RESUMO
The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Using a combination of anatomical and in vivo two-photon imaging approaches, we unequivocally show that blood flows unidirectionally from the SCN to the OVLT, that blood flow rate displays daily oscillations with a higher rate at night than in the day, and that circulating vasopressin can access portal vessels. These findings highlight a previously unknown central nervous system communication pathway, which, like that of the pituitary portal system, could allow neurosecretions to reach nearby target sites in OVLT, avoiding dilution in the systemic blood. In both of these brain portal pathways, the target sites relay signals broadly to both the brain and the rest of the body.
Assuntos
Núcleo Supraquiasmático , Núcleo Supraquiasmático/fisiologia , Animais , Camundongos , Hipotálamo/metabolismo , Hipotálamo/irrigação sanguínea , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Encéfalo/metabolismo , Sistema Porta , Masculino , Vasopressinas/metabolismo , Vasopressinas/sangue , Circulação Cerebrovascular/fisiologia , Ritmo Circadiano/fisiologiaRESUMO
BACKGROUND: There is evidence of altered resting hypothalamic activity patterns and connectivity prior to a migraine, however it remains unknown if these changes are driven by changes in overall hypothalamic activity levels. If they are, it would corroborate the idea that changes in hypothalamic function result in alteration in brainstem pain processing sensitivity, which either triggers a migraine headache itself or allows an external trigger to initiate a migraine headache. We hypothesise that hypothalamic activity increases immediately prior to a migraine headache and this is accompanied by altered functional connectivity to pain processing sites in the brainstem. METHODS: In 34 migraineurs and 26 healthy controls, we collected a series comprising 108 pseudo-continuous arterial spin labelling images and 180 gradient-echo echo planar resting-state functional magnetic resonance volumes to measure resting regional cerebral blood flow and functional connectivity respectively. Images were pre-processed and analysed using custom SPM12 and Matlab software. RESULTS: Our results reflect that immediately prior to a migraine headache, resting regional cerebral blood flow decreases in the lateral hypothalamus. In addition, resting functional connectivity strength decreased between the lateral hypothalamus and important regions of the pain processing pathway, such as the midbrain periaqueductal gray, dorsal pons, rostral ventromedial medulla and cingulate cortex, only during this critical period before a migraine headache. CONCLUSION: These data suggest altered hypothalamic function and connectivity in the period immediately prior to a migraine headache and supports the hypothesis that the hypothalamus is involved in migraine initiation.
Assuntos
Circulação Cerebrovascular/fisiologia , Hipotálamo/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Vias Neurais/fisiopatologia , Adulto , Tronco Encefálico/fisiopatologia , Feminino , Humanos , Hipotálamo/irrigação sanguínea , Imageamento por Ressonância Magnética , MasculinoRESUMO
The arcuate nucleus (Arc) integrates circulating hormonal and metabolic signals to control energy expenditure and intake. One of the most important routes that enables the Arc to sense circulating molecules is through the median eminence (ME), which lacks a typical blood-brain barrier. However, the mechanism by which circulating molecules reach the Arc neurons remains unclear. This review focuses on what is known to date regarding the special structure and permeability of the ME vasculature and active transport of circulating molecules from the ME to the Arc. Recent studies have demonstrated that the ME displays angiogenic behavior that is expected to provide high vascular permeability. Parenchymal diffusion of circulating molecules from the ME vasculature is size-dependent, and tanycytes actively transport circulating molecules from the ME to the Arc. Finally, we highlight structural plasticity of the Arc and ME as playing an important role in maintaining energy balance homeostasis.
Assuntos
Núcleo Arqueado do Hipotálamo/irrigação sanguínea , Núcleo Arqueado do Hipotálamo/metabolismo , Barreira Hematoencefálica/metabolismo , Ingestão de Energia/fisiologia , Eminência Mediana/irrigação sanguínea , Eminência Mediana/metabolismo , Animais , Humanos , Hipotálamo/irrigação sanguínea , Hipotálamo/metabolismoRESUMO
TITLE: Linfoma B intravascular hipotalamico en una paciente inmunocompetente.
Assuntos
Hipotálamo/irrigação sanguínea , Linfoma de Células B/patologia , Neoplasias Vasculares/patologia , Idoso , Terapia Combinada , Confusão/etiologia , Irradiação Craniana , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Hipotireoidismo/etiologia , Imunocompetência , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/terapia , Invasividade Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Transtornos do Sono do Ritmo Circadiano/etiologia , Neoplasias Vasculares/complicações , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/terapia , Vasopressinas/deficiência , Redução de PesoRESUMO
BACKGROUND: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood-retinal barrier (BRB) and blood-brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. METHODS: BBB and BRB permeability were assessed using 14C-sucrose and 99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. RESULTS: High-fat feeding caused increased entry of 14C-sucrose and 99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to 14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to 99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of 99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for 14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. CONCLUSIONS: Blood-brain barrier and blood-retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in 14C-sucrose and 99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial carbonic anhydrase inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Inibidores da Anidrase Carbônica/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Topiramato/uso terapêutico , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica/efeitos adversos , Hipocampo/irrigação sanguínea , Hipocampo/metabolismo , Hipotálamo/irrigação sanguínea , Hipotálamo/metabolismo , Masculino , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Proteínas de Junções Íntimas/metabolismoRESUMO
Cluster headache is an excruciating, strictly one-sided pain syndrome with attacks that last between 15 minutes and 180 minutes and that are accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. The pain is so severe that female patients describe each attack as worse than childbirth. The past decade has seen remarkable progress in the understanding of the pathophysiological background of cluster headache and has implicated the brain, particularly the hypothalamus, as the generator of both the pain and the autonomic symptoms. Anatomical connections between the hypothalamus and the trigeminovascular system, as well as the parasympathetic nervous system, have also been implicated in cluster headache pathophysiology. The diagnosis of cluster headache involves excluding other primary headaches and secondary headaches and is based primarily on the patient's symptoms. Remarkable progress has been achieved in developing effective treatment options for single cluster attacks and in developing preventive measures, which include pharmacological therapies and neuromodulation.
Assuntos
Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/tratamento farmacológico , Cefaleia Histamínica/epidemiologia , Diagnóstico Diferencial , Humanos , Hipotálamo/irrigação sanguínea , Neuroimagem/métodos , Qualidade de Vida/psicologiaRESUMO
Intraluminal monofilament occlusion of the middle cerebral artery (MCAO) in mice is the most used rodent model to study the pathophysiology of stroke. However, this model often shows brain damage in regions not supplied by the MCA such as the hypothalamus, hippocampus and thalamus. Several studies have suggested some explanations on these localized infarcts. We aim to provide an alternative explanation which could allow each experimenter to better grasp the MCAO model. We propose that the MCA occlusion by the monofilament also occludes deep and small cerebral arteries arising directly from the internal carotid artery, proximally to the origin of MCA. Then, drawbacks and pitfalls of the MCAO model must be appreciated and the almost systematic risk of inducing lesions in some unwanted territories for neuroanatomical reasons, i.e. vascular connections between deep arteries and hypothalamic, thalamic and hippocampal areas in rodents has to be integrated.
Assuntos
Modelos Animais de Doenças , Hipocampo/patologia , Hipotálamo/patologia , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Tálamo/patologia , Animais , Artéria Carótida Interna/patologia , Artéria Carótida Interna/fisiopatologia , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Hipocampo/irrigação sanguínea , Hipotálamo/irrigação sanguínea , Infarto da Artéria Cerebral Média/etiologia , Tálamo/irrigação sanguíneaRESUMO
Gonadotropin-releasing hormone (GnRH) controls mammalian reproduction via the hypothalamic-pituitary-gonadal (hpg) axis, acting on gonadotrope cells in the pituitary gland that express the GnRH receptor (GnRHR). Cells expressing the GnRHR have also been identified in the brain. However, the mechanism by which GnRH acts on these potential target cells remains poorly understood due to the difficulty of visualizing and identifying living GnRHR neurons in the central nervous system. We have developed a mouse strain in which GnRHR neurons express a fluorescent marker, enabling the reliable identification of these cells independent of the hormonal status of the animal. In this study, we analyze the GnRHR neurons of the periventricular hypothalamic nucleus in acute brain slices prepared from adult female mice. Strikingly, we find that the action potential firing pattern of these neurons alternates in synchrony with the estrous cycle, with pronounced burst firing during the preovulatory period. We demonstrate that GnRH stimulation is sufficient to trigger the conversion from tonic to burst firing in GnRHR neurons. Furthermore, we show that this switch in the firing pattern is reversed by a potent GnRHR antagonist. These data suggest that endogenous GnRH acts on GnRHR neurons and triggers burst firing in these cells during late proestrus and estrus. Our data have important clinical implications in that they indicate a novel mode of action for GnRHR agonists and antagonists in neurons of the central nervous system that are not part of the classical hpg axis.
Assuntos
Potenciais de Ação/fisiologia , Ciclo Estral/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Capilares/ultraestrutura , Ciclo Estral/efeitos dos fármacos , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Antagonistas de Hormônios/farmacologia , Hipotálamo/irrigação sanguínea , Hipotálamo/efeitos dos fármacos , Hipotálamo/ultraestrutura , Imuno-Histoquímica , Camundongos Transgênicos , Microscopia Confocal , Microscopia Eletrônica , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Neurônios/ultraestrutura , Receptores LHRH/antagonistas & inibidores , Receptores LHRH/metabolismo , Técnicas de Cultura de TecidosRESUMO
OBJECTIVE: Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. RESEARCH DESIGN AND METHODS: In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. RESULTS: In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. CONCLUSIONS: Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior.
Assuntos
Cognição/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina/fisiologia , Sobrepeso/fisiopatologia , Administração Intranasal , Adulto , Índice de Massa Corporal , Encéfalo/fisiologia , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Cognição/efeitos dos fármacos , Fissura/fisiologia , Diabetes Mellitus Tipo 2/psicologia , Comportamento Alimentar/fisiologia , Feminino , Homeostase/efeitos dos fármacos , Humanos , Fome/fisiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Hipotálamo/irrigação sanguínea , Inibição Psicológica , Insulina/administração & dosagem , Insulina/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Obesidade/fisiopatologia , Obesidade/psicologia , Sobrepeso/psicologia , Córtex Pré-Frontal/irrigação sanguíneaRESUMO
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.
Assuntos
Diabetes Insípido/prevenção & controle , Hipotálamo/irrigação sanguínea , Microcirurgia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Cadáver , Artérias Cerebrais/anatomia & histologia , Artérias Cerebrais/cirurgia , Diabetes Insípido/etiologia , Humanos , Hipotálamo/anatomia & histologia , Hipotálamo/cirurgia , Complicações Pós-Operatórias/etiologiaRESUMO
Insulin signaling in the hypothalamus plays an important role in food intake and glucose homeostasis. Hypothalamic neuronal functions are modulated by glial cells; these form an extensive network connecting the neurons and cerebral vasculature, known as the neurovascular unit (NVU). Brain pericytes are periendothelial accessory structures of the blood-brain barrier and integral members of the NVU. However, the interaction between pericytes and neurons is largely unexplored. Here, we investigate whether brain pericytes could affect hypothalamic neuronal insulin signaling. Our immunohistochemical observations demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting immunoreactivity of platelet-derived growth factor receptor ß (a pericyte marker), and laminin, a basal lamina marker. We then exposed a murine hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor ß without changing its expression or localization in cytosolic or plasma membrane fractions. These results suggest that pericytes, rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by releasing soluble factors under physiological conditions in the NVU.
Assuntos
Meios de Cultivo Condicionados/metabolismo , Hipotálamo/citologia , Resistência à Insulina , Insulina/metabolismo , Pericitos/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Hipotálamo/irrigação sanguínea , Camundongos , Pericitos/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Receptor de Insulina/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de SinaisRESUMO
Hypothalamus communication with the rest of the brain and peripheral target tissues is critically important for many physiological and psychological functions. These functions include maintaining neuroendocrine circadian rhythms and managing affective processes. The hypothalamus maintains both direct neural connections within the brain and it also controls a variety of neuroendocrine processes that can influence target tissues throughout the body. Dysregulation of the hypothalamic pituitary adrenal axis and hyperactivity of the subgenual cortex are both frequently observed in depression. However, many details of how the hypothalamus, the hypothalamic pituitary adrenal (HPA) axis, and the subgenual cingulate interact with each other are unknown. We hypothesized that resting-state functional connectivity between the hypothalamus and the subgenual cortex would be associated with altered circadian rhythm in patients with depression and depressive symptoms. We also hypothesized that this would be most apparent in patients that have major depression with psychotic symptoms, who typically have the most robust HPA-axis dysregulation. Resting-state functional magnetic resonance imaging (fMRI) scans were collected to observe low-frequency resting-state functional connectivity patterns of the hypothalamus in 39 healthy participants, 39 patients with major depression, and 22 patients with major depression with psychotic symptoms. Hourly overnight measures of cortisol secretion and multiple measures of psychiatric symptom severity were also collected on all. Strong hypothalamic functional connectivity with the subgenual cortex was observed in healthy participants. This connectivity was significantly reduced in patients with psychotic major depression. Increased cortisol secretion during the circadian nadir and reduced connectivity were both associated with symptom severity. Reduced connectivity and high cortisol secretion during the circadian nadir are both useful for explaining a significant amount of variance in symptom severity that occurs between healthy participants and depressed patients. However, only cortisol secretion was useful for explaining the severity of symptoms within the depressed groups. This study suggests that the communication between the hypothalamus and the subgenual cortex is disrupted in patients with major depression with psychotic features. It also suggests that these disruptions are associated with increased symptom severity and may be a cause or a consequence of cortisol dysregulation.
Assuntos
Córtex Cerebral/fisiopatologia , Transtorno Depressivo Maior/patologia , Hipotálamo/fisiopatologia , Vias Neurais/fisiopatologia , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Mapeamento Encefálico , Córtex Cerebral/irrigação sanguínea , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Seguimentos , Humanos , Hidrocortisona/sangue , Hipotálamo/irrigação sanguínea , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/irrigação sanguínea , Oxigênio/sangue , Descanso , Adulto JovemRESUMO
Food intake is influenced by a complex regulatory system involving the integration of a wide variety of sensory inputs across multiple brain areas. Over the past decade, advances in neuroimaging using functional MRI (fMRI) have provided valuable insight into these pathways in the human brain. This review provides an outline of the methodology of fMRI, introducing the widely used blood oxygenation level-dependent contrast for fMRI and direct measures of cerebral blood flow using arterial spin labelling. A review of fMRI studies of the brain's response to taste, aroma and oral somatosensation, and how fat is sensed and mapped in the brain in relation to the pleasantness of food, and appetite control is given. The influence of phenotype on individual variability in cortical responses is addressed, and an overview of fMRI studies investigating hormonal influences (e.g. peptide YY, cholecystokinin and ghrelin) on appetite-related brain processes provided. Finally, recent developments in MR technology at ultra-high field (7 T) are introduced, highlighting the advances this can provide for fMRI studies to investigate the neural underpinnings in nutrition research. In conclusion, neuroimaging methods provide valuable insight into the mechanisms of flavour perception and appetite behaviour.
Assuntos
Regulação do Apetite , Encéfalo/fisiologia , Circulação Cerebrovascular , Neurônios/fisiologia , Resposta de Saciedade , Percepção Gustatória , Transferência de Tecnologia , Pesquisa Biomédica/tendências , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Congressos como Assunto , Neuroimagem Funcional , Humanos , Hipotálamo/irrigação sanguínea , Hipotálamo/fisiologia , Hipotálamo/fisiopatologia , Imageamento por Ressonância Magnética , Ciências da Nutrição/métodos , Ciências da Nutrição/tendências , Obesidade/fisiopatologiaRESUMO
Current knowledge about small-world networks underlying emotions is sparse, and confined to functional magnetic resonance imaging (fMRI) studies using resting-state paradigms. This fMRI study applied Eigenvector Centrality Mapping (ECM) and functional connectivity analysis to reveal neural small-world networks underlying joy and fear. Joy and fear were evoked using music, presented in 4-min blocks. Results show that the superficial amygdala (SF), laterobasal amygdala (LB), striatum, and hypothalamus function as computational hubs during joy. Out of these computational hubs, the amygdala nuclei showed the highest centrality values. The SF showed functional connectivity during joy with the mediodorsal thalamus (MD) and nucleus accumbens (Nac), suggesting that SF, MD, and Nac modulate approach behavior in response to positive social signals such as joyful music. The striatum was functionally connected during joy with the LB, as well as with premotor cortex, areas 1 and 7a, hippocampus, insula and cingulate cortex, showing that sensorimotor, attentional, and emotional processes converge in the striatum during music perception. The hypothalamus showed functional connectivity during joy with hippocampus and MD, suggesting that hypothalamic endocrine activity is modulated by hippocampal and thalamic activity during sustained periods of music-evoked emotion. Our study indicates high centrality of the amygdala nuclei groups within a functional network underlying joy, suggesting that these nuclei play a central role for the modulation of emotion-specific activity within this network.
Assuntos
Tonsila do Cerebelo/irrigação sanguínea , Corpo Estriado/irrigação sanguínea , Felicidade , Hipotálamo/irrigação sanguínea , Música/psicologia , Vias Neurais/irrigação sanguínea , Estimulação Acústica , Adulto , Mapeamento Encefálico , Emoções , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Oxigênio/sangue , Adulto JovemRESUMO
Animal studies suggest that insulin action in the brain is involved in the regulation of peripheral insulin sensitivity. Whether this holds true in humans is unknown. Using intranasal application of insulin to the human brain, we studied the impacts of brain insulin action on whole-body insulin sensitivity and the mechanisms involved in this process. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic glucose clamp before and after intranasal application of insulin and placebo in randomized order in lean and obese men. After insulin spray application in lean subjects, a higher glucose infusion rate was necessary to maintain euglycemia compared with placebo. Accordingly, clamp-derived insulin sensitivity index improved after insulin spray. In obese subjects, this insulin-sensitizing effect could not be detected. Change in the high-frequency band of heart rate variability, an estimate of parasympathetic output, correlated positively with change in whole-body insulin sensitivity after intranasal insulin. Improvement in whole-body insulin sensitivity correlated with the change in hypothalamic activity as assessed by functional magnetic resonance imaging. Intranasal insulin improves peripheral insulin sensitivity in lean but not in obese men. Furthermore, brain-derived peripheral insulin sensitization is associated with hypothalamic activity and parasympathetic outputs. Thus, the findings provide novel insights into the regulation of insulin sensitivity and the pathogenesis of insulin resistance in humans.
Assuntos
Glicemia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Hipotálamo/efeitos dos fármacos , Resistência à Insulina , Insulina/farmacologia , Obesidade , Sistema Nervoso Parassimpático/efeitos dos fármacos , Administração Intranasal , Adulto , Circulação Cerebrovascular/efeitos dos fármacos , Neuroimagem Funcional , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Hipotálamo/irrigação sanguínea , Infusões Intravenosas , Insulina/administração & dosagem , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
PAT4, the fourth member of the SLC36/proton dependent amino acid transporter (PAT) family, is a high-affinity, low capacity electroneutral transporter of neutral amino acids like proline and tryptophan. It has also been associated with the function of mTORC1, a complex in the mammalian target of rapamycin (mTOR) pathway. We performed in situ hybridization and immunohistological analysis to determine the expression profile of PAT4, as well as an RT-PCR study on tissue from mice exposed to leucine. We performed a phylogenetic analysis to determine the evolutionary origin of PAT4. The in situ hybridization and the immunohistochemistry on mouse brain sections and hypothalamic cells showed abundant PAT4 expression in the mouse brain intracellularly in both inhibitory and excitatory neurons, partially co-localizing with lysosomal markers and epithelial cells lining the ventricles. Its location in epithelial cells around the ventricles indicates a transport of substrates across the blood brain barrier. Phylogenetic analysis showed that PAT4 belongs to an evolutionary old family most likely predating animals, and PAT4 is the oldest member of that family.
Assuntos
Sistemas de Transporte de Aminoácidos/metabolismo , Encéfalo/metabolismo , Plexo Corióideo/metabolismo , Células Epiteliais/metabolismo , Neurônios/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Animais , Western Blotting , Encéfalo/irrigação sanguínea , Membrana Celular/metabolismo , Expressão Gênica , Hipocampo/irrigação sanguínea , Hipocampo/metabolismo , Hipotálamo/irrigação sanguínea , Hipotálamo/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Leucina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Filogenia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The blood-brain barrier (BBB) is a barrier that prevents free access of blood-derived substances to the brain through the tight junctions and maintains a specialized brain environment. Circumventricular organs (CVOs) lack the typical BBB. The fenestrated vasculature of the sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO) and area postrema (AP), allows parenchyma cells to sense a variety of blood-derived information, including osmotic ones. In the present study, we utilized immunohistochemistry to examine changes in the expression of NG2 and platelet-derived growth factor receptor beta (PDGFRB) in the OVLT, SFO and AP of adult mice during chronic osmotic stimulation. The expression of NG2 and PDGFRB was remarkably prominent in pericytes, although these angiogenesis-associated proteins are highly expressed at pericytes of developing immature vasculature. The chronic salt loading prominently increased the expression of NG2 in the OVLT and SFO and that of PDGFRB in the OVLT, SFO and AP. The vascular permeability of low-molecular-mass tracer fluorescein isothiocyanate was increased significantly by chronic salt loading in the OVLT and SFO but not AP. In conclusion, the present study demonstrates changes in pericyte expression of NG2 and PDGFRB and vascular permeability in the sensory CVOs by chronic osmotic stimulation, indicating active participation of the vascular system in osmotic homeostasis.
Assuntos
Antígenos/metabolismo , Área Postrema/metabolismo , Permeabilidade Capilar , Hipotálamo/metabolismo , Pericitos/metabolismo , Proteoglicanas/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Órgão Subfornical/metabolismo , Animais , Antígenos/genética , Área Postrema/irrigação sanguínea , Área Postrema/citologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Hipotálamo/irrigação sanguínea , Hipotálamo/citologia , Camundongos , Camundongos Endogâmicos C57BL , Osmorregulação , Pericitos/citologia , Proteoglicanas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Cloreto de Sódio/farmacologia , Órgão Subfornical/irrigação sanguínea , Órgão Subfornical/citologiaRESUMO
Schizophrenia is considered a neurodevelopmental disorder with a multifactorial pathogenesis where autoimmune factors may play a significant role. The aim of this study was to verify the presence of anti-brain autoantibodies in the serum of schizophrenic patients compared to healthy controls. Autoantibodies against brain were detected by the immunofluorescence method, utilizing sections of rat hippocampus and hypothalamus and of monkey cerebellum. Three different fluorescence patterns were observed, staining the nucleus-cytoplasm of neurons, the neuroendothelial of blood vessel and the neurofilaments. Search for other organ-specific and non organ-specific autoantibodies was performed in all sera by indirect immunofluorescence method, enzyme linked immunosorbent assay and chemiluminescence immunoassay. Results showed a significant association between schizophrenia and anti-brain autoantibodies against the neuroendothelium of blood vessel in hypothalamus, hippocampus and cerebellum; a significant nuclear and cytoplasmic staining of neurons was assessed only for the hippocampus. No other significant association was found, except between schizophrenia and anti-nuclear autoantibodies on HEp-2 cells. In conclusion, these results support the hypothesis of a significant association between schizophrenia and circulating anti-brain autoantibodies, suggesting a diffuse reactivity against the neuroendothelium of blood vessel and highlighting a nuclear and cytoplasmic staining of the neurons of hippocampus.
Assuntos
Anticorpos Antinucleares/metabolismo , Autoanticorpos/sangue , Encéfalo/imunologia , Esquizofrenia/sangue , Animais , Autoanticorpos/imunologia , Encéfalo/metabolismo , Estudos de Casos e Controles , Cerebelo/irrigação sanguínea , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Haplorrinos , Hipocampo/irrigação sanguínea , Humanos , Hipotálamo/irrigação sanguínea , Masculino , Neurônios , Ratos , Esquizofrenia/diagnóstico , Esquizofrenia/imunologiaRESUMO
In acute experiments in conscious rabbits was studied protective action of selective blocker of histamine H3-receptor betahistine (2mg/kg i/v) against histological changes in precentral and postcentral gyrus, as well as in temporal lobe of cerebral cortex, thalamus, hypothalamus, and cerebellum, arising in case of modeling of whole body wide-frequency vibration. Betahistine attenuates edematous and degenerative changes in neurons and reciprocal glial reaction, caused by vibration, but does not eliminate edema in perivascular spaces. This effect may be related to the improvement of blood supply as a result of of vasodilatory action and decrease of oxygen consumption via vestibuloprotective effect.
Assuntos
beta-Histina/farmacologia , Cerebelo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Edema/tratamento farmacológico , Agonistas dos Receptores Histamínicos/farmacologia , Hipotálamo/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Cerebelo/irrigação sanguínea , Cerebelo/patologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/patologia , Edema/etiologia , Edema/patologia , Feminino , Hipotálamo/irrigação sanguínea , Hipotálamo/patologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Coelhos , Vibração/efeitos adversosRESUMO
BACKGROUND/PURPOSE: Alternating hypothalamic-pituitary-adrenal axis mechanisms would lead to multiple organs dysfunction or failure. Herein, we attempt to assess whether hypothalamic inflammation and ischemic and oxidative damage that occurred during heatstroke (HS) can be affected by hyperbaric oxygen (HBO2) therapy in streptozotocin-induced diabetic rats. METHODS: In this study, anesthetized diabetic rats, immediately after the onset of HS, were divided into two major groups and given the normobaric air (21% O2 at 1.0 atmospheres absolute) or HBO2 (100% O2 at 2.0 atmospheres absolute). HS was induced by exposing the animals to heat stress (43°C). Another group of anesthetized diabetic rats was kept at normothermic state and used as controls. RESULTS: The survival time values for the HBO2-treated HS-diabetic rats increased form the control values of 78-82 minutes to new values of 184-208 minutes. HBO2 therapy caused a reduction of HS-induced cellular ischemia (e.g., increased cellular levels of glutamate and lactate/pyruvate ratio), hypoxia (e.g., decreased cellular levels of PO2), inflammation (e.g., increased cellular levels of interleukin-1ß, tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase), and oxidative damage (e.g., increased values of nitric oxide, 2,3-dihydroxybenzoic acid, glycerol, and neuronal damage score) in the hypothalamus of the diabetic rats. CONCLUSION: Our results suggest that, in diabetic animals, HBO2 therapy may improve outcomes of HS in part by reducing heat-induced activated inflammation and ischemic and oxidative damage in the hypothalamus and other brain regions.