Hypothalamic Inflammation as a Potential Pathophysiologic Basis for the Heterogeneity of Clinical, Hormonal, and Metabolic Presentation in PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. It is a heterogeneous condition characterized by reproductive, endocrine, metabolic, and psychiatric abnormalities. More than one pathogenic mechanism is involved in its development. On the other hand, the hypothalamus plays a crucial role in many important functions of the body, including weight balance, food intake, and reproduction. A high-fat diet with a large amount of long-chain saturated fatty acids can induce inflammation in the hypothalamus. Hypothalamic neurons can sense extracellular glucose concentrations and participate, with a feedback mechanism, in the regulation of whole-body glucose homeostasis. When consumed nutrients are rich in fat and sugar, and these regulatory mechanisms can trigger inflammatory pathways resulting in hypothalamic inflammation. The latter has been correlated with metabolic diseases, obesity, and depression. In this review, we explore whether the pattern and the expansion of hypothalamic inflammation, as a result of a high-fat and -sugar diet, may contribute to the heterogeneity of the clinical, hormonal, and metabolic presentation in PCOS via pathophysiologic mechanisms affecting specific areas of the hypothalamus. These mechanisms could be potential targets for the development of effective therapies for the treatment of PCOS.

Construction of a Mex3c Gene-Deficient Mouse Model to Study C-FOS Expression in Hypothalamic Nuclei and Observe Morphological Differences in Embryonic Neural Tube Development.

BACKGROUND This study utilized CRISPR/Cas9 gene editing technology to construct a Mex3c gene-deficient mouse model, and studied C-FOS expression in hypothalamic nuclei. MATERIAL AND METHODS Thirty Mex3c-/+ mice, 30 mice in the normal group, and 30 Mex3c-/+ mice were randomly divided into control, leptin, and ghrelin groups according to different intraperitoneal injections. HE and Nissl staining were performed to observe the morphology of hypothalamic nerve cells. The C-FOS expression in hypothalamic nuclei of each group was analyzed by immunohistochemical techniques. HE staining was used to observe neural tube morphology, and LFB staining was used to observe nerve myelin sheath morphology. TEM was used to observe neuronal ultrastructure and immunohistochemical techniques were utilized to analyze nestin expression. RESULTS C-FOS expression was lower in the normal control group than in the leptin and ghrelin groups. The Mex3c control group and the leptin group had higher C-FOS expression than the ghrelin group. In neural tube studies, no significant differences were found in the neural tube pathological sections of E14.5-day embryos in each group. Nestin results demonstrated lower expression in the normal group and there was little difference between the HD and Mex3c groups. CONCLUSIONS Mex3c appears to participate in the regulation of energy metabolism by inducing C-FOS expression in the hypothalamus. The neural tubes of the offspring of Mex3c-/+ mice had defects during development.

Programación fetal / Fetal programming

El término Origen Temprano de las Enfermedades del Adulto explica la aparición temprana de las condiciones anormales cardiovasculares y metabólicas en la vida adulta, mayor riesgo de morbilidad y muerte asociados a factores ambientales, especialmente nutricionales, que actúan en las primeras etapas de la vida. Estas respuestas programadas dependen de la naturaleza del estímulo o noxa, del tiempo de exposición y del momento de ocurrencia de la noxa, pudiendo un solo genotipo original varios fenotipos y estarían condicionadas por criterios críticos en los cuales se desarrollarían cambios a largo plazo pudiendo ser reversibles o no. La Programación Fetal explica que respuestas adaptativas embrionarias y fetales en un ambiente subóptimo genera consecuencias adversas permanentes. La desnutrición, así como la sobrenutrición fetal aumenta el riesgo de desarrollar alteraciones en el peso y composición corporal fetal, y posteriormente obesidad, síndrome metabólico, incremento en la adiposidad, alteración en el metabolismo de la glucosa y / o insulina, alteración del metabolismo lipídico, alteraciones hepáticas y de las cifras tensionales. La impronta genómica es esencial para el desarrollo y defectos en la misma puede originar alteraciones de la identidad parental transmisibles a las siguientes generaciones. Esta programación fetal puede ser explicada por la epigenética, definida como la serie de alteraciones hereditarias de la expresión genética a través de modificaciones del ADN y las histonas centrales sin cambios en la secuencia de ADN. Estas modificaciones epigenéticas alteran la estructura y condensación de la cromatina, afectando la expresión del genotipo y fenotipo. Este artículo desarrolla los aspectos involucrados en la Programación Fetal y los posibles mecanismos sobre la misma(AU)

The term Early Origin of Adult Diseases explains the early onset of abnormal cardiovascular and metabolic conditions in adult life, increased risk of morbidity and death associated with environmental factors, especially nutritional factors, that act in the early stages of life. These programmed responses depend on the nature of the stimulus or noxa, the time of exposure and the moment of occurrence of the noxa, with a single original genotype being able to have several phenotypes and would be conditioned by critical criteria in which long-term changes could develop, reversibles or not. Fetal Programming explains that embryonic and fetal adaptive responses in a suboptimal environment generate permanent adverse consequences. Fetal malnutrition as overnutrition increases the risk of developing alterations in fetal body weight and composition, and subsequently obesity, metabolic syndrome, increased adiposity, impaired glucose and / or insulin metabolism, impaired lipid metabolism, liver disorders and altered blood pressure. The genomic imprint is essential for development and defects in it can cause alterations of the parental identity and are transmitted to the following generations. This fetal programming can be explained by epigenetics, defined as the series of inherited alterations of genetic expression through modifications of DNA and central histones without changes in the DNA sequence. These epigenetic modifications alter the structure and condensation of chromatin, affecting the expression of the genotype and phenotype. This article develops the aspects involved in Fetal Programming and the possible mechanisms on it(AU)

The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure.

The androgen receptor (AR), oestrogen receptor alpha (ESR1) and oestrogen receptor beta (ESR2) play essential roles in mediating the effect of sex hormones on sex differences in the brain. Using Voxel-based morphometry (VBM) and gene sizing in two independent samples (discovery n â€‹= â€‹173, replication â€‹= â€‹61), we determine the common and unique influences on brain sex differences in grey (GM) and white matter (WM) volume between repeat lengths (n) of microsatellite polymorphisms AR(CAG)n, ESR1(TA)n and ESR2(CA)n. In the hypothalamus, temporal lobes, anterior cingulate cortex, posterior insula and prefrontal cortex, we find increased GM volume with increasing AR(CAG)n across sexes, decreasing ESR1(TA)n across sexes and decreasing ESR2(CA)n in females. Uniquely, AR(CAG)n was positively associated with dorsolateral prefrontal and orbitofrontal GM volume and the anterior corona radiata, left superior fronto-occipital fasciculus, thalamus and internal capsule WM volume. ESR1(TA)n was negatively associated with the left superior corona radiata, left cingulum and left inferior longitudinal fasciculus WM volume uniquely. ESR2(CA)n was negatively associated with right fusiform and posterior cingulate cortex uniquely. We thus describe the neuroanatomical correlates of three microsatellite polymorphisms of steroid hormone receptors and their relationship to sex differences.

Fiber dissection and 3-tesla diffusion tensor tractography of the superior cerebellar peduncle in the human brain: emphasize on the cerebello-hypthalamic fibers.

Experimental studies in various species using tract-tracing techniques showed clear evidence of the presence of cerebello-hypothalamic projections. However, these connections were not clearly described in humans. In the present study we aimed to describe the direct cerebello-hypothalamic connections within the superior cerebellar peduncle (SCP) using fiber dissection techniques on cadaveric brains and diffusion tensor tractography (DTI) in healthy adults. Fiber dissection was performed in a stepwise manner from lateral to medial on 6 cerebral hemispheres. The gray matter was decorticate and fiber tracts were revealed. The SCP was exposed and the fibers were traced distally using wooden spatulas. The MRI examinations were performed in seven cases using 3-tesla 3T unit. The direct cerebello-hyothalamic pathways were exposed using high-spatial-resolution DTI. The present study using both fiber dissection and DTI in adult human showed direct cerebello-hypothalamic fibers within the SCP. The SCP fibers course anterolateral to the cerebral aqueduct reaching the level of the red nucleus of the midbrain. The majority of the fibers crosses over and reached the contralateral diencephalic structures and some of these fibers terminated at the contralateral anterior hypothalamic area. Some of the uncrossed SCP fibers reached the ipsilateral diencephalic structures and terminated at the ipsilateral posterior hypothalamic area. We further reported the close relationship of the SCP with the MCP, lateral lemniscus, red nucleus and substantia nigra. In the DTI evaluations of the SCP we exposed unilateral left cerebello-hypothalamic fibers in five cases and bilateral cerebello-hypothalamic fibers in two cases. The present study demonstrates the direct cerebello-hypothalamic connections within the SCP for the first time using fiber dissection and DTI technique in the human brain. The detailed knowledge of the cerebello-hypothalamic fibers can outline the unexplained deficit that may occur during regional surgery.

Accessory mammillary bodies formed by the enlarged lateral mammillary nuclei: cytoarchitecture.

Post mortem examination of the hypothalamus of a 79-year-old woman, deceased in cardiac arrest without recorded neurological symptoms, revealed well-defined spherical protrusions located rostro-laterally to the mammillary bodies that appear to be regular size when compared to normal. Cytoarchitectonically, these accessory mammillary bodies are formed by the enlarged lateral mammillary nucleus that is normally a thin shell over the medial. The mammillary nuclei appear to function synergistically in memory formation in rats; however, the functional consequences of the present variation are difficult to interpret due to lack of human data. Most importantly, in addition to the possible functional consequences, lateral mammillary bodies can be falsely identified as various neuropathological processes of the basal diencephalon including gliomas; therefore, it is extremely important to disseminate this unique morphological variant among clinicians.

Mapping the brain of the chicken (Gallus gallus), with emphasis on the septal-hypothalamic region.

There has been remarkable progress in discoveries made in the avian brain, particularly over the past two decades. This review first highlights some of the discoveries made in the forebrain and credits the Avian Brain Nomenclature Forum, responsible for changing many of the terms found in the cerebrum and for stimulating collaborative research thereafter. The Forum facilitated communication among comparative neurobiologists by eliminating confusing and inaccurate names. The result over the past 15yearshas been a standardized use of avian forebrain terms. Nonetheless, additional changes are needed. The goal of the paper is to encourage a continuing effort to unify the nomenclature throughout the entire avian brain. To emphasize the need for consensus for a single name for each neural structure, I have selected specific structures in the septum and hypothalamus that our laboratory has been investigating, to demonstrate a lack of uniformity in names applied to conservative brain regions compared to the forebrain. The specific areas reviewed include the distributions of gonadotropin-releasing hormone neurons and their terminal fields in circumventricular organs, deep-brain photoreceptors, gonadotropin inhibitory neurons and a complex structure and function of the nucleus of the hippocampal commissure.

A Thalamo-Hypothalamic Pathway That Activates Oxytocin Neurons in Social Contexts in Female Rats.

Oxytocin is released from neurons in the paraventricular hypothalamic nucleus (PVN) in mothers upon suckling and during adult social interactions. However, neuronal pathways that activate oxytocin neurons in social contexts are not yet established. Neurons in the posterior intralaminar complex of the thalamus (PIL), which contain tuberoinfundibular peptide 39 (TIP39) and are activated by pup exposure in lactating mothers, provide a candidate projection. Innervation of oxytocin neurons by TIP39 neurons was examined by double labeling in combination with electron microscopy and retrograde tract-tracing. Potential classic neurotransmitters in TIP39 neurons were investigated by in situ hybridization histochemistry. Neurons activated after encounter with a familiar conspecific female in a familiar environment were mapped with the c-Fos technique. PVN and the supraoptic nucleus oxytocin neurons were closely apposed by an average of 2.0 and 0.4 TIP39 terminals, respectively. Asymmetric (presumed excitatory) synapses were found between TIP39 terminals and cell bodies of oxytocin neurons. In lactating rats, PIL TIP39 neurons were retrogradely labeled from the PVN. TIP39 neurons expressed vesicular glutamate transporter 2 but not glutamic acid decarboxylase 67. PIL contained a markedly increased number of c-Fos-positive neurons in response to social encounter with a familiar conspecific female. Furthermore, the PIL received ascending input from the spinal cord and the inferior colliculus. Thus, TIP39 neurons in the PIL may receive sensory input in response to social interactions and project to the PVN to innervate and excite oxytocin neurons, suggesting that the PIL-PVN projection contributes to the activation of oxytocin neurons in social contexts.

Comparative Anatomical Study on Operability in Surgical Approaches to the Anterior Part of the Third Ventricle.

BACKGROUND: Surgery of the third ventricle still represents a challenge in modern neurosurgery. To optimize the surgical planning, some aspects, related to ventricular anatomy, have to be taken into consideration. An operability score could represent a preoperative tool to evaluate these variables to choose a tailored surgical approach. METHODS: We compared the transcallosal transforaminal approach and the combined interhemispheric subcommissural translamina terminalis approach (CISTA) to the anterior part of the third ventricle, applying the operability score. RESULTS: Compared with the transcallosal transforaminal approach, the CISTA provides a statistically significant improvement in terms of depth of surgical field, surgical angle of attack, and maneuverability arc considering as 4 approach-related critical structures: the optic chiasm (P value: <0.0001, <0.0001, <0.0001, respectively), the anterior commissure (P value: <0.0001, <0.0001, <0.0001 respectively), the tuber cinereum (P value: <0.0001, 0.0224, 0.0173), and the interthalamic adhesion (P value: 0.2917, <0.0001, <0.0001 respectively). CONCLUSIONS: Tumors originating from the anterosuperior part of the third ventricle can be easily approached through a transcallosal transforaminal route, whereas lesions arising from the anteroinferior portion of the third ventricle might be safely and effectively approached through the CISTA.

Conserved Hypothalamic c-Fos Activation Pattern Induced by the mGlu5 Receptor Antagonist MPEP during Peri-pubertal Development in Mice.

INTRODUCTION: 2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a selective mGlu5 receptor (mGluR5) antagonist intensively studied as potential novel anxiolytic drug. In the adult, MPEP activates stress-related areas, including the paraventricular nucleus of the hypothalamus (PVNh). However, it is unknown if MPEP targets similar structures in the juvenile brain as well. METHODS: Here we examined by immunohistochemical methods the induction pattern of the neuronal activity marker c-Fos by MPEP at peri-pubertal stages (postnatal day P16, P24, P32 and P40) in C57BL6/N mice. RESULTS: Despite the previously reported sharply diminished hypothalamic mGluR5 expression during postnatal development, we found a highly conserved PVNh activation by MPEP together with c-Fos expression in the extended amygdala. Interestingly, MPEP also robustly activated the paraventricular nucleus of the thalamus (PVT) and suprachiasmatic nucleus (SCN), regions associated with the modulation of circadian rhythms. DISCUSSION: These results indicate a conserved activation pattern induced by MPEP in the young vs. adult brain especially in brain areas regulating stress and circadian rhythms and may be of importance regarding the effect of mGluR5 antagonists in the treatment of mood disorders during juvenile development.

Estrogen- and Satiety State-Dependent Metabolic Lateralization in the Hypothalamus of Female Rats.

Hypothalamus is the highest center and the main crossroad of numerous homeostatic regulatory pathways including reproduction and energy metabolism. Previous reports indicate that some of these functions may be driven by the synchronized but distinct functioning of the left and right hypothalamic sides. However, the nature of interplay between the hemispheres with regard to distinct hypothalamic functions is still unclear. Here we investigated the metabolic asymmetry between the left and right hypothalamic sides of ovariectomized female rats by measuring mitochondrial respiration rates, a parameter that reflects the intensity of cell and tissue metabolism. Ovariectomized (saline injected) and ovariectomized+estrogen injected animals were fed ad libitum or fasted to determine 1) the contribution of estrogen to metabolic asymmetry of hypothalamus; and 2) whether the hypothalamic asymmetry is modulated by the satiety state. Results show that estrogen-priming significantly increased both the proportion of animals with detected hypothalamic lateralization and the degree of metabolic difference between the hypothalamic sides causing a right-sided dominance during state 3 mitochondrial respiration (St3) in ad libitum fed animals. After 24 hours of fasting, lateralization in St3 values was clearly maintained; however, instead of the observed right-sided dominance that was detected in ad libitum fed animals here appeared in form of either right- or left-sidedness. In conclusion, our results revealed estrogen- and satiety state-dependent metabolic differences between the two hypothalamic hemispheres in female rats showing that the hypothalamic hemispheres drive the reproductive and satiety state related functions in an asymmetric manner.

The effect of short fasting on the hypothalamic neuronal system of kisspeptin in peripubertal female lambs.

Changes in the metabolic state induced by feed restrictions have a negative effect on the reproduction in mammals and result in the delayed puberty onset. Kisspeptin (kp) has been demonstrated as a pivotal regulator of GnRH/LH secretion during puberty. To elucidate the involvement of kp in the hypothalamic secretory function in altered metabolic state, the expression of kp protein was investigated in peripubertal female lambs after short fasting. The experiment was conducted on immature 32-weeks old Merino lambs fed standard diet (n=5) or fasted for 72h (n=5). The localization and expression of kp was evaluated using immunohistochemistry. Serum LH concentration was determined using radioimmunology. In the hypothalami of fasted sheep, the number of kp perikarya and the percent of density of neuronal kp network in the caudal part of the nucleus arcuatus were significantly less (P<0.001) than in standard fed lambs. The decrease of kp axons throughout areas extending from area preoptica to medial basal hypothalamus and in the median eminence in fasted lambs compared to standard fed ones was observed. Plasma LH concentrations and amplitude of pulses decreased (P<0.05) after 3 days of fasting compared to standard fed group. The decrease of the kp expression is likely due to diminished kp protein synthesis, and its storage in the neurons. In summary, the data are the first to demonstrate interactions between metabolic status and kp neuronal system in lambs before puberty, and suggest that kp neurons may represent a link between metabolic signals and central control of reproduction.

60 YEARS OF NEUROENDOCRINOLOGY: The structure of the neuroendocrine hypothalamus: the neuroanatomical legacy of Geoffrey Harris.

In November 1955, Geoffrey Harris published a paper based on the Christian A Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore, MD, USA. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing so, Harris introduced a set of properties that helped define the neuroendocrine hypothalamus. They included: i) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; ii) an analogy between the representation of body parts in the sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and iii) the idea that neuroendocrine neurons are motor neurons and the pituitary stalk functions as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons must pass in order to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries that were being made in the early 1950s were beginning to influence neuroendocrinology? This Thematic Review discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and, within this framework, how novel and powerful techniques are currently taking our understanding of the structure of the neuroendocrine hypothalamus to new levels.

Cerebrospinal fluid reconstitution via a perfusion-based cadaveric model: feasibility study demonstrating surgical simulation of neuroendoscopic procedures.

Cadaveric surgical simulation carries the advantage of realistic anatomy and haptic feedback but has been historically difficult to model for intraventricular approaches given the need for active flow of CSF. This feasibility study was designed to simulate intraventricular neuroendoscopic approaches and techniques by reconstituting natural CSF flow in a cadaveric model. In 10 fresh human cadavers, a simple cervical laminectomy and dural opening were made, and a 12-gauge arterial catheter was introduced. Saline was continuously perfused at physiological CSF pressures to reconstitute the subarachnoid space and ventricles. A neuroendoscope was subsequently inserted via a standard right frontal bur hole. In 8 of the 10 cadavers, adequate reconstitution and endoscopic access of the lateral and third ventricles were achieved. In 2 cadavers, ventricular access was not feasible, perhaps because of a small ventricle size and/or deteriorated tissue quality. In all 8 cadavers with successful CSF flow reconstitution and endoscopic access, identifying the foramen of Monro was possible, as was performing septum pellucidotomy and endoscopic third ventriculostomy. Furthermore, navigation of the cerebral aqueduct, fourth ventricle, prepontine cistern, and suprasellar cistern via the lamina terminalis was possible, providing a complementary educational paradigm for resident education that cannot typically be performed in live surgery. Surgical simulation plays a critical and increasingly prominent role in surgical education, particularly for techniques with steep learning curves including intraventricular neuroendoscopic procedures. This novel model provides feasible and realistic surgical simulation of neuroendoscopic intraventricular procedures and approaches.

Microsurgical anatomy of perforated arteries in the hypothalamic area.

AIM: This study aimed to investigate the microsurgical anatomy of perforating arteries in the hypothalamic area, which are associated with diabetes insipidus. MATERIAL AND METHODS: A total of 20 adult cadaver heads soaked in formalin were infused with red latex through the carotid artery and vertebral artery, and supplementary perfusion was performed after 1 day. RESULTS: The perforating arteries in the hypothalamic area could be divided into three groups according to their origins, namely, the former, below and outside groups. The former group mainly comprised the perforating arteries near the current communicating arteries. The outside group comprised the perforating arteries from the upper clinoid segment of the internal carotid and posterior communicating arteries. The below group comprised the bottom hypophyseal arteries of the cavernous segment from the internal carotid artery. CONCLUSION: Vascular injuries that occur during surgery can be minimised by understanding the distribution of the aforementioned vessels.

Combined inhibition of PI3Kß and PI3Kγ reduces fat mass by enhancing α-MSH-dependent sympathetic drive.

Obesity is defined as an abnormal increase in white adipose tissue and has become a major medical burden worldwide. Signals from the brain control not only appetite but also energy expenditure, both of which contribute to body weight. We showed that genetic or pharmacological inhibition of two phosphatidylinositol 3-kinases (PI3Kß and PI3Kγ) in mice reduced fat mass by promoting increased energy expenditure. This effect was accompanied by stimulation of lipolysis and the acquisition of the energy-burning characteristics of brown adipocytes by white adipocytes, a process referred to as "browning." The browning of the white adipocytes involved increased norepinephrine release from the sympathetic nervous system. We found that PI3Kß and PI3Kγ together promoted a negative feedback loop downstream of the melanocortin 4 receptor in the central nervous system, which controls appetite and energy expenditure in the periphery. Analysis of mice with drug-induced sympathetic denervation suggested that these kinases controlled the sympathetic drive in the brain. Administration of inhibitors of both PI3Kß and PI3Kγ to mice by intracerebroventricular delivery induced a 10% reduction in fat mass as quickly as 10 days. These results suggest that combined inhibition of PI3Kß and PI3Kγ might represent a promising treatment for obesity.

Social status and GnRH soma size in female convict cichlids (Amatitlania nigrofasciatus).

Gonadotropin-releasing hormone (GnRH) neurons in the preoptic area (POA) of the hypothalamus play a key role in regulating reproductive function. These neurons in turn are modulated by environmental influences, including the social environment. In both the Old World cichlid Astatotilapia burtoni and the New World cichlid Amatitlania nigrofasciatus, the size of the soma of GnRH expressing neurons in the POA varies with social status in males and breeding state in females. Dominant males have larger GnRH-releasing cells than subordinate males, and spawning females have larger GnRH-releasing cells than brooding females. A. nigrofasciatus is monogamous and both sexes engage in similar levels of aggression and territorial defense. Here we test whether female A. nigrofasciatus display GnRH-releasing cell plasticity as a function of dominant status. We find that GnRH-releasing neuron soma sizes are larger in dominant females and that this difference is independent of differences in gonado-somatic index in A. nigrofasciatus.

Efferent projections of the suprachiasmatic nucleus based on the distribution of vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP) immunoreactive fibers in the hypothalamus of Sapajus apella.

The suprachiasmatic nucleus (SCN), which is considered to be the master circadian clock in mammals, establishes biological rhythms of approximately 24 h that several organs exhibit. One aspect relevant to the study of the neurofunctional features of biological rhythmicity is the identification of communication pathways between the SCN and other brain areas. As a result, SCN efferent projections have been investigated in several species, including rodents and a few primates. The fibers originating from the two main intrinsic fiber subpopulations, one producing vasoactive intestinal peptide (VIP) and the other producing arginine vasopressin (AVP), exhibit morphological traits that distinguish them from fibers that originate from other brain areas. This distinction provides a parameter to study SCN efferent projections. In this study, we mapped VIP (VIP-ir) and AVP (AVP-ir) immunoreactive (ir) fibers and endings in the hypothalamus of the primate Sapajus apella via immunohistochemical and morphologic study. Regarding the fiber distribution pattern, AVP-ir and VIP-ir fibers were identified in regions of the tuberal hypothalamic area, retrochiasmatic area, lateral hypothalamic area, and anterior hypothalamic area. VIP-ir and AVP-ir fibers coexisted in several hypothalamic areas; however, AVP-ir fibers were predominant over VIP-ir fibers in the posterior hypothalamus and medial periventricular area. This distribution pattern and the receiving hypothalamic areas of the VIP-ir and AVP-ir fibers, which shared similar morphological features with those found in SCN, were similar to the patterns observed in diurnal and nocturnal animals. This finding supports the conservative nature of this feature among different species. Morphometric analysis of SCN intrinsic neurons indicated homogeneity in the size of VIP-ir neurons in the SCN ventral portion and heterogeneity in the size of two subpopulations of AVP-ir neurons in the SCN dorsal portion. The distribution of fibers and morphometric features of these neuronal populations are described and compared with those of other species in the present study.

Shortening the learning curve in endoscopic endonasal skull base surgery: a reproducible polymer tumor model for the trans-sphenoidal trans-tubercular approach to retro-infundibular tumors.

BACKGROUND: Endoscopic endonasal skull base surgery attracts an increasing number of young neurosurgeons. This recent technique requires specific technical skills for the approaches to non-pituitary tumors (expanded endoscopic endonasal surgery). Actual residents' busy schedules carry the risk of compromising their laboratory training by limiting significantly the dedicated time for dissections. OBJECTIVE: To enhance and shorten the learning curve in expanded endoscopic endonasal skull base surgery, we propose a reproducible model based on the implantation of a polymer via an intracranial route to provide a pathological retro-infundibular expansive lesion accessible to a virgin expanded endoscopic endonasal route, avoiding the ethically-debatable need to hundreds of pituitary cases in live patients before acquiring the desired skills. METHODS: A polymer-based tumor model was implanted in 6 embalmed human heads via a microsurgical right fronto-temporal approach through the carotido-oculomotor cistern to mimic a retro-infundibular tumor. The tumor's position was verified by CT-scan. An endoscopic endonasal trans-sphenoidal trans-tubercular trans-planum approach was then carried out on a virgin route under neuronavigation tracking. RESULTS: Dissection of the tumor model from displaced surrounding neurovascular structures reproduced live surgery's sensations and challenges. Post-implantation CT-scan allowed the pre-removal assessment of the tumor insertion, its relationships as well as naso-sphenoidal anatomy in preparation of the endoscopic approach. CONCLUSION: Training on easily reproducible retro-infundibular approaches in a context of pathological distorted anatomy provides a unique opportunity to avoid the need for repetitive live surgeries to acquire skills for this kind of rare tumors, and may shorten the learning curve for endoscopic endonasal surgery.

Immunohistochemical analysis of the colocalization of corticotropin-releasing hormone receptor and glucocorticoid receptor in kisspeptin neurons in the hypothalamus of female rats.

Kisspeptin, a neuropeptide encoded by Kiss1 gene, plays pivotal roles in the regulation of reproductive function. Recently various stressors and stress-induced molecules such as corticotropin-releasing hormone (CRH) and corticosterone have been shown to inhibit Kiss1 expression in rat hypothalamus. To determine whether CRH and glucocorticoids directly act on kisspeptin neurons, we examined the colocalization of CRH receptor (CRH-R) and glucocorticoid receptor (GR) in kisspeptin neurons in the female rat hypothalamus. Double-labeling immunohistochemistry revealed that most kisspeptin neurons in the anteroventral periventricular nucleus and periventricular nucleus continuum (AVPV/PeN), and arcuate nucleus (ARC) expressed CRH-R. We also observed a few close appositions of CRH immunoreactive fibers on some of kisspeptin neurons in AVPV/PeN and ARC. On the other hand, most kisspeptin neurons in AVPV/PeN expressed GR, whereas only a few of kisspeptin neurons in ARC expressed GR. Altogether, our study provides neuroanatomical evidence of the direct modulation of kisspeptin neurons by CRH and glucocorticoids and suggests that stress-induced CRH and glucocorticoids inhibit gonadotropin secretion via the kisspeptin system.