Hypothalamic Regions Research Articles

Hypothalamic regulation of hippocampal CA1 interneurons by the supramammillary nucleus

The hypothalamic supramammillary nucleus (SuM) projects heavily to the hippocampus to regulate hippocampal activity and plasticity. Although the projections from the SuM to the dentate gyrus (DG) and CA2 have been extensively studied, whether the SuM projects to CA1, the main hippocampal output region, is unclear. Here, we report a glutamatergic pathway from the SuM that selectively excites CA1 interneurons in the border between the stratum radiatum (SR) and the stratum lacunosum-moleculare (SLM). We find that the SuM projects selectively to a narrow band in the CA1 SR/SLM and monosynaptically excites SR/SLM interneurons, including vasoactive intestinal peptide-expressing (VIP+) and neuron-derived neurotrophic factor-expressing (NDNF+) cells, but completely avoids making monosynaptic contacts with CA1 pyramidal neurons (PNs) or parvalbumin-expressing (PV+) or somatostatin-expressing (SOM+) cells. Moreover, SuM activation drives spikes in most SR/SLM interneurons to suppress CA1 PN excitability. Taken together, our findings reveal that the SuM can directly regulate hippocampal output region CA1, bypassing CA2, CA3, and the DG.

Regional response to light illuminance across the human hypothalamus.

Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.3±2.9 y) were completing two auditory cognitive tasks. We find that, during both the executive and emotional tasks, higher illuminance triggered an activity increase over the posterior part of the hypothalamus, which includes part of the tuberomamillary nucleus and the posterior part of the lateral hypothalamus. In contrast, increasing illuminance evoked a decrease in activity over the anterior and ventral parts of the hypothalamus, encompassing notably the suprachiasmatic nucleus and another part of the tuberomammillary nucleus. Critically, the performance of the executive task was improved under higher illuminance and was negatively correlated with the activity of the posterior hypothalamus area. These findings reveal the distinct local dynamics of different hypothalamus regions that underlie the impact of light on cognition.

Regional response to light illuminance across the human hypothalamus

Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.3±2.9 y) were completing two auditory cognitive tasks. We find that, during both the executive and emotional tasks, higher illuminance triggered an activity increase over the posterior part of the hypothalamus, which includes part of the tuberomamillary nucleus and the posterior part of the lateral hypothalamus. In contrast, increasing illuminance evoked a decrease in activity over the anterior and ventral parts of the hypothalamus, encompassing notably the suprachiasmatic nucleus and another part of the tuberomammillary nucleus. Critically, the performance of the executive task was improved under higher illuminance and was negatively correlated with the activity of the posterior hypothalamus area. These findings reveal the distinct local dynamics of different hypothalamus regions that underlie the impact of light on cognition.

Circadian and sleep–wake homeostatic modulation of EEG activity during sleep and wakefulness

AbstractThe human sleep–wake cycle is regulated by two distinct processes: the circadian timing system (CTS) and the sleep–wake homeostatic (SWH) process. The CTS is driven by a small region in the anterior hypothalamus of the brain, which is known as the “circadian clock.” By contrast, the SWH can be conceptualized as an hourglass, whereby sleep pressure builds up during waking hours and is released during sleep. In contrast to the CTS, there is no specific brain region that controls this hourglass process. A complex modulation of these two processes affects electroencephalographic (EEG) activity throughout the 24‑h day, resulting in the emergence of specific EEG features. These features can be classified into three categories: those that show clear circadian patterns, those that are predominantly influenced by the homeostatic process, and those that show a combination of both. This review describes the EEG features quantified by spectral analysis during sleep and wakefulness derived from specific human study protocols, which enable the separation of the influence of the circadian clock and the sleep–wake hourglass process. Second, the potential for circadian and SWH modulation to influence interictal activity and seizure occurrence will be discussed, along with its implications for the diagnosis, treatment, and seizure prediction and prevention.

Age, sex, and cell type-resolved hypothalamic gene expression across the pubertal transition in mice

BackgroundThe hypothalamus plays a central role in regulating puberty. However, our knowledge of the postnatal gene regulatory networks that control the pubertal transition in males and females is incomplete. Here, we investigate the age-, sex- and cell-type-specific gene regulation in the hypothalamus across the pubertal transition.MethodsWe used RNA-seq to profile hypothalamic gene expression in male and female mice at five time points spanning the onset of puberty (postnatal days (PD) 12, 22, 27, 32, and 37). By combining this data with hypothalamic single nuclei RNA-seq data from pre- and postpubertal mice, we assigned gene expression changes to their most likely cell types of origin. In our colony, pubertal onset occurs earlier in male mice, allowing us to focus on genes whose expression is dynamic across ages and offset between sexes, and to explore the bases of sex effects.ResultsOur age-by-sex pattern of expression enriched for biological pathways involved hormone production, neuronal activation, and glial maturation. Additionally, we inferred a robust expansion of oligodendrocytes precursor cells into mature oligodendrocytes spanning the prepubertal (PD12) to peri-pubertal (PD27) timepoints. Using spatial transcriptomic data from postpubertal mice, we observed the lateral hypothalamic area and zona incerta were the most oligodendrocyte-rich regions and that these cells expressed genes known to be involved in pubertal regulation.ConclusionTogether, by incorporating multiple biological timepoints and using sex as a variable, we identified gene and cell-type changes that may participate in orchestrating the pubertal transition and provided a resource for future studies of postnatal hypothalamic gene regulation.

Auditory pallial regulation of the social behavior network

Sensory cues such as vocalizations contain important social information. Processing social features of vocalizations (e.g., vocalizer identity, emotional state) necessitates unpacking the complex sound streams in song or speech; this depends on circuits in pallial cortex. But whether and how this information is then transferred to limbic and hypothalamic regions remains a mystery. Here, using gregarious, vocal songbirds (female Zebra finches), we identify a prominent influence of the auditory pallium on one specific node of the Social Behavior Network, the lateral ventromedial nucleus of the hypothalamus (VMHl). Electrophysiological recordings revealed that social and non-social auditory stimuli elicited stimulus-specific spike trains that permitted stimulus differentiation in a large majority of VMHl single units, while transient disruption of auditory pallium elevated immediate early gene activity in VMHl. Descending functional connections such as these may be critical for the range of vertebrate species that rely on nuanced communication signals to guide social decision-making.

Isolated intracranial myeloid sarcoma as an acute myeloid leukemia relapse: A case report

Abstract Introduction/Objective Adequate assessment during intraoperative consultation on a patient with a brain mass is imperative to provide critical information that will direct the therapeutic approach during surgery. Methods/Case Report The patient is a 67-year-old female with acute myeloid leukemia (AML) on maintenance therapy and in remission for the past 2 years that developed altered mental status and seizures. Imaging revealed a diffuse intra-axial mass within the corpus callosum and right hypothalamic region. A brain stereotactic biopsy was performed. Blood work showed mild leukopenia (3.63x109/L), thrombocytopenia (platelet count of 82x109/L), and an essential normal hemoglobin level of 11.9 g/dL. A frozen section assessment during intraoperative consultation revealed an infiltration of small blue cells, suggesting a hematolymphoid process. Further histological assessment showed small to intermediate-sized monomorphic cells in sheets and around the vessels with open fine chromatin, prominent nuclei, and scant cytoplasm admixed with tingible body macrophages. Differential diagnoses included high- grade B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma blastoid variant, lymphoblastic lymphoma, and myeloid sarcoma (MS). The tumor cells were positive for CD34, CD43, and MPO (subset) and negative for CD20, PAX5, TdT, CD3, and AE1/AE3 by immunohistochemical staining, consistent with MS. Concurrent bone marrow biopsy with flow cytometric evaluation showed progressive trilineage hematopoiesis without evidence of residual leukemia. Results (if a Case Study enter NA) NA Conclusion Intracranial MS is extremely rare, and literature reviews are limited to primarily case reports. MS can occur before, during, or after the initial presentation of AML. Interestingly, this patient had an isolated intracranial myeloid sarcoma as an AML relapse without bone marrow involvement. We aim to increase the awareness of isolated recurrence of AML in the form of an intracranial MS; this disease warrants consideration in patients with a history of a myeloid neoplasm who present with neurological symptoms despite the absence of peripheral disease.

Clinical characteristics and management of adipsic arginine vasopressin deficiency in children and adolescents with sellar germ cell tumors.

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known •Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. •There are few reports on aAVP-D, most of which focus on adult patients. •The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New •Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. •Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. •Early recognition and structured management of ADI lowered the risk of complications.

18F]FDG Brain Imaging Assessment in Preclinical Acute and Chronic Stress Models Using Statistical Parametric Mapping

Previous studies have used [18F]FDG as a biomarker for depression, anxiety, or chronic stress in cancer patients1,2. However, they lack specific brain patterns and assessment in preclinical models, limiting their translational potential. Hence, we set out to establish preclinical [18F]FDG brain PET as a method to evaluate stress in vivo. Lean C57BL/6J mice were exposed to acute and chronic cooling, restraint, and surgical stress. Obese mice were on a high-fat diet for eight weeks and exposed to cooling and restraint stress. [18F]FDG was injected into fasted animals under brief isoflurane anesthesia via the tail vein. Following a 60-minute distribution phase during acute stress or one day after stress exposure (chronic), animals underwent static μPET/CT scans (Siemens® Inveon). Brain images were spatially normalized, and intensity normalization was performed using proportional and histogram-based scaling3 with PMOD (V. 3.8). Normalized images were analyzed using a brain atlas (M. Mirrione) to extract regional SUV and statistical parametric mapping (SPM12) for voxel-wise comparison. Overall, in lean mice, total brain [18F]FDG-uptake was significantly reduced across all stress models except for acute restraint, whereas total uptake was unaffected in obese mice. Subsequent brain atlas analysis of lean mice revealed changes in regional uptake for all stressors except for chronic cooling, while obese mice were affected by only acute and chronic restraint. Using SPM, we validated stress-specific hypo- and hypermetabolic areas in the brains of lean mice upon acute cooling, acute and chronic restraint, and surgery and in obese mice after chronic restraint (see Figure). We also identified overlapping areas in the brain stem and hypothalamus region following acute cooling and surgery, possibly due to post-surgical hypothermia. Our findings show that static [18F]FDG-imaging is a valuable tool for noninvasively assessing brain activity in a multitude of stress models and a suitable translational tool for stress research in mice. Please click on the 'PDF' for the full abstract!

6520 Stimulated Copeptin Measurement in the Evaluation of a Patient Presenting Hypernatremia and Adipsia

Abstract Disclosure: B.R. Assunção: None. M.M. Freire: None. M. De Castro: None. A.C. Moreira: None. P.C. Elias: None. Introduction: Hypernatremia (hyperNA) in patients submitted to neurosurgery involving the hypothalamic region prompts the diagnosis of vasopressin deficiency (AVP-D), typically accompanied by increased thirst, polydipsia and polyuria. Classic adipsic AVP-D is characterized by hypotonic polyuria and no thirst in response to hyperNA. Clinical Case: A 21 yo male patient, followed since he had a surgery for a pilocytic astrocytoma of the third ventricle at 12 yo, presented hyperNA (154 mEq/L) with mild dehydration. He denied increased thirst, polyuria or polydipsia. Further evaluation showed elevated plasma and urinary osmolalities (pOsm: 317 mOsm/Kg; uOsm: 878 mOsm/Kg). The patient was admitted for hydration and fluid balance. Oral water intake (2500-3000L/day) was prescribed. Serum sodium (Na+) decreased from 158 to 133 mEq/L within 72h, and no polyuria was detected at hyper or normonatremic states. A 3% saline infusion test (SIT) was performed with thirst visual scale and plasma copeptin (CP) assessment. Na+ rose from 139 to 150 mEq/L and pOsm from 295 to 321 mOsm/kg, with no rise in thirst scale (4,2 to 4,8 cm). Basal and maximal 3% SIT CP levels were 3.1 and 3.2 pmol/L, respectively, also displaying subnormal values. CP assessed under hypovolemic hyperNA (Na+: 158 mEq/L) was 4.1 pmol/L, suggesting that this patient might have an adispic disorder with subnormal thirst and AVP osmotic responses, explaining the lack of polyuria. Patient was treated with fixed daily fluid intake with a last follow-up Na+ of 141 mEq/L.Discussion: Adipsic AVP-D is characterized by hypotonic polyuria and no thirst in response to hyperNA. However, polyuria, a hallmark of clinical presentation, was not observed in the present case. Other adipsic disorders include upward resetting of the osmotic thresholds for both thirst and AVP release (Type A); sub-normal thirst and AVP responses to osmotic stimuli (Type B); and intact osmoregulation of AVP release with absent thirst response (Type D). The lack of polyuria even in normovolemic conditions and the subnormal thirst and CP responses to normovolemic hyperNA and dehydrate states suggest the present case to be a Type B adipsic disorder. In those patients, the secretion of small amounts of AVP in response to osmotic stimulation explains why they retain the ability to concentrate urine, limiting free water excretion. Treatment is based on a fixed fluid intake of around 2 liters per day. Conclusions: Adipsic AVP-D and other adipsic disorders are extremely rare, presenting a great challenge in the diagnosis and management. To our knowledge, this is the first description of CP assessment in a patient with hyperNA and adipsia. CP might be an important diagnostic approach to adipsic disorders. Presentation: 6/2/2024

SpaGRA: Graph augmentation facilitates domain identification for spatially resolved transcriptomics

Recent advances in spatially resolved transcriptomics (SRT) have provided new opportunities for characterizing spatial structures of various tissues. Graph-based geometric deep learning have gained widespread adoption for spatial domain identification tasks. Currently, most methods define adjacency relation between cells or spots by their spatial distance in SRT data, which overlooks key biological interactions like gene expression similarities, and leads to inaccuracies in spatial domain identification. To tackle this challenge, we propose a novel method, SpaGRA (https://github.com/sunxue-yy/SpaGRA), for automatic multi-relationship construction based on graph augmentation. SpaGRA uses spatial distance as prior knowledge and dynamically adjusts edge weights with multi-head graph attention networks (GATs). This helps SpaGRA to uncover diverse node relationships and enhance message passing in geometric contrastive learning. Additionally, SpaGRA uses these multi-view relationships to construct negative samples, addressing sampling bias posed by random selection. Experimental results show that SpaGRA demonstrates superior domain identification performance on multiple datasets generated from different protocols. Using SpaGRA, we analyzed the functional regions in the mouse hypothalamus, identified key genes related to heart development in mouse embryos, and observed cancer-associated fibroblasts enveloping cancer cells in the latest Visium HD data. Overall, SpaGRA can effectively characterize spatial structures across diverse SRT datasets.

Chronic olanzapine treatment leads to increased opioid receptor expression and changes in feeding regulating neurons in the female rat hypothalamus

Opioid receptor antagonists have shown increasing promise as an adjunct therapy to psychotropic medication. The goal is to reduce the weight gain and metabolic adverse effects that are associated with certain second-generation antipsychotics, such as olanzapine and clozapine. In this study, female rats were treated for 4 weeks with a long-acting injectable formulation of olanzapine to assess effects on hypothalamic feeding regulation. Using quantitative spatial in situ hybridization and receptor autoradiography, expression levels of the mu, kappa and delta opioid receptors were defined in the five hypothalamic areas: paraventricular nucleus (PVN), arcuate nucleus (ARC), ventromedial nucleus (VMN), dorsomedial nucleus (DMN) and lateral hypothalamus (LH). In addition, hypothalamic neuron number and size were estimated using the unbiased optical fractionator and spatial rotator methods. Hyperphagia was observed after only 24hours of olanzapine treatment, with continued weight gain throughout the duration of the study. In contrast, the observed food intake reversed to control levels after 2 weeks of olanzapine treatment. Chronic olanzapine treatment increased expression of kappa opioid receptor mRNA and receptor availability in the PVN, as well as increased mu opioid receptor availability in the PVN, ARC and VMN. These changes were accompanied by fewer anorexigenic proopiomelanocortin-expressing neurons of the ARC and corticotropin-releasing hormone expressing neurons of the PVN. This study links olanzapine-driven metabolic effects to increased opioid receptor expression in the hypothalamus, thus providing a rationale for the positive effects of using opioid receptor antagonists to relieve olanzapine adverse effects.

Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus

The lateral hypothalamic region (LH) has been identified as a key region for arousal regulation, yet the specific cell types and underlying mechanisms are not fully understood. While neurons expressing orexins (OX) are considered the primary wake-promoting population in the LH, their loss does not reduce daily wake levels, suggesting the presence of additional wake-promoting populations. In this regard, we recently discovered that a non-OX cell group in the LH, marked by the expression of neurotensin (Nts), could powerfully drive wakefulness. Activation of these NtsLH neurons elicits rapid arousal from non-rapid eye movement (NREM) sleep and produces uninterrupted wakefulness for several hours in mice. However, it remains unknown if these neurons are necessary for spontaneous wakefulness and what their precise role is in the initiation and maintenance of this state. To address these questions, we first examined the activity dynamics of the NtsLH population across sleep-wake behavior using fiber photometry. We find that NtsLH neurons are more active during wakefulness, and their activity increases concurrently with, but does not precede, wake-onset. We then selectively destroyed the NtsLH neurons using a diphtheria-toxin-based conditional ablation method, which significantly reduced wake amounts and mean duration of wake bouts and increased the EEG delta power during wakefulness. These findings demonstrate a crucial role for NtsLH neurons in maintaining normal arousal levels, and their loss may be associated with chronic sleepiness in mice.

Hypothalamus Connectivity in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling illness of unknown etiology. Increasing evidence suggests hypothalamic involvement in ME/CFS pathophysiology, which has rarely been explored using magnetic resonance imaging (MRI)in the condition. This work aimed to use MRI to examine hypothalamus connectivity in adolescents with ME/CFS and explore how this relates to fatigue severity and illness duration. 25 adolescents with ME/CFS and 23 healthy controls completed a neuroimaging protocol consisting of structural and multishell diffusion-weighted imaging sequences, in addition to the PedsQL Multidimensional Fatigue Scale to assess fatigue severity. Information about illness duration was acquired at diagnosis. Preprocessing and streamlines tractography was performed using QSIPrep combined with a custom parcellation scheme to create structural networks. The number (degree) and weight (strength) of connections between lateralized hypothalamus regions and cortical and subcortical nodes were extracted, and relationships between connectivity measures, fatigue severity, and illness duration were performed using Bayesian regression models. We observed weak-to-moderate evidence of increased degree, but not strength, of connections from the bilateral anterior-inferior (left: pd [%] = 99.18, median [95% CI] = -22.68[-40.96 to 4.45]; right: pd [%] = 99.86, median [95% CI] = -23.35[-38.47 to 8.20]), left anterior-superior (pd [%] = 99.33, median [95% CI] = -18.83[-33.45 to 4.07]) and total left hypothalamus (pd [%] = 99.44, median [95% CI] = -47.18[-83.74 to 11.03]) in the ME/CFS group compared with controls. Conversely, bilateral posterior hypothalamus degree decreased with increasing ME/CFS illness duration (left: pd [%] = 98.13, median [95% CI]: -0.47[-0.89 to 0.03]; right: pd [%] = 98.50, median [95% CI]:-0.43[-0.82 to 0.05]). Finally, a weak relationship between right intermediate hypothalamus connectivity strength and fatigue severity was identified in the ME/CFS group (pd [%] = 99.35, median [95% CI] = -0.28[-0.51 to 0.06]), which was absent in controls. These findings suggest changes in hypothalamus connectivity may occur in adolescents with ME/CFS, warranting further investigation.

Estrogen-dependent oxytocin expression in the hypothalamus and estrogen-dependent vasopressin in the median eminence.

The posterior pituitary (PP) hormones oxytocin (OXT) and arginine vasopressin (AVP) are synthesized within the hypothalamic nucleus and released from the PP into systemic circulation. Hypothalamic AVP projects its axons into the external layer of median eminence (eME) and regulates anterior pituitary hormone secretion during stress responses. Although similar as PP hormones, we demonstrate distinct regulatory roles of estrogen in hypothalamic OXT and AVP dynamics. OXT dynamics in the hypothalamus exhibit sex-dependent variations and that estrogen may influence dynamic OXT level changes, as observed in OXT-mRFP1 transgenic rats. Estrogen was also observed to modulate dynamic changes in AVP levels in the axon terminals of eME in female AVP-eGFP transgenic rats. Although OXT and AVP are produced within the similar hypothalamic region, both exhibit distinct dynamics within the hypothalamus. Estrogen acts on the hypothalamus, and further effects of estrogen replacement therapy can be expected.

Hypothalamic Gliosis is Associated With Multiple Cardiovascular Disease Risk Factors.

Hypothalamic gliosis is mechanistically linked to obesity and insulin resistance in rodent models. We tested cross-sectional associations between radiologic measures of hypothalamic gliosis in humans and clinically relevant cardiovascular disease risk factors, as well as prevalent coronary heart disease. Using brain MRI images from Framingham Heart Study participants (N=867; mean age, 55 years; 55% females), T2 signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in the amygdala (AMY) and putamen (PUT). T2 signal ratios were created in which greater relative T2 signal intensity suggests gliosis. The primary measure compared MBH to AMY (MBH/AMY); a positive control ratio (MBH/PUT) also assessed MBH whereas a negative control (PUT/AMY) did not. Outcomes were BMI, HDL-C, LDL-C, fasting triglycerides, and the presence of hypertension (n=449), diabetes mellitus (n=66), metabolic syndrome (n=254), or coronary heart disease (n=25). Dietary risk factors for gliosis were assessed in a prospective analysis. Statistical testing was performed using linear or logistic regression. Greater MBH/AMY T2 signal ratios were associated with higher BMI (β = 21.5 [95% CI, 15.4-27.6]; P<0.001), higher fasting triglycerides (β = 1.1 [95% CI, 0.6-1.7]; P<0.001), lower HDL-C (β = -20.8 [95% CI, -40.0 to -1.6]; P=0.034), and presence of hypertension (odds ratio, 1.2 [95% CI, 1.1-1.4]; P=0.0088), and the latter two were independent of BMI. Findings for diabetes mellitus were mixed and attenuated by adjusting for BMI. Metabolic syndrome was associated with MBH/AMY T2 signal ratios (odds ratio, 1.3 [95% CI, 1.1-1.6]; P<0.001). Model results were almost uniformly confirmed by the positive control ratios, whereas negative control ratios that did not test the MBH were unrelated to any outcomes (all P≥0.05). T2 signal ratios were not associated with prevalent coronary heart disease (all P>0.05), but confidence intervals were wide. Self-reported percentages of macronutrient intake were not consistently related to future T2 signal ratios. Using a well-established study of cardiovascular disease development, we found evidence linking hypothalamic gliosis to multiple cardiovascular disease risk factors, even independent of adiposity. Our results highlight the need to consider neurologic mechanisms to understand and improve cardiometabolic health.

The Transcriptome Characterization of the Hypothalamus and the Identification of Key Genes during Sexual Maturation in Goats.

Sexual maturation in goats is a dynamic process regulated precisely by the hypothalamic-pituitary-gonadal axis and is essential for reproduction. The hypothalamus plays a crucial role in this process and is the control center of the reproductive activity. It is significant to study the molecular mechanisms in the hypothalamus regulating sexual maturation in goats. We analyzed the serum hormone profiles and hypothalamic mRNA expression profiles of female goats during sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). The results indicated that from D1 to M6, serum hormone levels, including FSH, LH, progesterone, estradiol, IGF1, and leptin, exhibited an initial increase followed by a decline, peaking at M4. Furthermore, we identified a total of 508 differentially expressed genes in the hypothalamus, with a total of four distinct expression patterns. Nuclear receptor subfamily 1, group D, member 1 (NR1D1), glucagon-like peptide 1 receptor (GLP1R), and gonadotropin-releasing hormone 1 (GnRH-1) may contribute to hormone secretion, energy metabolism, and signal transduction during goat sexual maturation via circadian rhythm regulation, ECM receptor interactions, neuroactive ligand-receptor interactions, and Wnt signaling pathways. This investigation offers novel insights into the molecular mechanisms governing the hypothalamic regulation of goat sexual maturation.

Eje hipotálamo-hipofisario. Regulación neurohormonal, implicaciones patológicas, pruebas funcionales hipofisarias, indicaciones e interpretación

The hypothalamic-pituitary axis is a crucial system for maintaining homeostasis by integrating hormonal and neuronal inputs and outputs. Almost all bodily functions are regulated directly or indirectly by this axis. The hypothalamus, a small but vital brain region, monitors various inputs and maintains physiological set points through hormonal secretion, coordinating with the pituitary gland. This regulation involves multiple feedback mechanisms and interactions with other brain areas.The hypothalamus is anatomically divided into several regions and nuclei, each with specific functions. It produces a variety of hormones, including growth hormone-releasing hormone, corticotropin-releasing hormone, thyrotropin-releasing hormone, and gonadotropin-releasing hormone. These hormones regulate the secretion of corresponding hormones from the anterior pituitary gland, which control several physiological processes, including growth, metabolism, reproduction, and stress response.Pathological implications of hypothalamic-pituitary axis dysfunctions include endocrine disorders such as hyperprolactinemia, growth hormone deficiency, and hypogonadism. In addition, hypothalamic damage can lead to neurological and behavioral problems such as sleep disturbances and thermoregulation.

High-resolution segmentations of the hypothalamus and its subregions for training of segmentation models

Segmentation of brain structures on magnetic resonance imaging (MRI) is a highly relevant neuroimaging topic, as it is a prerequisite for different analyses such as volumetry or shape analysis. Automated segmentation facilitates the study of brain structures in larger cohorts when compared with manual segmentation, which is time-consuming. However, the development of most automated methods relies on large and manually annotated datasets, which limits the generalizability of these methods. Recently, new techniques using synthetic images have emerged, reducing the need for manual annotation. Here we provide a dataset composed of label maps built from publicly available ultra-high resolution ex vivo MRI from 10 whole hemispheres, which can be used to develop segmentation methods using synthetic data. The label maps are obtained with a combination of manual labels for the hypothalamic regions and automated segmentations for the rest of the brain, and mirrored to simulate entire brains. We also provide the pre-processed ex vivo scans, as this dataset can support future projects to include other structures after these are manually segmented.

Altered brain activity associated with premature ejaculation improved by electroacupuncture in rats.

Premature ejaculation (PE) is linked with abnormal brain activity that is modifiable by electroacupuncture (EA). In this study we aimed to explore the central pathological mechanism underlying EA in treating PE. Six-week-old male Sprague-Dawley rats were divided into a PE group (n = 8) and a control group (n = 8) according to ejaculatory frequency during copulatory behavior. All rats underwent EA at the Zusanli acupoint (ST-36) for 4weeks. Magnetic resonance imaging data were collected before and after EA. The behavioral parameters, plasma norepinephrine levels, fractional amplitude of low frequency fluctuation (fALFF), and regional homogeneity (ReHo) were evaluated. The PE group ejaculated more times with shorter latency compared with controls. After EA, the ejaculation frequency of the PE group decreased, and the ejaculation latency period increased, with no changes observed in the control group. Norepinephrine levels were higher in the PE group than in the controls and were positively correlated with ejaculation frequency and negatively correlated with ejaculation latency. The PE group showed lower fALFF in the right striatum and higher ReHo in the brainstem compared with controls. After EA, controls showed decreased fALFF in the right striatum, left olfactory bulb, and dorsal fornix and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, prelimbic system, right basal forebrain region, septal region, and olfactory bulb, while the model group exhibited increased fALFF in the right hypothalamic region, decreased fALFF in the left globus pallidum and right basal forebrain region and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, olfactory bulb, basal forebrain region, dentate gyrus, right dysgranular insular cortex, and striatum. Compared with the controls after EA, the model group showed increased ReHo of the right hypothalamic region and decreased ReHo of the right dysgranular insular cortex. These findings might enhance the understanding of PE and contribute to new, targeted therapies for PE. The therapeutic effects might be achieved by EA inhibiting the activity in brain regions involved in ejaculatory behavior. However, the curative effect of acupuncture might be underestimated due to some curative effects of sham acupuncture used in the control group. In conclusion, the ejaculatory frequency of rats may be reduced and ejaculation latency could be extended by EA at ST-36, which might be achieved by the effects of this treatment on brain activity.