Neuroendocrine Function Research Articles

The role of hypothalamic Orexin-A in stress-induced gastric dysmotility: An agonistic interplay with corticotropin releasing factor.

Central Orexin-A (OXA) modulates gastrointestinal (GI) functions and stress response. This study aimed to investigate whether OXA and CRF interact at hypothalamic level. Solid gastric emptying (GE), fecal output (FO), plasma corticosterone (CORT), and postprandial antro-pyloric motility were assessed in rats that underwent acute restraint stress (ARS) and pretreated with central OX1R and/or CRF receptor antagonists SB-334867 and alpha-helical CRF9,41 . Microdialysis was performed to assess ARS-induced release of OXA and CRF in PVN and LHA, respectively. Immunofluorescence labeling was performed to detect the stress-induced changes in OXA and to assess the hypothalamic distribution of OX1R and CRF1/2 receptors. ARS-induced c-Fos immunoreactivity was evaluated in PVN and LHA of rats received OX1R and CRF receptor antagonists. ARS delayed GE by disturbing the coordination of antro-pyloric contractions while stimulating FO and CORT secretion. ARS-induced alterations in GE, FO, plasma CORT, and antro-pyloric motility were attenuated by OX1R and/or CRF receptor antagonists, however, these changes were completely restored in rats received both antagonists. ARS stimulated release of OXA and CRF which were significantly attenuated by α-CRF9,41 and SB-334867, respectively. The OX1R was detected in CRF-immunoreactive cells, whereas dense expression of CRF2 receptor but not CRF1 was observed in LHA. ARS remarkably increased OXA immunoreactivity in LHA. ARS-induced c-Fos expression in LHA and PVN was abolished by α-CRF9,41 and SB-334867, respectively. Our findings suggest a reciprocal contribution of OXA and CRF which seems to be involved in the mediation of stress-induced alterations in neuroendocrine and GI motor functions.

Paroxysmal Sympathetic Hyperactivity After Acquired Brain Injury: An Integrative Review of Diagnostic and Management Challenges.

Paroxysmal sympathetic hyperactivity (PSH) mainly occurs after acquired brain injury (ABI) and often presents with high fever, hypertension, tachycardia, tachypnea, sweating, and dystonia (increased muscle tone or spasticity). The pathophysiological mechanisms of PSH are not fully understood. Currently, there are several views: (1) disconnection theory, (2) excitatory/inhibitory ratio, (3) neuroendocrine function, and (4) neutrophil extracellular traps. Early diagnosis of PSH remains difficult, given the low specificity of its diagnostic tools and unclear pathogenesis. According to updated case analyses in recent years, PSH is now more commonly observed in patients with stroke, with tachycardia and hypertension as the main clinical manifestations, which is not fully consistent with previous data. To date, the PSH Assessment Measure tool is optimal for the early identification of PSH and stratification of symptom severity. Clinical strategies for the management of PSH are divided into three main points: (1) reduction of stimulation, (2) reduction of sympathetic excitatory afferents, and (3) inhibition of the effects of sympathetic hyperactivity on target organs. However, use of drugs and standards have not yet been harmonized. Further investigation on the relationship between PSH severity and long-term neurological prognosis in patients with ABI is required. This review aimed to determine the diagnostic and management challenges encountered in PSH after ABI.

Heart failure after left atrial appendage occlusion: insights from the LAAOS-III randomized trial

Abstract Background Left atrial appendage removal or occlusion (LAAO) might increase the risk for heart failure (HF) due to the loss of the LAA`s reservoir function, active contraction and neuroendocrine function. Purpose To investigate the incidence of HF hospitalizations and/or HF related death after LAAO in the Left Atrial Appendage Occlusion Study (LAAOS III). Methods In LAAOS III, 4811 patients with atrial fibrillation (AF) and a CHA2DS2-VASc score ≥2 were randomized to undergo or not undergo surgical LAAO during cardiac surgery for another indication. We compared the incidence of a composite endpoint of HF hospitalizations and HF related death between the two randomized groups (LAAO vs no-LAAO). We also pre-specified subgroups including: sex, age, BMI, surgery type, concomitant AF ablation, prior history of HF, history of hypertension, diabetes, prior myocardial infarction, left ventricular ejection fraction, sinus rhythm and occlusion method. Results We included 2379 patients in the LAAO and 2391 patients in the no-LAAO group. Overall, mean age was 71 years, 67% were male and 57% had prior HF. Baseline characteristics including drug treatment were balanced between the groups. Over a mean follow-up of 3.8 years, 395 (8.3%) patients met the primary HF endpoint: 209 (8.8%) in the LAAO group and 186 (7.8%) in the no-LAAO group. We did not find a significant difference for the primary endpoint between the randomized groups (Hazard ratio [95% confidence intervals] 1.13 [0.93-1.37], p=0.233) (Figure). The only significant subgroup interaction was for concomitant AF ablation (p for interaction = 0.004). Patients in the LAAO group without concomitant AF ablation had a higher risk for the primary endpoint (HR [95% CI] 1.37 [1.08-1.74], p=0.009) than patients with ablation (HR [95% CI] 0.74 [0.51-1.06], p=0.097). Conclusion LAAO did not increase the risk for a combined endpoint of HF hospitalizations and HF related death in patients with AF. Patients with concomitant AF ablation might have lower risk for the combined endpoint.Figure

The 2023 American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine Pediatric and Adult Brain Death/Death by Neurologic Criteria Determination Consensus Guidelines: What the Critical Care Team Needs to Know.

Guidelines for brain death/death by neurologic criteria (BD/DNC) determination were revised to provide a consistent and updated approach to BD/DNC evaluation across all ages by the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine. This article is intended to complement the guidelines and highlight aspects relevant to the critical care community; the actual guidelines should be used to update hospital protocols and dictate clinical practice. Because BD/DNC evaluations are conducted in the ICU, it is essential for members of the critical care community to familiarize themselves with these guidelines. The fundamental concept of BD/DNC has not changed; BD/DNC is permanent loss of function of the brain as a whole, including the brain stem, resulting in coma, brainstem areflexia, and apnea in the setting of an adequate stimulus. The BD/DNC evaluation requires a sufficient observation period to ensure there is no chance of recovery, followed by exclusion of potentially confounding conditions like hypothermia, hypotension, severe metabolic disturbances, or medication effects. Specific guidance is provided for patients who were treated with therapeutic hypothermia or medical or surgical interventions to manage intracranial hypertension. The guidelines outline a structured and meticulous neurologic examination and detail the responses consistent with BD/DNC. A protocol is provided for how to safely perform apnea testing, including modifications needed for patients on extracorporeal membrane oxygenation. Controversial issues such as consent, BD/DNC evaluation in pregnancy, preservation of neuroendocrine function, and primary posterior fossa injuries are addressed. The ultimate goal is to ensure a consistent and accurate approach to BD/DNC evaluation in patients of all ages, fostering public trust in the medical community's ability to determine death. By adhering to these guidelines, critical care clinicians can confidently navigate the challenging aspects of BD/DNC determination.

Probiotic Lactobacillus rhamnosus alleviates the neurotoxicity of microcystin-LR in zebrafish (Danio rerio) through the gut-brain axis

Microcystin-LR (MCLR) is one of the most toxic cyanobacterial toxins and is harmful to the central nervous system of fish. Probiotic additives can improve neuroendocrine function in fish. Although both MCLR and probiotics aim at the nervous system, whether they interact with each other and the mechanisms remain unexplored. In the present study, 4-month-old zebrafish were exposed to 0, 2.2, and 22 μg/L of MCLR for 28 days with or without the probiotic L. rhamnosus. We found that MCLR exposure could inhibit the swimming speed of zebrafish, while the presence of L. rhamnosus mitigated this abnormality. To elucidate the mechanism of how L. rhamnosus alleviates MCLR-induced neurotoxicity, we examined the bioaccumulation of MCLR, changes in neurotransmitters, immune biochemical indicators, and hormone content of the hypothalamic-pituitary-interrenal (HPI) axis in zebrafish along the gut-brain axis. Our results showed L. rhamnosus could reverse the abnormal swimming behavior and eventually alleviate neurotoxicity in zebrafish by modulating intestinal and brain neural signaling, neuroinflammation, and HPI axis responses. This study provides implications for the application of probiotics in the aquaculture industry.

Intracranial germ cell tumors: a view of the endocrinologist.

Intracranial germ cell tumors (iGCTs) are rare malignant neoplasms that mainly affect children and adolescents. The incidence, clinical presentation, and prognosis of iGCTs exhibit high heterogeneity. Previous studies have primarily focused on eliminating tumors, reducing tumor recurrence, and improving survival rates, while neglecting the impact of the tumors and their treatment on neuroendocrine function. Throughout the entire course of the disease, neuroendocrine dysfunction may occur and is frequently overlooked by oncologists, neurosurgeons, and radiologists. Endocrinologists, however, are more interested in this issue and have varying priorities at different stages of the disease. From onset to the diagnostic phase, most patients with iGCTs may present with symptoms related to impaired neuroendocrine function, or even experience these symptoms as their first indication of the condition. Particularly, a minority of patients with sellar/suprasellar lesions may exhibit typical imaging features and elevated tumor markers long after the onset of initial symptoms. This can further complicate the diagnosis process. During the peritumor treatment phase, the neuroendocrine function shows dynamic changes and needs to be evaluated dynamically. Once diabetes insipidus and dysfunction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes occur, hormone replacement therapy should be administered promptly to ensure successful tumor treatment for the patient. Subsequently, during the long-term management phase after the completion of tumor treatment, the evaluation of growth and development as well as corresponding hormone replacement therapy are the most concerning and complex issues. Thus, this paper reviews the interest of endocrinologists in iGCTs at different stages.

Cocaine intake correlates with risk-taking behavior and affects estrous cycling in female Sprague-Dawley rats.

Navigating complex decisions and considering their relative risks and rewards is an important cognitive ability necessary for survival. However, use of and dependence on illicit drugs can result in long-lasting changes to this risk/reward calculus in individuals with substance use disorder. Recent work has shown that chronic exposure to cocaine causes long-lasting increases in risk taking in male and female rats, but there are still significant gaps in our understanding of the relationship between cocaine use and changes in risk taking. For example, it is unclear whether the magnitude of cocaine intake dictates the extent to which risk taking is altered. To address this, male and female Sprague-Dawley rats underwent cocaine (or sucrose) self-administration and, following a period of abstinence, were trained and tested in a rodent model of risky decision making. In this behavioral task, rats made discrete-trial choices between a lever associated with a small food reward (i.e., "safe" option) and a lever associated with a larger food reward accompanied by a variable risk of footshock delivery (i.e., "risky" option). Surprisingly, and in contrast to prior work in Long-Evans rats, there were no effects of cocaine self-administration on choice of the large, risky reward (i.e., risk taking) during abstinence in males or females. There was, however, a significant relationship between cocaine intake and risk taking in female rats, with greater intake associated with greater preference for the large, risky reward. Relative to their sucrose counterparts, female rats in the cocaine group also exhibited irregular estrous cycles, characterized by prolonged estrus and/or diestrus phases. Collectively, these data suggest that there may be strain differences in the effects of cocaine on risk taking and highlight the impact that chronic cocaine exposure has on hormonal cyclicity in females. Future work will focus on understanding the neural mechanisms underlying cocaine's intake-dependent effects on risk taking in females, and whether this is directly related to cocaine-induced alterations in neuroendocrine function.

Bedside to bench: the outlook for psychedelic research.

There has recently been a resurgence of interest in psychedelic compounds based on studies demonstrating their potential therapeutic applications in treating post-traumatic stress disorder, substance abuse disorders, and treatment-resistant depression. Despite promising efficacy observed in some clinical trials, the full range of biological effects and mechanism(s) of action of these compounds have yet to be fully established. Indeed, most studies to date have focused on assessing the psychological mechanisms of psychedelics, often neglecting the non-psychological modes of action. However, it is important to understand that psychedelics may mediate their therapeutic effects through multi-faceted mechanisms, such as the modulation of brain network activity, neuronal plasticity, neuroendocrine function, glial cell regulation, epigenetic processes, and the gut-brain axis. This review provides a framework supporting the implementation of a multi-faceted approach, incorporating in silico, in vitro and in vivo modeling, to aid in the comprehensive understanding of the physiological effects of psychedelics and their potential for clinical application beyond the treatment of psychiatric disorders. We also provide an overview of the literature supporting the potential utility of psychedelics for the treatment of brain injury (e.g., stroke and traumatic brain injury), neurodegenerative diseases (e.g., Parkinson's and Alzheimer's diseases), and gut-brain axis dysfunction associated with psychiatric disorders (e.g., generalized anxiety disorder and major depressive disorder). To move the field forward, we outline advantageous experimental frameworks to explore these and other novel applications for psychedelics.

Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.

Prolonged inflammatory expression within the central nervous system (CNS) is recognized by the brain as a molecular signal of "sickness", that has knock-on effects to the blood-brain barrier, brain-spinal barrier, blood-cerebrospinal fluid barrier, neuro-axonal structures, neurotransmitter activity, synaptic plasticity, neuroendocrine function, and resultant systemic symptomatology. It is concurred that the inflammatory process associated with cancer and cancer treatments underline systemic symptoms present in a large portion of survivors, although this concept is largely theoretical from disparate and indirect evidence and/or clinical anecdotal reports. We conducted a proof-of-concept study to link for the first time late non-CNS cancer survivors presenting chronic systemic symptoms and the presence of centralized inflammation, or neuroinflammation, using TSPO-binding PET tracer [11 C]-PBR28 to visualize microglial activation. We compared PBR28 SUVR in 10 non-CNS cancer survivors and 10 matched healthy controls. Our data revealed (1) microglial activation was significantly higher in caudate, temporal, and occipital regions in late non-central nervous system/CNS cancer survivors compared to healthy controls; (2) increased neuroinflammation in cancer survivors was not accompanied by significant differences in plasma cytokine markers of peripheral inflammation; (3) increased neuroinflammation was not accompanied by reduced fractional anisotropy, suggesting intact white matter microstructural integrity, a marker of neurovascular fiber tract organization; and (4) the presentation of chronic systemic symptoms in cancer survivors was significantly connected with microglial activation. We present the first data empirically supporting the concept of a peripheral-to-centralized inflammatory response in non-CNS cancer survivors, specifically those previously afflicted with head and neck cancer. Following resolution of the initial peripheral inflammation from the cancer/its treatments, in some cases damage/toxification to the central nervous system occurs, ensuing chronic systemic symptoms.

Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy.

Among its pleiotropic properties, gender-affirming hormone therapy (GHT) affects regional brain volumes. The hypothalamus, which regulates neuroendocrine function and associated emotional and cognitive processes, is an intuitive target for probing GHT effects. We sought to assess changes to hypothalamus and hypothalamic subunit volumes after GHT, thereby honouring the region's anatomical and functional heterogeneity. Individuals with gender dysphoria and cisgender controls underwent 2 MRI measurements, with a median interval of 145 days (interquartile range [IQR] 128.25-169.75 d, mean 164.94 d) between the first and second MRI. Transgender women (TW) and transgender men (TM) underwent the first MRI before GHT and the second MRI after approximately 4.5 months of GHT, which comprised estrogen and anti-androgen therapy in TW or testosterone therapy in TM. Hypothalamic volumes were segmented using FreeSurfer, and effects of GHT were tested using repeated-measures analysis of covariance. The final sample included 106 participants: 38 TM, 15 TW, 32 cisgender women (CW) and 21 cisgender men (CM). Our analyses revealed group × time interaction effects for total, left and right hypothalamus volume, and for several subunits (left and right inferior tubular, left superior tubular, right anterior inferior, right anterior superior, all p corr < 0.01). In TW, volumes decreased between the first and second MRI in these regions (all p corr ≤ 0.01), and the change from the first to second MRI in TW differed significantly from that in CM and CW in several subunits (p corr < 0.05). We did not address the influence of transition-related psychological and behavioural changes. Our results suggest a subunit-specific effect of GHT on hypothalamus volumes in TW. This finding is in accordance with previous reports of positive and negative effects of androgens and estrogens, respectively, on cerebral volumes.

Ghrelin Action in the PVH of Male Mice: Accessibility, Neuronal Targets, and CRH Neurons Activation.

The hormone ghrelin displays several well-characterized functions, including some with pharmaceutical interest. The receptor for ghrelin, the growth hormone secretagogue receptor (GHSR), is expressed in the hypothalamic paraventricular nucleus (PVH), a critical hub for the integration of metabolic, neuroendocrine, autonomic, and behavioral functions. Here, we performed a neuroanatomical and functional characterization of the neuronal types mediating ghrelin actions in the PVH of male mice. We found that fluorescent ghrelin mainly labels PVH neurons immunoreactive for nitric oxide synthase 1 (NOS1), which catalyze the production of nitric oxide [NO]). Centrally injected ghrelin increases c-Fos in NOS1 PVH neurons and NOS1 phosphorylation in the PVH. We also found that a high dose of systemically injected ghrelin increases the ghrelin level in the cerebrospinal fluid and in the periventricular PVH, and induces c-Fos in NOS1 PVH neurons. Such a high dose of systemically injected ghrelin activates a subset of NOS1 PVH neurons, which do not express oxytocin, via an arcuate nucleus-independent mechanism. Finally, we found that pharmacological inhibition of NO production fully abrogates ghrelin-induced increase of calcium concentration in corticotropin-releasing hormone neurons of the PVH whereas it partially impairs ghrelin-induced increase of plasma glucocorticoid levels. Thus, plasma ghrelin can directly target a subset of NO-producing neurons of the PVH that is involved in ghrelin-induced activation of the hypothalamic-pituitary-adrenal neuroendocrine axis.

Case control study: G-allele of rs4244165 in JAK1 gene correlated with high-level brief psychiatric rating scale in bipolar patients.

Bipolar disorder (BD) is a chronic and clinically complex disease, characterized by pathological disturbances in mood and energy. Cytokines can access the brain and their signaling pathways affect brain functions, such as neurotransmitter metabolism, neuroendocrine function, neural/synaptic plasticity, and mood neural circuitry. JAK 1 is the most common phosphorylation protein combined with the tyrosine kinase cytokine receptors; therefore, we investigated the association between the Janus family kinase 1 (JAK1) gene polymorphisms (rs2780895, rs4244165, and rs17127024) and susceptibility to BD. The case study population included 93 patients diagnosed with BD and 112 healthy controls, selected from the central coastal region of Tunisia. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate these 3 JAK1 polymorphisms. We compared the sociodemographic and clinical parameters of 3 genotypes of this single nucleotide polymorphisms rs2780895, rs4244165, and rs17127024 of the JAK1 gene. The frequencies of the 3 genotypes were similar in the patient and control groups. One-way analysis of variance revealed a significant variation in rs4244165. After hospitalization, the average of the brief psychiatric rating scale score was significantly higher for the wild-type GG genotype than that for the double-mutation TT genotype (31.23% vs 22.85%, P = .043). The least significant difference post hoc test also showed a significant difference between the GG and TT genotypes at both hospital admission (P = .001) and after hospitalization (P = .012), with the GG genotype being associated with a higher brief psychiatric rating scale score. Haplotypic analysis revealed that the wild-type haplotype with the highest frequency (46.62%) was CTG. Our results showed no association between the 3 studied positions and bipolar disorder. However, the G-allele of rs4244165 in JAK1 is associated with the highest level of the brief psychiatric rating scale in patients with bipolar disorder. The JAK/signal transducer and activator of transcription pathway is an interesting therapeutic route that requires further investigations. Studying their regulatory regions can provide a clearer picture of all the interactions involved in the regulation of genetic expression in response to treatment.

GABA-immunoreactive neurons in the Central Nervous System of the viviparous teleost Poecilia sphenops

Gamma-aminobutyric acid (GABA) functions as the primary inhibitory neurotransmitter within the central nervous system (CNS) of vertebrates. In this study, we examined the distribution pattern of GABA-immunoreactive (GABA-ir) cells and fibres in the CNS of the viviparous teleost Poecilia sphenops using immunofluorescence method. GABA immunoreactivity was seen in the glomerular, mitral, and granular layers of the olfactory bulbs, as well as in most parts of the dorsal and ventral telencephalon. The preoptic area consisted of a small cluster of GABA-ir cells, whereas extensively labelled GABA-ir neurons were observed in the hypothalamic areas, including the paraventricular organ, tuberal hypothalamus, nucleus recessus lateralis, nucleus recessus posterioris, and inferior lobes. In the thalamus, GABA-positive neurons were only found in the ventral thalamic and central posterior thalamic nuclei, whereas the dorsal part of the nucleus pretectalis periventricularis consisted of a few GABA-ir cells. GABA-immunoreactivity was extensively seen in the alar and basal subdivisions of the midbrain, whereas in the rhombencephalon, GABA-ir cells and fibres were found in the cerebellum, motor nucleus of glossopharyngeal and vagal nerves, nucleus commissuralis of Cajal, and reticular formation. In the spinal cord, GABA-ir cells and fibres were observed in the dorsal horn, ventral horn, and around the central canal. Overall, the extensive distribution of GABA-ir cells and fibres throughout the CNS suggests several roles for GABA, including the neuroendocrine, viscerosensory, and somatosensory functions, for the first time in a viviparous teleost.

Research Note: Association of LEPR gene polymorphism with growth and carcass traits in Savimalt and French Giant meat-type quails

The leptin receptor (LEPR) gene is a member of the class I cytokine receptor family, which plays an important role in weight regulation, fat accumulation and neuroendocrine function in animals. This study aimed to explore the association of single nucleotide polymorphisms (SNPs) of the LEPR gene with growth and carcass traits in meat-type quail by PCR amplification and DNA direct sequencing. In this study, genomic DNA was extracted from blood samples of 36 female Savimalt (SV) quails and 49 female French Giant (FG) quails. Growth traits (measured at 3 or 5 wk) and carcass traits (measured at 5 wk) were used for LEPR gene association analysis. The results showed the existence of 9 SNPs (T81C, G90T, C187A, A191G, A219G, G258A, C286T, G346A, and G373A) of the LEPR gene in the 2 quail strains. The statistical analyses indicated that these SNPs of LEPR gene was significantly associated with shank circumference (SC), shank length (SL), breastbone length (BBL), heart rate (HR), and whole net carcass rate (WNCR) of FG (P < 0.05); chest width (CW), body length (BL), leg muscle rate (LMR), whole net carcass rate (WNCR), and heart rate (HR) of SV (P < 0.05). While haplotypes showed significant effect on SL, BBL, heart weight (HW), WNCR, and HR of FG (P < 0.05). Therefore, the LEPR gene may serve as a molecular genetic marker for improving growth and carcass traits in quails.

Adipose Tissues from Human and Bat-Derived Cell Lines Support Ebola Virus Infection.

Ebola virus is a zoonotic pathogen with a geographic range covering diverse ecosystems that are home to many potential reservoir species. Although researchers have detected Ebola virus RNA and serological evidence of previous infection in different rodents and bats, the infectious virus has not been isolated. The field is missing critical knowledge about where the virus is maintained between outbreaks, either because the virus is rarely encountered, overlooked during sampling, and/or requires specific unknown conditions that regulate viral expression. This study assessed adipose tissue as a previously overlooked tissue capable of supporting Ebola virus infection. Adipose tissue is a dynamic endocrine organ helping to regulate and coordinate homeostasis, energy metabolism, and neuroendocrine and immune functions. Through in vitro infection of human and bat (Eptesicus fuscus) brown adipose tissue cultures using wild-type Ebola virus, this study showed high levels of viral replication for 28 days with no qualitative indicators of cytopathic effects. In addition, alterations in adipocyte metabolism following long-term infection were qualitatively observed through an increase in lipid droplet number while decreasing in size, a harbinger of lipolysis or adipocyte browning. The finding that bat and human adipocytes are susceptible to Ebola virus infection has important implications for potential tissue tropisms that have not yet been investigated. Additionally, the findings suggest how the metabolism of this tissue may play a role in pathogenesis, viral transmission, and/or zoonotic spillover events.

Hormonal Imbalances in Prader-Willi and Schaaf-Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals.

The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of which are affected in patients with Prader-Willi (PWS) and Schaaf-Yang syndrome (SYS). PWS is caused by paternal deletion, maternal uniparental disomy, or imprinting defects that lead to loss of expression of a maternally imprinted region of chromosome 15 encompassing non-coding RNAs and five protein-coding genes; SYS patients have a mutation in one of them, MAGEL2. Throughout life, PWS and SYS patients suffer from musculoskeletal deficiencies, intellectual disabilities, and hormonal abnormalities, which lead to compulsive behaviors like hyperphagia and temper outbursts. Management of PWS and SYS is mostly symptomatic and cures for these debilitating disorders do not exist, highlighting a clear, unmet medical need. Research over several decades into the molecular and cellular roles of PWS genes has uncovered that several impinge on the neuroendocrine system. In this review, we will discuss the expression and molecular functions of PWS genes, connecting them with hormonal imbalances in patients and animal models. Besides the observed hormonal imbalances, we will describe the recent findings about how the loss of individual genes, particularly MAGEL2, affects the molecular mechanisms of hormone secretion. These results suggest that MAGEL2 evolved as a mammalian-specific regulator of hypothalamic neuroendocrine function.

Glucocorticoids and Their Receptor Isoforms: Roles in Female Reproduction, Pregnancy, and Foetal Development.

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism's response to stressful stimuli. Glucocorticoids acting via glucocorticoid receptors (GRs) play a role in fertility, reproduction, placental function, and foetal development. GRs are ubiquitously expressed throughout the female reproductive system and regulate normal reproductive function. Stress-induced glucocorticoids have been shown to inhibit reproduction and affect female gonadal function by suppressing the hypothalamic-pituitary-gonadal (HPG) axis at each level. Furthermore, during pregnancy, a mother's exposure to prenatal stress or external glucocorticoids can result in long-lasting alterations to the foetal HPA and neuroendocrine function. Several GR isoforms generated via alternative splicing or translation initiation from the GR gene have been identified in the mammalian ovary and uterus. The GR isoforms identified include the splice variants, GRα and GRβ, and GRγ and GR-P. Glucocorticoids can exert both stimulatory and inhibitory effects and both pro- and anti-inflammatory functions in the ovary, in vitro. In the placenta, thirteen GR isoforms have been identified in humans, guinea pigs, sheep, rats, and mice, indicating they are conserved across species and may be important in mediating a differential response to stress. Distinctive responses to glucocorticoids, differential birth outcomes in pregnancy complications, and sex-based variations in the response to stress could all potentially be dependent on a particular GR expression pattern. This comprehensive review provides an overview of the structure and function of the GR in relation to female fertility and reproduction and discusses the changes in the GR and glucocorticoid signalling during pregnancy. To generate this overview, an extensive non-systematic literature search was conducted across multiple databases, including PubMed, Web of Science, and Google Scholar, with a focus on original research articles, meta-analyses, and previous review papers addressing the subject. This review integrates the current understanding of GR variants and their roles in glucocorticoid signalling, reproduction, placental function, and foetal growth.

Role of cytokines and reactive oxygen species in brain aging

Aging is a complex process that produces profound effects on the brain. Although a number of external factors can promote the initiation and progression of brain aging, peripheral and central changes in the immune cells with time, also play an important role. Immunosenescence, which is an age-associated decline in immune function and Inflammaging, a low-grade inflammatory state in the aging brain contribute to an elevation in cytokine and reactive oxygen species production. In this review, we focus on the pro-inflammatory state that is established in the brain as a consequence of these two phenomena and the resulting detrimental changes in brain structure, function and repair that lead to a decline in central and neuroendocrine function.

Comparison of different predominant lesions in intracranial bifocal germ cell tumors to predict neuroendocrine outcomes.

Intracranial germ cell tumors frequently arise from the midline of the brain, occasionally presenting as bifocal diseases. The predominant lesion might affect clinical characteristics and neuroendocrine outcomes. A retrospective cohort study involving 38 patients with intracranial bifocal germ cell tumors was performed. Twenty-one patients were assigned to the sellar-predominant group, while the other 17 patients were assigned to the non-sellar-predominant group. Differences in gender ratio, age, manifestation, the incidence of metastasis, the incidence of elevated tumor markers, human chorionic gonadotropin levels in serum and in cerebrospinal fluid, diagnostic method, and tumor type were not significant between the sellar-predominant group and the non-sellar-predominant group. Before treatment, the sellar-predominant group had a higher incidence of adenohypophysis hormone deficiencies and central diabetes insipidus than those of the non-sellar-predominant group, without significant differences. After multidisciplinary therapy, the sellar-predominant group also had a higher incidence of adenohypophysis hormone deficiencies and central diabetes insipidus than those of the non-sellar-predominant group. The differences in the hypothalamic-pituitary-adrenal (HPA) axis impairment (P = 0.008), hypothalamic-pituitary-thyroid (HPT) axis impairment (P = 0.048), and hypothalamic-pituitary-gonad (HPG) axis impairment (P = 0.029) were significant between sellar-predominant group and non-sellar-predominant group, while the others were not. At median 6 (3, 43) months of follow-up visit, sellar-predominant group had a higher incidence of adenohypophysis hormone deficiencies than those of non-sellar-predominant group. The differences in the HPA impairment (P = 0.002), HPT impairment (P = 0.024), and HPG impairment (P < 0.000) were significant, while the others were not. Further comparison of the neuroendocrine function between different subtypes of sellar-predominant patients indicated that the differences in adenohypophysis hormone deficiencies and central diabetes insipidus were not significant between the two subtype groups. Bifocal patients with different predominant lesions present similar manifestations and neuroendocrine disorders before treatment. Non-sellar-predominant patients would have better neuroendocrine outcomes after tumor treatment. The distinction of the predominant lesion in patients with bifocal intracranial germ cell tumor plays a valuable role in predicting neuroendocrine outcomes, as well as in optimizing long-term neuroendocrine management during survival time.

Juvenile xanthogranuloma as a differential diagnosis for sellar and suprasellar lesions in child: Case report and review of literature

Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. Its systemic form affects 4% of patients. Lesions in the Central Nervous System (CNS) occur in 2% of systemic cases. Sellar JXG should be one of the differential diagnoses for sellar lesions in young. This is a 15-year-old patient with non-specific headache, progressive visual loss and magnetic resonance imaging showing sellar lesion with suprasellar extension. The patient underwent microsurgery by pterional craniotomy with partial resection of the tumor. Pathology evidenced JXG. It progressively evolved with impairment of neuroendocrine functions, new lesions in different CNS locations and death two years after diagnosis. Sellar JXG without cutaneous manifestations is rare. There are no specific findings of the disease. Diagnosis requires additional tests, being defined by pathological analysis. Total resection presents a greater potential control comparing to partial resection. Even so, some patients may have progressive disease with poor clinical outcome.