Childhood craniopharyngioma: a retrospective study of children followed in Hôpital Universitaire de Bruxelles.

Introduction: Craniopharyngiomas (CPs) are benign brain tumors accounting for 5 - 11% of intracranial tumors in children. These tumors often recur and can cause severe morbidity. Postoperative radiotherapy efficiently controls and prevents progression and recurrence. Despite advancements in neurosurgery, endocrinological, visual, and neuropsychological complications are common and significantly lower the quality of life of patients. Methods: We performed a retrospective study, including all patients younger than sixteen diagnosed with CP between July 1989 and August 2022 and followed up in Hôpital Universitaire de Bruxelles. Results: Nineteen children with CP were included, with median age of 7 years at first symptoms and 7.5 at diagnosis. Common symptoms at diagnosis were increased intracranial pressure (63%), visual impairment (47%), growth failure (26%), polyuria/polydipsia (16%), and weight gain (10.5%). As clinical signs at diagnosis, growth failure was observed in 11/18 patients, starting with a median lag of 1 year and 4 months before diagnosis. On ophthalmological examination, 27% of patients had papillary edema and 79% had visual impairment. When visual disturbances were found, the average preoperative volume was higher (p=0.039). Only 6/19 patients had gross total surgical resection. After the first neurosurgery, 83% experienced tumor recurrence or progression at a median time of 22 months. Eleven patients (73%) underwent postsurgical radiotherapy. At diagnosis, growth hormone deficiency (GHD) was the most frequent endocrine deficit (8/17) and one year post surgery, AVP deficiency was the most frequent deficit (14/17). Obesity was present in 13% of patients at diagnosis, and in 40% six months after surgery. There was no significant change in body mass index over time (p=0.273) after the first six months post-surgery. Conclusion: CP is a challenging brain tumor that requires multimodal therapy and lifelong multidisciplinary follow-up including hormonal substitution therapy. Early recognition of symptoms is crucial for prompt surgical management. The management of long-term sequelae and morbidity are crucial parts of the clinical path of the patients. The results of this study highlight the fundamental importance of carrying out a complete assessment (ophthalmological, endocrinological, neurocognitive) at the time of diagnosis and during follow-up so that patients can benefit from the best possible care.

Chorio-retinal vessel density in women affected by functional hypothalamic amenorrhea: a monocentric observational cross-sectional study to evaluate the impact of hypoestrogenism on chorio-retinal vascularization.

PURPOSE: Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization. RESULTS: OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% p value = 0.037 and in the whole area, at 5% p value = 0.028) and an increase in vascular density in the deep fovea (DVP) (at 10% p value = 0.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (p = 0.0002) and glucose values (p = 0.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, p value: 0.095) in the whole district. CONCLUSION: Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance.

Special considerations for the child with obesity: An Obesity Medicine Association (OMA) clinical practice statement (CPS) 2024.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details assessment and management of the child with overweight or obesity. The term "child" is defined as the child between 2 and 12 years of age. Because children are in a continual state of development during this age range, we will specify when our discussion applies to subsets within this age range. For the purposes of this CPS, we will use the following definitions: overweight in the child is a body mass index (BMI) ≥ 85th and <95th percentile, obesity in the child is a BMI ≥95th percentile, and severe obesity is a BMI ≥120% of the 95th percentile. Methods: The information and clinical guidance in this OMA Clinical Practice Statement are based on scientific evidence, supported by medical literature, and derived from the clinical perspectives of the authors. Results: This OMA Clinical Practice Statement provides an overview of prevalence of disease in this population, reviews precocious puberty in the child with obesity, discusses the current and evolving landscape of the use of anti-obesity medications in children in this age range, discusses the child with obesity and special health care needs, and reviews hypothalamic obesity in the child. Conclusions: This OMA Clinical Practice Statement on the child with obesity is an evidence based review of the literature and an overview of current recommendations. This CPS is intended to provide a roadmap to the improvement of the health of children with obesity, especially those with metabolic, physiological, psychological complications and/or special healthcare needs. This CPS addresses treatment recommendations and is designed to help the clinician with clinical decision making.

Feasibility, safety, and efficacy of dietary or lifestyle interventions for hypothalamic obesity: A systematic review.

BACKGROUND & AIMS: A dysfunctional hypothalamus may result in decreased feelings of satiety (hyperphagia), decreased energy expenditure, and increased fat storage as a consequence of hyperinsulinemia. Hypothalamic dysfunction may thus lead to morbid obesity and can be encountered in childhood as a consequence of congenital, genetic, or acquired disorders. There is currently no effective treatment for hypothalamic obesity (HO). However, comparable to alimentary obesity, dietary and lifestyle interventions may be considered the cornerstones of obesity treatment. We questioned the effect of dietary or lifestyle interventions for HO and systematically searched the literature for evidence on feasibility, safety, or efficacy of dietary or lifestyle interventions for childhood hypothalamic overweight or obesity. METHODS: A systematic search was conducted in MEDLINE (including Cochrane Library), EMBASE, and CINAHL (May 2023). Studies assessing feasibility, safety, or efficacy of any dietary or lifestyle intervention in children with hypothalamic overweight or obesity, were included. Animal studies, studies on non-diet interventions, and studies with no full text available were excluded. Because the number of studies to be included was low, the search was repeated for adults with hypothalamic overweight or obesity. Risk of bias was assessed with an adapted Cochrane Risk of Bias Tool. Level of evidence was assessed using the GRADE system. Descriptive data were described, as pooled-data analysis was not possible due to heterogeneity of included studies. RESULTS: In total, twelve studies were included, with a total number of 118 patients (age 1-19 years) of whom one with craniopharyngioma, one with ROHHAD-NET syndrome, 50 with monogenic obesity, and 66 with Prader-Willi syndrome (PWS). Four studies reported a dietary intervention as feasible. However, parents did experience difficulties with children still stealing food, and especially lowering carbohydrates was considered to be challenging. Seven studies reported on efficacy of a dietary intervention: a well-balanced restrictive caloric diet (30% fat, 45% carbohydrates, and 25% protein) and various hypocaloric diets (8-10 kcal/cm/day) were considered effective in terms of weight stabilization or decrease. No negative effect on linear growth was reported. Four studies reported on specific lifestyle interventions, of which three also included a dietary intervention. Combined dietary and lifestyle intervention resulted in decreased BMI, although BMI returned to baseline values on long-term. One additional study was identified in adults after brain trauma and showed a significant reduction in BMI in one out of eight patients after a combined dietary and lifestyle intervention. CONCLUSIONS: Hypocaloric diet or restrictive macronutrient diet with lower percentage of carbohydrates seems feasible and effective for childhood HO, although most of the studies had a high risk of bias, small cohorts without control groups, and were conducted in children with PWS only, compromising the generalizability. Lifestyle interventions only resulted in BMI decrease in short-term, indicating that additional guidance is needed to sustain its effect in the long-term. Literature on feasibility and efficacy of a dietary or lifestyle intervention for hypothalamic overweight or obesity is scarce, especially in children with acquired HO (following treatment for a suprasellar tumor). There is need for prospective (controlled) studies to determine which dietary and lifestyle intervention are most helpful for this specific patient group.

Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives.

The hypothalamic-pituitary-adrenal (HPA) axis is a critical component of the neuroendocrine system, playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus, hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis. This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture. Please cite this article as: Zheng JY, Zhu J, Wang Y, Tian ZZ. Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives. J Integr Med. 2024; Epub ahead of print.

What is the Vagal-Adrenal Axis?

Some recent publications have used the term "vagal-adrenal axis" to account for mechanisms involved in the regulation of inflammation by electroacupuncture. This concept proposes that efferent parasympathetic nerve fibers in the vagus directly innervate the adrenal glands to influence catecholamine secretion. Here, we discuss evidence for anatomical and functional links between the vagi and adrenal glands that may be relevant in the context of inflammation and its neural control by factors, including acupuncture. First, we find that evidence for any direct vagal parasympathetic efferent innervation of the adrenal glands is weak and likely artifactual. Second, we find good evidence that vagal afferent fibers directly innervate the adrenal gland, although their function is uncertain. Third, we highlight a wealth of evidence for indirect pathways, whereby vagal afferent signals act via the central nervous system to modify adrenal-dependent anti-inflammatory responses. Vagal afferents, not efferents, are thus the likely key to these phenomena.

Robot-assisted laser interstitial thermal therapy for drug-resistant epilepsy in hypothalamic hamartoma.

Hypothalamic hamartomas are congenital lesions of the hypothalamus, with a range of symptoms defined by lesion location. Common presenting symptoms include gelastic seizures and precocious puberty. When hamartoma-related seizures become resistant to medications, laser interstitial thermal therapy (LITT) has been shown to be an effective treatment. The authors present a case of robot-assisted LITT for a patient with an 11-year history of epilepsy due to hypothalamic hamartoma. In addition, they demonstrate the use of a stereotactic biopsy needle implemented during the procedure for possible biopsy of deep cranial lesions. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2415.

Analysis of the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea.

Objective: To investigate the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea (FHA).Methods: A retrospective cohort study was conducted to summarize the clinical and endocrine characteristics of 58 patients with FHA at initial diagnosis and to follow up the recovery of ovulation and spontaneous menstruation in the patients to investigate these biochemical indicators and their effects on recovery outcomes.Results: Among patients with FHA, 13.8% (8/58) and 15.5% (9/58) had above moderately severe depressive and severe anxiety symptoms respectively, and 25.9% (15/58) were at high risk for eating disorders. 34.5% (20/58) were included assessed as having recovered. The non-recovered group had higher scores on the Patient Health Questionnaire (PHQ-9) (p = .022) and higher scores on the Eating Attitude Test-26 (EAT-26) (p = .03) as well as bulimia and food preoccupation (p = .041). Follicle diameter >5 mm at initial diagnosis was an independent factor influencing recovery of reproductive axis function (odds ratio = 7.532; 95% confidence interval, 1.321-42.930; p = .023).Conculsions: Mood disorders and a certain risk of eating disorders were present in FHA.These, together with weight loss, endocrine and follicle size, could influence the outcome.

Development and validation of a novel treatment adherence, satisfaction and knowledge questionnaire (TASK-Q) for adult patients with hypothalamic-pituitary disorders.

PURPOSE: Successful treatment outcomes of adults with hypothalamic-pituitary disorders necessitate the adoption of intricate self-management behaviors, yet current scales for evaluating treatment adherence and satisfaction are inadequate for this patient group. This research introduces a novel treatment adherence, satisfaction and knowledge questionnaire (TASK-Q) developed specifically to identify patients' unmet needs in better assessing and managing these disorders. METHODS: The study was conducted in three phases: (1) generating items and testing content validity, (2) refining these items through a pilot study, and (3) a main study evaluating the psychometric properties of the TASK-Q scale among 262 adults in a Pituitary Nurse-led Clinic, with 152 (58%) patients completing the questionnaire. RESULTS: Exploratory factor analysis was used to test the factor structure and construct validity of the TASK-Q, revealing a 22-item scale divided into Satisfaction and Knowledge (17 items) and Adherence (5 items) subscales, and exhibiting high internal consistency (Cronbach's α = 0.90). Significant correlations were identified between satisfaction and knowledge (r = 0.67, p < 0.001), satisfaction and adherence (r = 0.23, p = 0.005), and knowledge and adherence (r = 0.43, p < 0.001). Complex treatment regimens, like daily growth hormone injections and adjusting glucocorticoids during illness, negatively affected adherence (p < 0.001). CONCLUSION: The TASK-Q is a novel validated scale that can effectively evaluate patients' perspectives on adherence, knowledge and satisfaction. Our findings highlight the significant impact of Advanced Nurse Practitioners in improving patient self-management behaviors, which likely leads to better treatment outcomes for people with hypothalamic-pituitary disorders.

Gyratory Seizures in Hypothalamic Hamartoma.

Gyratory seizures (GS) are a rare seizure type characterized by body rotation of ≥180° around its vertical axis. While GS have been documented in various epileptic syndromes, their occurrence in association with hypothalamic hamartomas (HH) has not been reported previously. This case report introduces the first documented instance of GS in a patient with a HH, a non-neoplastic tumor originating from the tuber cinereum. The patient, a 25-year-old female, with a history of recurrent seizures since childhood, initially presented with gelastic seizures, marked by inappropriate laughter, and subsequent evolution of symptoms including right oculocephalic version and gyratory seizures to the right side. Despite multiple antiepileptic medications, seizures persisted. Neuroimaging revealed a HH in the right hypothalamic region. The presence of polydactyly prompted consideration of Pallister Hall syndrome (PHS). PHS is an autosomal dominant condition linked to GLI3 gene mutations. While some features of PHS were absent in this case, the presence of both gelastic and gyratory seizures indicated the hypothalamus as the lesion site, despite inconclusive electroencephalogram findings. This report underscores the novel association of GS with HH and highlights the importance of considering PHS in patients with HH and polydactyly presenting with gelastic and gyratory seizures. Understanding GS in HH may offer insights into broader hypothalamic lesion-related epileptic phenomena.

Reducing neuroendocrine psychosocial stress response through socio-emotional dyadic but not mindfulness online training.

Introduction: Stress-related diseases pose significant health risks and show wide prevalence. Empirical evidence suggests that contemplative practices, such as socio-emotional dyadic mental exercises, hold promise in mitigating the adverse effects of stress and promoting psychosocial well-being. This study aimed to investigate the differential effects of two online contemplative mental training programs on the psychosocial stress response: the first involved classic mindfulness practices, while the second incorporated a socio-emotional dyadic approach known as Affect Dyad. Methods: The study was conducted as part of the longitudinal CovSocial project's phase 2 in the context of the COVID-19 pandemic. 140 individuals participated in the Trier Social Stress Task (TSST), where the psychosocial stress response was assessed with cortisol saliva samples and subjective stress questionnaires in a cross-sectional design after the active training groups finished their intervention period. Participants were randomly assigned to the socio-emotional training group, mindfulness-based training group, or a control group that did not receive any training. Both training programs consisted of a ten-week intervention period with a daily 12-minute app-based mental training practice and weekly 2-hour online coaching sessions led by mental training teachers. Results: Results showed that the socio-emotional Dyad group but not the mindfulness-based group exhibited significantly lower cortisol levels at 10, 20, 30, and 40 minutes after the stressor as well as lower total cortisol output compared to the control group during the TSST, indicating a reduced hormonal stress response to a social stressor. Subjective markers did not show differences between the three groups. Discussion: These findings indicate that the daily socio-emotional dyadic practice, which emphasizes non-judgmental and empathic listening as well as the acceptance of challenging emotions in the presence of others within one's daily life context, may serve as a protective factor against the adverse effects of psychosocial stress triggered by the fear of negative social judgments. Given the high prevalence of stress-related diseases, such online mental training programs based on dyadic practices may thus represent an efficient and scalable approach for stress reduction.

Reproductive function and behaviors: an update on the role of neural estrogen receptors alpha and beta.

Infertility is becoming a major public health problem, with increasing frequency due to medical, environmental and societal causes. The increasingly late age of childbearing, growing exposure to endocrine disruptors and other reprotoxic products, and increasing number of medical reproductive dysfunctions (endometriosis, polycystic ovary syndrome, etc.) are among the most common causes. Fertility relies on fine-tuned control of both neuroendocrine function and reproductive behaviors, those are critically regulated by sex steroid hormones. Testosterone and estradiol exert organizational and activational effects throughout life to establish and activate the neural circuits underlying reproductive function. This regulation is mediated through estrogen receptors (ERs) and androgen receptor (AR). Estradiol acts mainly via nuclear estrogen receptors ERα and ERß. The aim of this review is to summarize the genetic studies that have been undertaken to comprehend the specific contribution of ERα and ERß in the neural circuits underlying the regulation of the hypothalamic-pituitary-gonadal axis and the expression of reproductive behaviors, including sexual and parental behavior. Particular emphasis will be placed on the neural role of these receptors and the underlying sex differences.

Toxic Thyroid Adenoma Presenting as Apathetic Hyperthyroidism: A Case Report.

The thyroid gland is an essential endocrine organ that secretes hormones to regulate homeostasis across multiple organ systems throughout the body. It is actively regulated by the hypothalamic-pituitary-thyroid (HPT) axis, where negative feedback modulates the amounts of active hormone being released; thus, lesions that disrupt the proper functioning of this gland or its regulatory mechanisms can be destructive. Toxic thyroid adenomas are usually singular benign functioning nodules in the thyroid gland that cause thyrotoxicosis. Hyperthyroidism is commonly clinically silent, however, in most symptomatic cases, patients will be diagnosed based on abnormal laboratory findings and typical hyperthyroid symptoms. This case report examines an 81-year-old male with an extensive medical history who presented with complaints of new-onset generalized fatigue coupled with bilateral lower extremity muscle cramps. A positron emission tomography (PET) scan for other medical conditions incidentally noted mildly increased uptake in the thyroid gland, prompting a further investigation that resulted in a diagnosis of toxic thyroid adenoma. The patient responded well to treatment with methimazole and has remained in a euthyroid state.

Associations between adrenal gland volume and adipose tissue compartments - a whole body MRI study.

BACKGROUND: Obesity is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Effects of glucocorticoids on adipose tissues appear to depend on the specific adipose depot, in which they take place. In this study, we aimed to investigate the role of MRI-based adrenal gland volume as an imaging marker in association with different adipose tissue compartments. METHODS: The study cohort derives from the population-based research platform KORA (Cooperative Health Research in the Augsburg Region, Germany) MRI sub-study, a cross-sectional sub-study investigating the interactions between subclinical metabolic changes and cardiovascular disease in a study sample of 400 participants. Originally, eligible subjects underwent a whole-body MRI. MRI-based segmentations were performed manually and semi-automatically for adrenal gland volume, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epi- and pericardial fat and renal sinus fat. Hepatic and pancreatic lipid content were measured as pancreatic proton density fraction (PDFF) and MR-spectroscopic hepatic fat fraction (HFF). Multivariable linear regression analyses were performed. RESULTS: A number of 307 participants (56.2 ± 9.1 years, 60.3% male, 14.3% with type 2 diabetes (T2DM), 30.6% with obesity, 34.2% with hypertension) were included. In multivariable analyses, strong positive associations between adrenal gland volume and VAT, total adipose tissue (TAT) as well as HFF persisted after extensive step-wise adjustment for possible metabolic confounders (VAT: beta = 0.31, 95%-CI [0.71, 0.81], p < 0.001; TAT: beta = 0.14, 95%-CI [0.06, 0.23], p < 0.001; HFF: beta = 1.17, 95%-CI [1.04, 1.31], p = 0.009). In contrast, associations between adrenal gland volume and SAT were attenuated in multivariate analysis after adjusting for BMI. Associations between pancreatic PDFF, epi- and pericardial fat and renal sinus fat were mediated to a great extent by VAT (pancreatic PDFF: 72%, epicardial adipose tissue: 100%, pericardial adipose tissue: 100%, renal sinus fat: 81.5%). CONCLUSION: Our results found MRI-based adrenal gland volume as a possible imaging biomarker of unfavorable adipose tissue distribution, irrespective of metabolic risk factors. Thus, adrenal gland volume may serve as a potential MRI-based biomarker of metabolic changes and contributes to an individual characterization of metabolic states and individual risk stratification. Future studies should elucidate in a longitudinal study design, if and how HPA axis activation may trigger unfavorable adipose tissue distribution and whether and to which extent this is involved in the pathogenesis of manifest metabolic syndrome.

Hungry for relief: Potential for neurotensin to address comorbid obesity and pain.

Chronic pain and obesity frequently occur together. An ideal therapy would alleviate pain without weight gain, and most optimally, could promote weight loss. The neuropeptide neurotensin (Nts) has been separately implicated in reducing weight and pain but could it be a common actionable target for both pain and obesity? Here we review the current knowledge of Nts signaling via its receptors in modulating body weight and pain processing. Evaluating the mechanism by which Nts impacts ingestive behavior, body weight, and analgesia has potential to identify common physiologic mechanisms underlying weight and pain comorbidities, and whether Nts may be common actionable targets for both.

Prolonged stress alters the PC1/PC2 ratio in the rat lateral hypothalamus, implicating impaired orexin maturation.

Objectives: Stress elicits physiological and neuroendocrine responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis and lateral hypothalamus (LH). However, prolonged stress can dysregulate neuropeptide systems like orexin. This study investigated the effects of temporary and prolonged stress on HPA activity and orexin processing in the rat LH. Materials and Methods: Male Wistar rats were exposed to various stress repetitions. The stress paradigm is defined as short (acute; 1 day and mild; 3 days) and long (sub-chronic; 10 days and chronic; 21 days)-term 6 hr daily restraint stress. Plasma corticosterone (CORT) served as an index of HPA function. Expression of prepro-orexin and its processing enzymes prohormone convertases (PC) 1 and 2 was measured in LH tissues using semiquantitative RT-PCR. Results: The plasma level of CORT was elevated following mild, sub-chronic, and chronic, but not acute stress versus unstressed controls. The expression of prepro-orexin was heightened following all stress exposures. However, PC1 increased and PC2 decreased only after prolonged stress. The PC1/PC2 ratio was also selectively augmented with sub-chronic and chronic stress, implying impaired orexin maturation. Conclusion: Together, these data demonstrate that the HPA axis and lateral hypothalamic orexin system respond to stress based on stress repetition. Changes in orexin processing enzyme mRNA, exclusively after chronic stress, imply potential effects on peptide maturation, requiring confirmation of the orexin production at the protein level.

Dynamics in cortisol levels in Danio rerio fish under the influence of a synthetic analog of kisspeptin 1.

The effect of a synthetic analog of kisspeptin 1, a peptide involved in the regulation of the hypothalamicpituitary- gonadal (HPG) stress axis, on the cortisol level of Danio rerio fish was investigated. Kisspeptin 1 was administered at doses of 2 µg/kg and 8 µg/kg followed by resting for 1 h and 4 h. We found that kisspeptin at doses of 2 µg/kg and 8 µg/kg increased cortisol levels, with a significant spike in cortisol levels at 1 h post-injection.

PERK inhibitor (ISRIB) improves depression-like behavior by inhibitions of HPA-axis over-activation in mice exposed to chronic restraint stress.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.

History of the Development of Knowledge about the Neuroendocrine Control of Ovulation-Recent Knowledge on the Molecular Background.

The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the neuroendocrine background of the regulation of ovulation. We first describe the development of the pituitary gland, the structure of the median eminence (ME), the connection between the hypothalamus and the pituitary gland, the ovarian and pituitary hormones involved in ovulation, and the pituitary cell composition. We recall the pioneer physiological and morphological investigations that drove development forward. The description of the supraoptic-paraventricular magnocellular and tuberoinfundibular parvocellular systems and recognizing the role of the hypophysiotropic area were major milestones in understanding the anatomical and physiological basis of reproduction. The discovery of releasing and inhibiting hormones, the significance of pulse and surge generators, the pulsatile secretion of the gonadotropin-releasing hormone (GnRH), and the subsequent pulsatility of luteinizing (LH) and follicle-stimulating hormones (FSH) in the human reproductive physiology were truly transformative. The roles of three critical neuropeptides, kisspeptin (KP), neurokinin B (NKB), and dynorphin (Dy), were also identified. This review also touches on the endocrine background of human infertility and assisted fertilization.

Are There Biological Correlates of Response to Yoga-Based Interventions in Depression? A Critical Scoping Review.

Depression is the most common mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but the response to these treatments is often incomplete. Yoga-based interventions (YBIs) have been advocated by some researchers as a promising form of alternative treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. These studies were also critically reviewed to evaluate their methodological quality and any sources of bias. Nineteen studies were included in the review. Based on these studies, there is preliminary evidence that YBIs may be associated with increased serum brain-derived neurotrophic factor (BDNF) and reduced serum cortisol and interleukin-6 (IL-6) in patients with depression. However, many of these changes were also observed in the control arms, and the overall quality of the research was low. At present, it cannot be concluded that there are reliable biomarkers of response to YBIs in depression, though there are some potential biological correlates. Further advances in this field will depend critically on improvements in study design, particularly the minimization of sources of bias and the selection of more specific and sensitive biomarkers based on existing evidence from other treatment modalities.