, and alpha melanocyte-stimulating hormone (αMSH), an anorexigenic peptide with excitatory effects on GnRH neurons. Another important population of neurons are KNDy neurons, neurons in the arcuate nucleus that co-express the neuropeptides kisspeptin, neurokinin B, and dynorphin and have strong stimulatory effects on GnRH secretion. Our studies in beef heifers indicate that increased nutrition between 4 to 8 months of age advances puberty by diminishing NPY inhibitory tone and by increasing excitatory inputs of αMSH and kisspeptin, which collectively lead to increased GnRH/LH pulsatility. Our ongoing studies indicate that different planes of nutrition during gestation can alter maternal leptin concentrations and promote changes in the fetal brain. Nonetheless, at least in Bos indicus-influenced heifers, deficits programmed prenatally can be overcome by adequate postnatal nutrition without negatively impacting age at puberty or subsequent fertility.

Gender characteristics of depressive disorders: clinical, psychological, neurobiological and translational aspects

Various studies have indicated that the prevalence of depression is almost twice as high among women as among men. A major factor associated with the development of depression and other affective disorders are adverse and psychologically traumatic life events that contribute to changes in the neuroendocrine system, altering the capacity to adapt to stress. These changes are involved in the pathogenesis of mental disorders, along with genetic and other factors, and are to a significant degree regulated by gender dependent mechanisms. While women have a high prevalence of depressive disorders, men show a higher rate of alcohol and substance abuse. These differences in the epidemiology are most likely explained by different predisposition to mental disorders in men and women and a diversity of biological consequences to adverse life events. Taking this into account, there is a need for a critical review of currently used approaches to modeling depressive disorders in preclinical studies, including the use of animals of both sexes. Adaptation of experimental models and protocols taking into account gender characteristics of neuroendocrine changes in response to stress, as well as structural-morphological, electrophysiological, molecular, genetic and epigenetic features, will significantly increase the translational validity of experimental work.

Female zebra finches are more vulnerable to social isolation stress than males: Involvement of the nonapeptide system.

In group-living animals, chronic juvenile social isolation stress (SIS) can profoundly affect behavior and neuroendocrine regulation. However, its impact on social behavior in avian species, particularly regarding sex-specific neural circuit differences, remains underexplored. This study focused on zebra finches, a species known for its social clustering and cognitive abilities, to elucidate these influences. Results indicated that SIS significantly increased plasma corticosterone levels in females but not in males, suggesting a heightened stress response and susceptibility in females. Additionally, SIS disrupted sociality and flocking behavior in both sexes, with more severe impairments in social recognition observed in females. Mesotocin (MT) levels in the lateral septum of both sexes and in the ventromedial hypothalamus of females were found to mediate the SIS effect, while vasotocin (VT) levels within the social behavior network remained unchanged. Pharmacological interventions confirmed the critical role of MT in reversing SIS-induced impairments in sociality, flocking behavior, and social recognition, particularly in females. These findings highlight unique nucleus- and sex-dependent variations in MT and VT regulation, providing novel insights into the mechanisms governing avian social behavior. This study advances our understanding of the independent evolutionary pathways of neural circuits and neuroendocrine systems that modulate social behaviors across different taxonomic groups.