Search Results (21)

The significant correlation between ancient medicinal practices and brain function marks a revolutionary frontier in the field of neuroscience. Acupuncture, a traditional oriental medicine, can affect brain regions, such as the hypothalamus, anterior cingulate, posterior cingulate, and hippocampus, and produces specific therapeutic effects, such as pain relief, suppression of hypertension, and alleviation of drug addiction. Among the brain regions, the hypothalamus, a small yet critical region in the brain, plays a pivotal role in maintaining homeostasis by regulating a wide array of physiological processes, including stress responses, energy balance, and pain modulation. Emerging evidence suggests that acupuncture may exert its therapeutic effects by modulating the activity of the hypothalamus and its associated neural circuits, particularly in relation to pain, stress, and metabolic regulation. Thus, we conducted a comprehensive review of past and current research on the role of the hypothalamus in mediating the therapeutic effects of acupuncture. Full article

We previously described the circadian variation and bilateral distribution of pyroglutamate aminopeptidase I (pGluPI) activity levels in photoneuroendocrine locations of adult male rats during a standard 12:12 h light–dark cycle. However, the correlational analysis between such locations has not yet been studied. This may provide new data about the unilateral and bilateral functional interaction between photoneuroendocrine locations under light and dark conditions. We analyzed the correlations between locations of a photoneuroendocrine circuit consisting of retina, anterior hypothalamus, superior cervical ganglion, and pineal gland, as well as other related photoneuroendocrine locations: posterior hypothalamus, anterior pituitary, posterior pituitary, occipital cortex, and serum. In particular, we analyzed the correlations between the left retina or the right retina versus the rest of the locations, as well as the correlations between the left and right sides of paired structures at the different time points selected from 12 h light and 12 h dark periods. Also, the profiles of correlational results were compared with the corresponding mean levels. The results demonstrate the complexity of asymmetrical brain behavior. The correlation profile did not always parallel the profile observed with the mean activity values. The diurnal behavior of correlations with the left or right retina differed from one location to another. Likewise, the diurnal variation of correlations between the left and right sides of the paired structures differed between them. Particularly, while most correlations between the left versus right sides of paired structures showed positive values, that of the posterior hypothalamus showed a negative value at 13 h of light period. In addition, except the posterior hypothalamus, most paired locations only correlated significantly with right retina at 07 h of the light period. The results demonstrate the dynamic complexity of brain asymmetry, which represents a challenge for understanding its functional meaning. Full article

Background: While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods: A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72. A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results: Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72-positive ALS patients. Conclusions: Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype. Full article

The colloid cyst is a non-malignant tumor growth made of a gelatinous material covered by a membrane of epithelial tissue. It is usually located posterior to the foramen of Monro, in the anterior aspect of the third ventricle of the brain. Due to its location, it can cause obstructive hydrocephalus, increased intracranial pressure, and sudden cardiac death, catecholamine-mediated, through hypothalamus compression. All the mechanisms are still controversial, but the role of catecholamine has been confirmed with histological findings that highlighted myocardial injury (coagulative myocytolysis and contraction band necrosis, CBN). This study presents a case of sudden death in a previously healthy 22-year-old male due to a colloid cyst of the third ventricle. A complete autopsy was performed, highlighting in the brain an abundant quantity of cerebrospinal fluid (CSF) and a 2 cm pale grayish-green rounded cyst formation partially filling and distending the third ventricle. The diagnosis was confirmed through immunohistochemical investigation: positivity for Periodic acid-Schiff (PAS) staining and CK7 expression. In cases such as the one reported here, a combined approach of autopsy, histology, and immunohistochemistry is mandatory in order to identify the neoformation’s location and morpho-structural characteristics for a correct differential diagnosis, as well as to identify the cause of death. Full article

Glucocorticoid receptor α (GRα), a ligand-regulated transcription factor, mainly activated by cortisol in humans and fish, mediates neural allostatic and homeostatic functions induced by different types of acute and chronic stress, and systemic inflammation. Zebrafish GRα is suggested to have multiple transcriptional effects essential for normal development and survival, similarly to mammals. While sequence alignments of human, monkey, rat, and mouse GRs have shown many GRα isoforms, we questioned the protein expression profile of GRα in the adult zebrafish (Danio rerio) brain using an alternative model for stress-related neuropsychiatric research, by means of Western blot, immunohistochemistry and double immunofluorescence. Our results identified four main GRα-like immunoreactive bands (95 kDa, 60 kDa, 45 kDa and 35 kDa), with the 95 kDa protein showing highest expression in forebrain compared to midbrain and hindbrain. GRα showed a wide distribution throughout the antero-posterior zebrafish brain axis, with the most prominent labeling within the telencephalon, preoptic, hypothalamus, midbrain, brain stem, central grey, locus coeruleus and cerebellum. Double immunofluorescence revealed that GRα is coexpressed in TH+, β₂-AR+ and vGLUT+ neurons, suggesting the potential of GRα influences on adrenergic and glutamatergic transmission. Moreover, GRα was co-localized in midline astroglial cells (GFAP+) within the telencephalon, hypothalamus and hindbrain. Interestingly, GRα expression was evident in the brain regions involved in adaptive stress responses, social behavior, and sensory and motor integration, supporting the evolutionarily conserved features of glucocorticoid receptors in the zebrafish brain. Full article

Studies in zebrafish and rats show that embryonic ethanol exposure at low-moderate concentrations stimulates hypothalamic neurons expressing hypocretin/orexin (Hcrt) that promote alcohol consumption, effects possibly involving the chemokine Cxcl12 and its receptor Cxcr4. Our recent studies in zebrafish of Hcrt neurons in the anterior hypothalamus (AH) demonstrate that ethanol exposure has anatomically specific effects on Hcrt subpopulations, increasing their number in the anterior AH (aAH) but not posterior AH (pAH), and causes the most anterior aAH neurons to become ectopically expressed further anterior in the preoptic area (POA). Using tools of genetic overexpression and knockdown, our goal here was to determine whether Cxcl12a has an important function in mediating the specific effects of ethanol on these Hcrt subpopulations and their projections. The results demonstrate that the overexpression of Cxcl12a has stimulatory effects similar to ethanol on the number of aAH and ectopic POA Hcrt neurons and the long anterior projections from ectopic POA neurons and posterior projections from pAH neurons. They also demonstrate that knockdown of Cxcl12a blocks these effects of ethanol on the Hcrt subpopulations and projections, providing evidence supporting a direct role of this specific chemokine in mediating ethanol’s stimulatory effects on embryonic development of the Hcrt system. Full article

Background: Endoscopic third ventriculostomy (ETV) is an effective treatment for hydrocephalus. The in-depth understanding of microanatomy is essential for accurate diagnosis, treatment and complications prevention. The aim of this study is to supplement the knowledge gap regarding the microanatomical metrics and correlations for which the literature includes only scarce mentions at best. Methods: This is a descriptive microanatomical study including 25 cadaver brains. Specimens from donors with neurological, psychiatric disorders or alcohol abuse were excluded. Surgical loops were used for harvesting. High-precision tools were employed to dissect and measure the anatomical landmarks under a surgical microscope. Each measurement was performed in three consecutive attempts and outliers were rejected. RStudio was used for statistical analysis. Distribution was evaluated employing the Shapiro–Wilk test. Normally distributed values were presented as mean and standard deviation, and others as median and interquartile range. Results: The age of the donors was 61.72 (±10.08) years. The distance from the anterior aspect of the foramen of Monro to the anterior margin of the mamillary body was 16.83 (±1.04) mm, and to the posterior margin was 16.76 (±1.9) mm. The distance from the anterior mamillary body margin to the infundibulum was 6.39 (±1.9) mm, to the optic recess was 8.25 (±1.84) mm, and to the apex of the vertebral artery was 5.05 (±1.62) mm. The distance from the anterior commissure to the brain aqueduct was 22.46 (±2.29) mm, and to the infundibulum was 13.93 (±2.54) mm. The mamillary body diameter was 4.91 (±0.34) mm in the anteroposterior and 4.21 (±0.48) mm in the cranio-caudal plane. The intraventricular segment was protruding by 1.63 (±0.46) mm. The diameter of the hypothalamus on the anterior margin of mamillary bodies was 1.37 (±0.75) mm, of the Liliequist membrane was 0.19 (±0.07) mm and of the lamina terminalis was 0.35 (±0.32) mm. Conclusion: The presented microanatomical measurements and correlations are expected to contribute to the improvement of ETV safety. Full article

Craniopharyngioma (CP) is a histologically benign tumor with high mortality and morbidity. Although surgical treatment is essential in managing CP, the best surgical approach is debated. A retrospective cohort of 117 patients with adult-onset CP (AOCP) treated between 2018 and 2020 in Beijing Tiantan Hospital was identified and examined. The effects of traditional craniotomy (TC) and endoscopic endonasal transsphenoidal surgery (EETS) on the extent of surgical resection, hypothalamic involvement (HI), postoperative endocrine function, and postoperative weight were compared in the cohort. The cohort comprised 43 males and 74 females, divided into the TC (n = 59) and EETS (n = 58) groups. The EETS group possessed a higher rate of gross total resection (GTR) (adjusted odds ratio (aOR) = 4.08, p = 0.029) and improved HI (aOR = 2.58, p = 0.041) than the TC group. Worse postoperative HI was only observed in the TC group (5 patients). The EETS was associated with fewer adverse hormonal outcomes, including posterior pituitary dysfunction (aOR = 0.386, p = 0.040) and hypopituitarism (aOR = 0.384, p = 0.031). Additionally, multivariate logistic regression analysis confirmed that EETS was related to fewer cases of weight gain >5% (aOR = 0.376, p = 0.034), significant weight change (aOR = 0.379, p = 0.022), and postoperative obesity (aOR = 0.259, p = 0.032). Compared to TC, EETS shows advantages in accomplishing GTR, hypothalamus protection, postoperative endocrine function reservation, and postoperative weight control. These data suggest that the EETS deserves more application in managing patients with AOCP. Full article

Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this solute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin–angiotensin–aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis. Full article

The role of the hypothalamus and the limbic system at the onset of a migraine attack has recently received significant interest. We analyzed diffusion tensor imaging (DTI) parameters of the entire hypothalamus and its subregions in 15 patients during a spontaneous migraine attack and in 20 control subjects. We also estimated the non-linear measure resting-state functional MRI BOLD signal’s complexity using Higuchi fractal dimension (FD) and correlated DTI/fMRI findings with patients’ clinical characteristics. In comparison with healthy controls, patients had significantly altered diffusivity metrics within the hypothalamus, mainly in posterior ROIs, and higher FD values in the salience network (SN). We observed a positive correlation of the hypothalamic axial diffusivity with migraine severity and FD of SN. DTI metrics of bilateral anterior hypothalamus positively correlated with the mean attack duration. Our results show plastic structural changes in the hypothalamus related to the attacks severity and the functional connectivity of the SN involved in the multidimensional neurocognitive processing of pain. Plastic changes to the hypothalamus may play a role in modulating the duration of the attack. Full article

Originally named for its expression in the posterior hypothalamus in rats and after the Greek word for “appetite”, hypocretin, or orexin, as it is known today, gained notoriety as a neuropeptide regulating feeding behavior, energy homeostasis, and sleep. Orexin has been proven to be involved in both central and peripheral control of neuroendocrine functions, energy balance, and metabolism. Since its discovery, its ability to increase appetite as well as regulate feeding behavior has been widely explored in mammalian food production animals such as cattle, pigs, and sheep. It is also linked to neurological disorders, leading to its intensive investigation in humans regarding narcolepsy, depression, and Alzheimer’s disease. However, in non-mammalian species, research is limited. In the case of avian species, orexin has been shown to have no central effect on feed-intake, however it was found to be involved in muscle energy metabolism and hepatic lipogenesis. This review provides current knowledge and summarizes orexin’s physiological roles in livestock and pinpoints the present lacuna to facilitate further investigations. Full article

Immune checkpoint inhibitors (ICI) prolong the survival in an increasing number of patients affected by several malignancies, but at the cost of new toxicities related to their mechanisms of action, autoimmunity. Endocrine toxicity frequently occurs in patients on ICI, but endocrine dysfunctions differ based on the ICI-subclass, as follows: agents targeting the CTLA4-receptor often induce hypophysitis and rarely thyroid dysfunction, which is the opposite for agents targeting the PD-1/PD-L1 axis. Recently, few cases of central diabetes insipidus have been reported as an adverse event induced by both ICI-subclasses, either in the context of anterior hypophysitis or as selective damage to the posterior pituitary or in the context of hypothalamitis. These new occurrences demonstrate, for the first time, that ICI-induced autoimmunity may involve any tract of the hypothalamic–pituitary axis. However, the related pathogenic mechanisms remain to be fully elucidated. Similarly, the data explaining the endocrine system susceptibility to primary and ICI-induced autoimmunity are still scarce. Since ICI clinical indications are expected to expand in the near future, ICI-induced autoimmunity to the hypothalamic–pituitary axis presents as a unique in vivo model that could help to clarify the pathogenic mechanisms underlying both the dysfunction induced by ICI to the hypothalamus–pituitary axis and primary autoimmune diseases affecting the same axis. Full article

We recently discovered a novel neuropeptide of 80 amino acid residues: neurosecretory protein GL (NPGL), in the hypothalamus of birds and rodents. NPGL is localized in the lateral posterior part of the arcuate nucleus (ArcLP), and it enhances feeding behavior and fat accumulation in mice. Various neurotransmitters, such as catecholamine, glutamate, and γ-aminobutyric acid (GABA), produced in the hypothalamus are also involved in energy metabolism. The colocalization of neurotransmitters and NPGL in neurons of the ArcLP leads to the elucidation of the regulatory mechanism of NPGL neurons. In this study, we performed double immunofluorescence staining to elucidate the relationship between NPGL and neurotransmitters in mice. The present study revealed that NPGL neurons did not co-express tyrosine hydroxylase as a marker of catecholaminergic neurons and vesicular glutamate transporter-2 as a marker of glutamatergic neurons. In contrast, NPGL neurons co-produced glutamate decarboxylase 67, a marker for GABAergic neurons. In addition, approximately 50% of NPGL neurons were identical to GABAergic neurons. These results suggest that some functions of NPGL neurons may be related to those of GABA. This study provides insights into the neural network of NPGL neurons that regulate energy homeostasis, including feeding behavior and fat accumulation. Full article

The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to produce gametes is not fully understood. Hence, we characterized kisspeptin system in rat spermatozoa and epididymis caput and cauda and analyzed the possible presence of Kiss1 in the epididymal fluid. The presence of Kiss1 and Kiss1R in spermatozoa collected from epididymis caput and cauda was evaluated by Western blot; significant high Kiss1 levels in the caput (p < 0.001 vs. cauda) and constant levels of Kiss1R proteins were observed. Immunofluorescence analysis revealed that the localization of Kiss1R in sperm head shifts from the posterior region in the epididymis caput to perforatorium in the epididymis cauda. In spermatozoa-free epididymis, Western blot revealed higher expression of Kiss1 and Kiss1R in caput (p < 0.05 vs. cauda). Moreover, immunohistochemistry revealed that Kiss1 and Kiss1R proteins were mainly localized in the secretory epithelial cell types and in contractile myoid cells, respectively. Finally, both dot blot and Elisa revealed the presence of Kiss1 in the epididymal fluid collected from epididymis cauda and caput, indicating that rat epididymis and spermatozoa possess a complete kisspeptin system. In conclusion, we reported for the first time in rodents Kiss1R trafficking in spermatozoa during the epididymis transit and Kiss1 measure in the epididymal fluid, thus suggesting a possible role for the system in spermatozoa maturation and storage within the epididymis. Full article

The pituitary is an organ of dual provenance: the anterior lobe is epithelial in origin, whereas the posterior lobe derives from the neural ectoderm. The pituitary gland is a pivotal element of the axis regulating reproductive function in mammals. It collects signals from the hypothalamus, and by secreting gonadotropins (FSH and LH) it stimulates the ovary into cyclic activity resulting in a menstrual cycle and in ovulation. Pituitary organogenesis is comprised of three main stages controlled by different signaling molecules: first, the initiation of pituitary organogenesis and subsequent formation of Rathke’s pouch; second, the migration of Rathke’s pouch cells and their proliferation; and third, lineage determination and cellular differentiation. Any disruption of this sequence, e.g., gene mutation, can lead to numerous developmental disorders. Gene mutations contributing to disordered pituitary development can themselves be classified: mutations affecting transcriptional determinants of pituitary development, mutations related to gonadotropin deficiency, mutations concerning the beta subunit of FSH and LH, and mutations in the DAX-1 gene as a cause of adrenal hypoplasia and disturbed responsiveness of the pituitary to GnRH. All these mutations lead to disruption in the hypothalamic–pituitary–ovarian axis and contribute to the development of primary amenorrhea. Full article