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Sample records for hypothalamic anteroventral periventricular

  1. Periventricular Leukomalacia

    Science.gov (United States)

    ... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Periventricular leukomalacia (PVL) is characterized by the death of the white matter of the brain due to softening of the ...

  2. Functional hypothalamic amenorrhea due to increased CRH tone in melanocortin receptor 2-deficient mice.

    Science.gov (United States)

    Matsuwaki, Takashi; Nishihara, Masugi; Sato, Tsuyoshi; Yoda, Tetsuya; Iwakura, Yoichiro; Chida, Dai

    2010-11-01

    Exposure to chronic stressors results in dysregulation of the hypothalamic-pituitary-adrenal axis and a disruption in reproduction. CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis induces the secretion of ACTH from the pituitary, which stimulates adrenal steroidogenesis via the specific cell-surface melanocortin 2 receptor (MC2R). Previously, we demonstrated that MC2R(-/-) mice had undetectable levels of corticosterone despite high ACTH levels. Here, we evaluated the reproductive functions of female MC2R(-/-) mice and analyzed the mechanism of the disrupted cyclicity of these mice. The expression of CRH in the paraventricular nucleus was significantly increased in MC2R(-/-) mice under nonstressed conditions. Although MC2R(-/-) females were fertile, they showed a prolonged estrous cycle. After hormonal stimulation, MC2R(-/-) females produced nearly-normal numbers of eggs, but slightly less than MC2R(+/-) females, and showed near-normal ovarian histology. During diestrus, the number of GnRH-positive cells in the medial preoptic area was significantly reduced in MC2R(-/-) females. CRH type 1 receptor antagonist restored estrous cyclicity in MC2R(-/-) females. Kisspeptin-positive areas in the arcuate nucleus were comparable, whereas kisspeptin-positive areas in the anteroventral periventricular nucleus in MC2R(-/-) females were significantly reduced compared with MC2R(+/-) females, suggesting that arcuate nucleus kisspeptin is not involved, but anteroventral periventricular nucleus kisspeptin may be involved, in the maintenance of estrous cyclicity. Our findings show that high levels of hypothalamic CRH disturb estrous cyclicity in the female animals and that the MC2R(-/-) female is a unique animal model of functional hypothalamic amenorrhea.

  3. Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit.

    Science.gov (United States)

    Larsen, P J; Seier, V; Fink-Jensen, A; Holst, J J; Warberg, J; Vrang, N

    2003-03-01

    Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic neuroendocrine neurones. Adult male rats received a systemic injection of the neuronal tracer Fluorogold (FG) 2 days before fixation, and subsequent double- and triple-labelling immunoflourescence analysis demonstrated that neuroendocrine CART-containing neurones were present in the anteroventral periventricular, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro-opiomelanocortin in the ventrolateral part, but completely absent from neuroendocrine neurones of the dorsomedial part. To assess the possible role of CART as a hypothalamic-releasing factor, immunoreactive CART was measured in blood samples from the long portal vessels connecting the median eminence with the anterior pituitary gland. Adult male rats were anaesthetized and the infundibular stalk exposed via a transpharyngeal approach. The long portal vessels were transected and blood collected in 30-min periods (one prestimulatory and three poststimulatory periods). Compared to systemic venous plasma samples, baseline concentrations of immunoreactive CART were elevated in portal plasma. Exposure to sodium nitroprusside hypotension triggered a two-fold elevation of portal CART42

  4. Prophylactic ethamsylate for periventricular haemorrhage.

    OpenAIRE

    Cooke, R W; Morgan, M E

    1984-01-01

    Drug prophylaxis with ethamsylate for periventricular haemorrhage in very low birthweight infants significantly reduced the incidence of periventricular haemorrhage in survivors. A reduction in abnormalities at follow up and in insertion of ventriculoperitoneal shunts was also noted.

  5. Bilateral Periventricular Nodular Heterotopia

    OpenAIRE

    J Gordon Millichap

    1998-01-01

    Two unrelated boys, ages 8 and 5 years, with a syndrome of bilateral periventricular nodular heterotopia (BPNH), regional cortical dysplasia, mild mental retardation, and frontonasal malformation (FNM) are reported from the Instituto di Neuropsychiatria Infantile, University of Pisa, Italy, and the Institute of Human Genetics, University of Minnesota Medical School, Minneapolis, MN.

  6. Periventricular Nodular Heterotopia and Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-02-01

    Full Text Available The clinical, MRI, and EEG findings in 54 patients (35 female, 19 male; aged 1 to 64 years with periventricular nodular heterotopia (PNH were analyzed in relation to epileptic outcome and genesis of epileptic discharges, in a study at the Neurological Institute and Epilepsy Surgery Center, Niguarda General Hospital, Milan, Italy.

  7. Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

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    Xin-Yuan Cao

    2018-01-01

    Full Text Available Triclosan (TCS, a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH, follicle-stimulating hormone (FSH and progesterone, and gonadotrophin-releasing hormone (GnRH mRNA with the lack of LH surge and elevation of prolactin (PRL. TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV and arcuate nucleus (ARC. Moreover, the estrogen (E2-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3 and thyroxine (T4 in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH and thyroid releasing hormone (TRH. In TCS mice, the treatment with Levothyroxine (L-T4 corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.

  8. Epilepsy Outcome in Periventricular Nodular Heterotopia

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    J Gordon Millichap

    2004-07-01

    Full Text Available The clinical, electroencephalographic, and neuroimaging features and course of seizures in 16 patients with periventricular (subependymal nodular heterotopia (PNH were investigated at the University of Bologna, Italy.

  9. Different critical perinatal periods and hypothalamic sites of oestradiol action in the defeminisation of luteinising hormone surge and lordosis capacity in the rat.

    Science.gov (United States)

    Sakakibara, M; Deura, C; Minabe, S; Iwata, Y; Uenoyama, Y; Maeda, K-I; Tsukamura, H

    2013-03-01

    Female rats show a gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do not because of brain defeminisation during the developmental period by perinatal oestrogen converted from androgen. The present study aimed to identify the site(s) of oestrogen action and the critical period for defeminising the mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such as steroidal manipulations, brain local implantation of oestradiol (E(2) ) or administration of an NMDA antagonist, were examined for their ability to show an E(2) -induced LH surge at adulthood. Lordosis behaviour was examined to compare the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c. oestradiol-benzoate administration on either the day before birth (E21), the day of birth (D0) or day 5 (D5) postpartum completely abolished the E(2) -induced LH surge at adulthood in female rats, although the same treatment did not inhibit lordosis. Perinatal castration on E21 or D0 partially rescued the E2-induced LH surge in genetically male rats, whereas castration from E21 to D5 totally rescued lordosis. Neonatal E(2) implantation in the anterior hypothalamus including the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the E(2) -induced LH surge in female rats, whereas E(2) implantation in the mid and posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis was not affected by neonatal E(2) implantation in any hypothalamic regions. In male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH surge. Taken together, these results suggest that an anterior hypothalamic region such as the AVPV/POA region is a perinatal site of oestrogen action where the GnRH/LH regulating system is defeminised to abolish the oestrogen-induced surge. The mechanism for defeminisation of the GnRH/LH surge system might be different from

  10. Magnetic resonance imaging of cystic periventricular leukomalacia

    International Nuclear Information System (INIS)

    Kadoi, Nobuaki; Nomura, Junko; Nowatari, Masahiko; Ohta, Takeo; Kamohara, Takashi; Yashiro, Kimio

    1990-01-01

    A study was performed to assess the values of magnetic resonance (MR) imaging in evaluation and the follow up of patients with cystic periventricular leukomalacia. Ten patients selected for MR imaging were diagnosed as having periventricular cystic lesions based on US scans. The range of gestational ages was 27 to 32 weeks, and the range of birth weights was 927 to 2,046 g. Twenty MR examinations were carried out using a 0.5 T superconducting system (Resona; Yokogawa). On the first MR examinations, taken by 6 months of age, low signal intensity lesions within the periventricular white matter, moderate ventriculomegaly with irregularity of the ventricular wall and delayed myelination were observed. These were the MR findings observed in the subacute stage of PVL. On the second or the third MR examinations, taken after 12 months of age, increased signal intensity in periventricular white matter on T 2 weighted images decreased volume of periventricular white matter and centrum semiovale and the ventriculomagaly with irregularity of ventricular wall were observed. However, progressions of myelination were proved to be not delayed in comparison with age matched controls. These were thought to be the MR findings of late stage of PVL. As the US findings of PVL have good correlation with pathologic changes revealed at autopsy, MR imaging can depict myelination and detect PVL lesion beyond the neonatal period. These observations demonstrate the value of the MR imaging for the follow up of the patients with PVL beyond the time of fontanel closure. (author)

  11. Periventricular heterotopia in common microdeletion syndromes.

    NARCIS (Netherlands)

    Kogelenberg, M. van; Ghedia, S.; McGillivray, G.; Bruno, D.; Leventer, R.; Macdermot, K.; Nelson, J.; Nagarajan, L.; Veltman, J.A.; Brouwer, A.P.M. de; McKinlay Gardner, R.J.; Bokhoven, J.H.L.M. van; Kirk, E.P.; Robertson, S.P.

    2010-01-01

    Periventricular heterotopia (PH) is a brain malformation characterised by heterotopic nodules of neurons lining the walls of the cerebral ventricles. Mutations in FLNA account for 20-24% of instances but a majority have no identifiable genetic aetiology. Often the co-occurrence of PH with a

  12. Differential diagnosis of disseminated periventricular calcifications

    International Nuclear Information System (INIS)

    Rieger, P.; Piepgras, U.

    1986-01-01

    Juvenile disseminated periventricular calcifications may occur in tuberous sclerosis, toxoplasmosis, cytomegaly, and in tuberculous meningitis. Cysticercosis, by contrast, does not result in corresponding intracerebral foci until an older age. Differential diagnosis is no problem if clinical findings are typical (tuberous sclerosis) or if serological verification is positive. However, any unclear clinical diagnosis can often be secured by CT. (orig.) [de

  13. Differential diagnosis of disseminated periventricular calcifications

    Energy Technology Data Exchange (ETDEWEB)

    Rieger, P.; Piepgras, U.

    1986-08-01

    Juvenile disseminated periventricular calcifications may occur in tuberous sclerosis, toxoplasmosis, cytomegaly, and in tuberculous meningitis. Cysticercosis, by contrast, does not result in corresponding intracerebral foci until an older age. Differential diagnosis is no problem if clinical findings are typical (tuberous sclerosis) or if serological verification is positive. However, any unclear clinical diagnosis can often be secured by CT.

  14. Deletion of Suppressor of Cytokine Signaling 3 from Forebrain Neurons Delays Infertility and Onset of Hypothalamic Leptin Resistance in Response to a High Caloric Diet.

    Science.gov (United States)

    McEwen, Hayden J L; Inglis, Megan A; Quennell, Janette H; Grattan, David R; Anderson, Greg M

    2016-07-06

    The cellular processes that cause high caloric diet (HCD)-induced infertility are poorly understood but may involve upregulation of suppressor of cytokine signaling (SOCS-3) proteins that are associated with hypothalamic leptin resistance. Deletion of SOCS-3 from brain cells is known to protect mice from diet-induced obesity, but the effects on HCD-induced infertility are unknown. We used neuron-specific SOCS3 knock-out mice to elucidate this and the effects on regional hypothalamic leptin resistance. As expected, male and female neuron-specific SOCS3 knock-out mice were protected from HCD-induced obesity. While female wild-type mice became infertile after 4 months of HCD feeding, infertility onset in knock-out females was delayed by 4 weeks. Similarly, knock-out mice had delayed leptin resistance development in the medial preoptic area and anteroventral periventricular nucleus, regions important for generation of the surge of GnRH and LH that induces ovulation. We therefore tested whether the suppressive effects of HCD on the estradiol-induced GnRH/LH surge were overcome by neuron-specific SOCS3 knock-out. Although only 20% of control HCD-mice experienced a preovulatory-like LH surge, LH surges could be induced in almost all neuron-specific SOCS3 knock-out mice on this diet. In contrast to females, HCD-fed male mice did not exhibit any fertility decline compared with low caloric diet-fed males despite their resistance to the satiety effects of leptin. These data show that deletion of SOCS3 delays the onset of leptin resistance and infertility in HCD-fed female mice, but given continued HCD feeding this state does eventually occur, presumably in response to other mechanisms inhibiting leptin signal transduction. Obesity is commonly associated with infertility in humans and other animals. Treatments for human infertility show a decreased success rate with increasing body mass index. A hallmark of obesity is an increase in circulating leptin levels; despite this, the

  15. Neuropeptide Y2 receptors in anteroventral BNST control remote fear memory depending on extinction training.

    Science.gov (United States)

    Verma, Dilip; Tasan, Ramon; Sperk, Guenther; Pape, Hans-Christian

    2018-03-01

    The anterior bed nucleus of stria terminalis (BNST) is involved in reinstatement of extinguished fear, and neuropeptide Y2 receptors influence local synaptic signaling. Therefore, we hypothesized that Y2 receptors in anteroventral BNST (BNSTav) interfere with remote fear memory and that previous fear extinction is an important variable. C57BL/6NCrl mice were fear-conditioned, and a Y2 receptor-specific agonist (NPY 3-36 ) or antagonist (JNJ-5207787) was applied in BNSTav before fear retrieval at the following day. Remote fear memory was tested on day 16 in two groups of mice, which had (experiment 1) or had not (experiment 2) undergone extinction training after conditioning. In the group with extinction training, tests of remote fear memory revealed partial retrieval of extinction, which was prevented after blockade of Y2 receptors in BNSTav. No such effect was observed in the group with no extinction training, but stimulation of Y2 receptors in BNSTav mimicked the influence of extinction during tests of remote fear memory. Pharmacological manipulation of Y2 receptors in BNSTav before fear acquisition (experiment 3) had no effect on fear memory retrieval, extinction or remote fear memory. Furthermore, partial retrieval of extinction during tests of remote fear memory was associated with changes in number of c-Fos expressing neurons in BNSTav, which was prevented or mimicked upon Y2 blockade or stimulation in BNSTav. These results indicate that Y2 receptor manipulation in BNSTav interferes with fear memory and extinction retrieval at remote stages, likely through controlling neuronal activity in BNSTav during extinction training. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Pseudotemporal Epilepsy with Periventricular Nodular Heterotopia

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    Aysun Ünal

    2006-04-01

    Full Text Available Scientific background: Periventricular nodular heterotopia (PNH that is one of the subgroups of neuronal migration disorders is associated with intractable epilepsy. However the etiopathogenesis of seizures in PNH patients are still unclear. Heterotopias are not involved in the epileptic network, alone. A complex relation between nodules, hippocampus and neocortex has been reported as the cause. Case: A 20 year-old male patient with intractable seizures is presented with ictal and interictal EEG findings compatible with right temporal lobe seizure. Although his first MRI was reported as hyperintensity in right hippocampus, repeated MRI examination according to epilepsy protocol revealed bilateral PNH, with no signal change in hippocampus. Conclusion: The aim of this case report is to discuss the importance of PNH in the differential diagnosis of intractable seizures, and to mention that neurologists and radiologists can easily miss these lesions, if the walls of ventricles are not checked carefully

  17. Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit

    DEFF Research Database (Denmark)

    Larsen, P J; Seier, V; Fink-Jensen, A

    2003-01-01

    Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalami......, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART......-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro...

  18. Hypothalamic demyelination causing panhypopituitarism.

    Science.gov (United States)

    Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

    2018-05-01

    Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

  19. Periventricular hypodensity in communicating hydrocephalus studied by metrizamide CT cisternography

    International Nuclear Information System (INIS)

    Hiratsuka, Hideo; Okada, Kodai; Takasato, Yoshio; Inaba, Yutaka; Tsuyumu, Matsutaira.

    1979-01-01

    Modification of periventricular hypodensity in suspected communicating hydrocephalus was investigated by metrizamide CT cisternography. Six to eight ml of metrizamide isotonic solution with a concentration of 170 mgI/ml was given through lumbar puncture and scanning was conducted 1, 3, 6, 24 and 48 hrs after injection. In addition to visual analysis of images, mean value and standard deviation were calculated for Hounsfield units of the regions of interest at the anterolateral angle of frontal horn and the time courses of the attenuation values were statistically compared to each other at each scanning time. The results were classified into four groups: 1) periventricular low density zone with gradual penetration of metrizamide therein; 2) periventricular low density zone without penetration of metrizamide therein; 3) minimal periventricular low density zone with minimal metrizamide penetration; and 4) no periventricular low density zone and no penetration of metrizamide. The presence of a periventricular low density zone with increase of the density after ventricular reflux of metrizamide would be an important criterion for CSF shunting operation in normal pressure hydrocephalus or communicating hydrocephalus. (author)

  20. Periventricular hyperintensity in children with hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Akbari, S.H.A.; Ragan, Dustin K. [St. Louis Children' s Hospital, Washington University School of Medicine, Department of Neurological Surgery, St. Louis, MO (United States); Limbrick, David D. [St. Louis Children' s Hospital, Washington University School of Medicine, Department of Neurological Surgery, St. Louis, MO (United States); McKinstry, Robert C.; Shimony, Joshua S. [St. Louis Children' s Hospital, Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Altaye, Mekibib [Cincinnati Children' s Hospital, Division of Biostatistics and Epidemiology, Cincinnati, OH (United States); Yuan, Weihong; Holland, Scott K. [Cincinnati Children' s Hospital, Department of Pediatric Radiology, Cincinnati, OH (United States); Mangano, Francesco T. [Cincinnati Children' s Hospital, Department of Pediatric Neurological Surgery, Cincinnati, OH (United States)

    2015-08-15

    Magnetic resonance images of children with hydrocephalus often include a rim of hyperintensity in the periventricular white matter (halo). The purpose of this study was to decide between the hypothesis that the halo is caused by cerebrospinal fluid (CSF) flow during the cardiac cycle, and the alternate hypothesis that the halo is caused by anatomical changes (stretching and compression of white matter). Participants were selected from a multicenter imaging study of pediatric hydrocephalus. We compared 19 children with hydrocephalus to a group of 52 controls. We quantified ventricle enlargement using the frontal-occipital horn ratio. We conducted qualitative and quantitative analysis of diffusion tensor imaging in the corpus callosum and posterior limb of the internal capsule. Parameters included the fractional anisotropy (FA), mean diffusivity, axial diffusivity and radial diffusivity. The halo was seen in 16 of the 19 children with hydrocephalus but not in the controls. The corpus callosum of the hydrocephalus group demonstrated FA values that were significantly decreased from those in the control group (P = 4 . 10{sup -6}), and highly significant increases were seen in the mean diffusivity and radial diffusivity in the hydrocephalus group. In the posterior limb of the internal capsule the FA values of the hydrocephalus group were higher than those for the control group (P = 0.002), and higher values in the hydrocephalus group were also noted in the axial diffusivity. We noted correlations between the diffusion parameters and the frontal-occipital horn ratio. Our results strongly support the hypothesis that the halo finding in hydrocephalus is caused by structural changes rather than pulsatile CSF flow. (orig.)

  1. Periventricular hyperintensity in children with hydrocephalus

    International Nuclear Information System (INIS)

    Akbari, S.H.A.; Ragan, Dustin K.; Limbrick, David D.; McKinstry, Robert C.; Shimony, Joshua S.; Altaye, Mekibib; Yuan, Weihong; Holland, Scott K.; Mangano, Francesco T.

    2015-01-01

    Magnetic resonance images of children with hydrocephalus often include a rim of hyperintensity in the periventricular white matter (halo). The purpose of this study was to decide between the hypothesis that the halo is caused by cerebrospinal fluid (CSF) flow during the cardiac cycle, and the alternate hypothesis that the halo is caused by anatomical changes (stretching and compression of white matter). Participants were selected from a multicenter imaging study of pediatric hydrocephalus. We compared 19 children with hydrocephalus to a group of 52 controls. We quantified ventricle enlargement using the frontal-occipital horn ratio. We conducted qualitative and quantitative analysis of diffusion tensor imaging in the corpus callosum and posterior limb of the internal capsule. Parameters included the fractional anisotropy (FA), mean diffusivity, axial diffusivity and radial diffusivity. The halo was seen in 16 of the 19 children with hydrocephalus but not in the controls. The corpus callosum of the hydrocephalus group demonstrated FA values that were significantly decreased from those in the control group (P = 4 . 10 -6 ), and highly significant increases were seen in the mean diffusivity and radial diffusivity in the hydrocephalus group. In the posterior limb of the internal capsule the FA values of the hydrocephalus group were higher than those for the control group (P = 0.002), and higher values in the hydrocephalus group were also noted in the axial diffusivity. We noted correlations between the diffusion parameters and the frontal-occipital horn ratio. Our results strongly support the hypothesis that the halo finding in hydrocephalus is caused by structural changes rather than pulsatile CSF flow. (orig.)

  2. A Case with Bilateral Periventricular Nodular Heterotopia Diagnosed as Depression

    Directory of Open Access Journals (Sweden)

    Melek Kandemir

    2010-06-01

    Full Text Available Periventricular nodular heterotopia is a form of neuronal migration abnormality. Periventricular nodular heterotopia can easily be recognized by cranial magnetic resonance imaging. The most common clinical appearance is epileptic seizures. In some cases, symptoms are accompanied with psychiatric complaints. In this article, we report a 33-year-old female with complaints of left-sided paresthesia induced by emotional stress. She had been followed at an outpatient psychiatry clinic for about 10 years with the diagnosis of somatization disorder. Her electroencephalography recordings -awake as well as during sleep- were found to be normal. The cranial magnetic resonance imaging showed bilateral periventricular nodular heterotopia. Her seizures were controlled with carbamazepine treatment. Partial epileptic seizures might also be observed, even though the cerebral heterotopic lesions are bilateral. When a history is obtained from a patient with somatoform complaints, it should be kept in mind that these symptoms might be seizures, and the patient should be questioned accordingly

  3. A Case with Bilateral Periventricular Nodular Heterotopia Diagnosed as Depression

    Directory of Open Access Journals (Sweden)

    Melek Kandemir

    2010-06-01

    Full Text Available Periventricular nodular heterotopia is a form of neuronal migration abnormality. Periventricular nodular heterotopia can easily be recognized by cranial magnetic resonance imaging. The most common clinical appearance is epileptic seizures. In some cases, symptoms are accompanied with psychiatric complaints. In this article, we report a 33-year-old female with complaints of left-sided paresthesia induced by emotional stress. She had been followed at an outpatient psychiatry clinic for about 10 years with the diagnosis of somatization disorder. Her electroencephalography recordings -awake as well as during sleep- were found to be normal. The cranial magnetic resonance imaging showed bilateral periventricular nodular heterotopia. Her seizures were controlled with carbamazepine treatment. Partial epileptic seizures might also be observed, even though the cerebral heterotopic lesions are bilateral. When a history is obtained from a patient with somatoform complaints, it should be kept in mind that these symptoms might be seizures, and the patient should be questioned accordingly.

  4. Familial bilateral periventricular nodular heterotopia mimics tuberous sclerosis.

    Science.gov (United States)

    Jardine, P E; Clarke, M A; Super, M

    1996-01-01

    A mother and daughter with an initial diagnosis of tuberous sclerosis are described. The daughter presented with partial seizures at the age of 8 months. Computed tomography showed uncalcified periventricular nodules which on magnetic resonance imaging were ovoid, almost contiguous, of grey matter density, and did not enhance with gadolinium. Brain imaging of her asymptomatic mother was similar. Absence of severe mental retardation, extracranial hamartomas, and depigmented patches distinguishes familial bilateral periventricular nodular heterotopia (FNH) from tuberous sclerosis. FNH is probably inherited as an X linked dominant with lethality in males. Images Figure 1 Figure 2 PMID:8787433

  5. Periventricular-intraventricular haemorrhage in low-birth-weight ...

    African Journals Online (AJOL)

    The prevalence of periventricular-intraventricular haemorrhage (PV-IVH) aInong very-low-birthweight infants at Baragwanath Hospital has not been well docwnented. In this prospective study, a total of 282 live-born infants with birth weights of 1 000 - 1 749 g were studied over a 41/2-month period. Every infant had at least ...

  6. computed tomography features of basal ganglia and periventricular

    African Journals Online (AJOL)

    HIV is probably the most common cause of basal ganglia and periventricular calcification today. on-enhanced computed tomography (NECT) shows diffuse cerebral atrophy in 90% of cases. Bilateral, symmetrical basal ganglia calcification is seen in 30% of cases, but virtually never before 1 year of age.1. CMV (FIG.2).

  7. Bilateral periventricular nodular heterotopia – neonatal cranial ultrasound.

    Directory of Open Access Journals (Sweden)

    A R Horn

    2010-03-01

    Full Text Available A female neonate was delivered at 30 weeks’ gestation to a mother with suspected bilateral periventricular nodular heterotopia (PNH on computed tomography brain scan. Antenatal ultrasound (US performed at 28 weeks’ gestation showed mild lateral cerebral ventricle dilatation, but no other fetal anomalies. Clinical examination revealed mild dysmorphic features: facial and skull asymmetry, square-shaped ears, and long tapering fingers. Chromosomal analysis showed a 46XX karyotype.

  8. Periventricular Nodular Heterotopia, Surgical Goal in Drug-Resistant Epilepsy

    Directory of Open Access Journals (Sweden)

    Fernando Velandia-Hurtado

    2014-09-01

    Full Text Available Introduction: Neuronal heterotopia is a migration disorder in which these cells do not complete their movement toward the cerebral cortex. Periventricular nodular heterotopia is the most frequently reported form, characterized by neuronal conglomerates adjacent to the lateral ventricles walls. About 90 % of patients with this condition suffer epilepsy at some point in their lives and the major proportion of them will be resistant to pharmacologic treatment. This makes an appropriate diagnostic approach necessary in order to determine which patients would benefit from surgical resection of the lesion, which in most cases offers a high rate of crisis control. Development: This article presents a review of the most important topics approached from the practice of periventricular nodular heterotopia pathophysiology, clinical features, diagnosis and therapy. It is aimed at exploring the role of this condition as a cause of intractable epilepsy. Conclusion: Pharmacologic treatment for resistant epilepsy will have a severe impact on patient’s quality of life. Periventricular nodular heterotopia is frequently associated to this condition, which must be successfully approached by the medical team attempting to an opportune diagnosis and defining which patients would benefit from surgical management. This positively impacts the quality of life of these patients and their caregivers.

  9. Hypothalamic Projections to the Optic Tectum in Larval Zebrafish

    Science.gov (United States)

    Heap, Lucy A.; Vanwalleghem, Gilles C.; Thompson, Andrew W.; Favre-Bulle, Itia; Rubinsztein-Dunlop, Halina; Scott, Ethan K.

    2018-01-01

    The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH) to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC)/stratum griseum periventriculare (SPV), and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil. PMID:29403362

  10. Hypothalamic Projections to the Optic Tectum in Larval Zebrafish

    Directory of Open Access Journals (Sweden)

    Lucy A. Heap

    2018-01-01

    Full Text Available The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC/stratum griseum periventriculare (SPV, and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil.

  11. MRI examination of West syndrome complicated by periventricular leukomalacia (PVL)

    International Nuclear Information System (INIS)

    Fukuda, Kuniaki; Yamashita, Akiko; Endo, Shoichi; Gouda, Tomoko

    2001-01-01

    The magnetic resonance imaging (MRI) findings of 19 low-birth-weight infants with periventricular leukomalacia (PVL) and cerebral palsy, 6 with West syndrome as a complication (group III) and 13 without it (group II), were compared with those of normal 13 low-birth-weight infants without PVL or cerebral palsy (group I) to investigate the pathogenetic mechanism of West syndrome. All of the subjects were born between 1989 and 1997, and there were no significant differences between the three groups in birth weight or age at the time of the examination. Although the gestation period was significantly longer in the group III (infants with West syndrome) than in group I (control infants), there was no significant difference was seen between group I and group II (infants with PVL and cerebral palsy). PVL was diagnosed by MRI, and the diagnostic standards included periventricular high signal intensity on T2-weighted images, decreased cerebral white matter, and deformity or enlargement of the lateral ventricles. The area of periventricular high signal intensity was significantly larger in group II and group III than in group I, and the occipital lobe white matter was significantly thinner in the former than the latter. The lateral ventricles were significantly larger in group II than in the other two groups. The area of the corpus callosum and the thickness of the splenium and trunk of the corpus callosum were significantly smaller in group II and group III than in group I, but the corpus callosum was significantly shorter in group III than in the other two groups. Findings in the brain stem showed a significantly smaller pons and medulla oblongata in group III than in group I, but there were no significant differences between group II and group I. The results of this study indicate that lower brainstem lesions as well as cerebral lesions are associated with the development of West syndrome. (K.H.)

  12. MRI examination of West syndrome complicated by periventricular leukomalacia (PVL)

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Kuniaki; Yamashita, Akiko; Endo, Shoichi [National Kagawa Children' s Hospital, Zentuji (Japan); Gouda, Tomoko

    2001-10-01

    The magnetic resonance imaging (MRI) findings of 19 low-birth-weight infants with periventricular leukomalacia (PVL) and cerebral palsy, 6 with West syndrome as a complication (group III) and 13 without it (group II), were compared with those of normal 13 low-birth-weight infants without PVL or cerebral palsy (group I) to investigate the pathogenetic mechanism of West syndrome. All of the subjects were born between 1989 and 1997, and there were no significant differences between the three groups in birth weight or age at the time of the examination. Although the gestation period was significantly longer in the group III (infants with West syndrome) than in group I (control infants), there was no significant difference was seen between group I and group II (infants with PVL and cerebral palsy). PVL was diagnosed by MRI, and the diagnostic standards included periventricular high signal intensity on T2-weighted images, decreased cerebral white matter, and deformity or enlargement of the lateral ventricles. The area of periventricular high signal intensity was significantly larger in group II and group III than in group I, and the occipital lobe white matter was significantly thinner in the former than the latter. The lateral ventricles were significantly larger in group II than in the other two groups. The area of the corpus callosum and the thickness of the splenium and trunk of the corpus callosum were significantly smaller in group II and group III than in group I, but the corpus callosum was significantly shorter in group III than in the other two groups. Findings in the brain stem showed a significantly smaller pons and medulla oblongata in group III than in group I, but there were no significant differences between group II and group I. The results of this study indicate that lower brainstem lesions as well as cerebral lesions are associated with the development of West syndrome. (K.H.)

  13. Hypothalamic glioma masquerading as craniopharyngioma

    Directory of Open Access Journals (Sweden)

    Sameer Vyas

    2013-01-01

    Full Text Available Hypothalamic glioma account for 10-15% of supratentorial tumors in children. They usually present earlier (first 5 years of age than craniopharyngioma. Hypothalamic glioma poses a diagnostic dilemma with craniopharyngioma and other hypothalamic region tumors, when they present with atypical clinical or imaging patterns. Neuroimaging modalities especially MRI plays a very important role in scrutinizing the lesions in the hypothalamic region. We report a case of a hypothalamic glioma masquerading as a craniopharyngioma on imaging along with brief review of both the tumors.

  14. MRI findings with periventricular leukomalacia. Correlation with neurological development

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Hisakazu; Yoshioka, Hiroshi; Hasegawa, Koh; Doi, Yasuo; Matsuo, Yasutaka; Murata, Miyuki; Sawada, Tadashi [Kyoto Prefectural Univ. of Medicine (Japan); Kotani, Hiromi; Goma, Hideyo

    1998-08-01

    In 22 infants with PVL, who were born at 35 weeks gestational age or less, correlation between severity of white matter lesions on MRI and developmental quotient (DQ) of infants was studied. MRI was obtained later than 7 months of age and the severity of white matter lesions was classified as follows: Group I: periventricular white matter is focally affected (n=7), Group II: periventricular white matter is diffusely affected (n=10), and Group III: subcortical white matter is also affected (n=5). Perinatal characteristics including gestational weeks, birth weight, Apgar score, procedure of delivery, and duration of mechanical ventilation revealed no significant differences between the groups. Seventeen infants developed cerebral palsy, while the other 5 infants (4 in Group I, 1 in Group II) showed normal development at 1 year of age, MRI of 4 among these 5 infants only revealed unilateral cysts around the anterior horn of lateral ventricles. Enjoji developmental test showed significant differences in gross motor DQ between Group I and III at both 1 and 2 corrected ages. Although more quantitative criteria will be required for precise classification, it is suggested that the severity of the white matter lesions on MRI is well correlated with gross motor development in PVL. (author)

  15. A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion.

    Science.gov (United States)

    Scott, Niv; Prigge, Matthias; Yizhar, Ofer; Kimchi, Tali

    2015-09-24

    It is commonly assumed, but has rarely been demonstrated, that sex differences in behaviour arise from sexual dimorphism in the underlying neural circuits. Parental care is a complex stereotypic behaviour towards offspring that is shared by numerous species. Mice display profound sex differences in offspring-directed behaviours. At their first encounter, virgin females behave maternally towards alien pups while males will usually ignore the pups or attack them. Here we show that tyrosine hydroxylase (TH)-expressing neurons in the anteroventral periventricular nucleus (AVPV) of the mouse hypothalamus are more numerous in mothers than in virgin females and males, and govern parental behaviours in a sex-specific manner. In females, ablating the AVPV TH(+) neurons impairs maternal behaviour whereas optogenetic stimulation or increased TH expression in these cells enhance maternal care. In males, however, this same neuronal cluster has no effect on parental care but rather suppresses inter-male aggression. Furthermore, optogenetic activation or increased TH expression in the AVPV TH(+) neurons of female mice increases circulating oxytocin, whereas their ablation reduces oxytocin levels. Finally, we show that AVPV TH(+) neurons relay a monosynaptic input to oxytocin-expressing neurons in the paraventricular nucleus. Our findings uncover a previously unknown role for this neuronal population in the control of maternal care and oxytocin secretion, and provide evidence for a causal relationship between sexual dimorphism in the adult brain and sex differences in parental behaviour.

  16. Functional Topography of Early Periventricular Brain Lesions in Relation to Cytoarchitectonic Probabilistic Maps

    Science.gov (United States)

    Staudt, Martin; Ticini, Luca F.; Grodd, Wolfgang; Krageloh-Mann, Ingeborg; Karnath, Hans-Otto

    2008-01-01

    Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we asked whether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matter damage. Eight patients with pre- and perinatally acquired left-sided…

  17. Like father, like son: periventricular nodular heterotopia and nonverbal learning disorder.

    Science.gov (United States)

    McCann, Marcia V; Pongonis, Stephen J; Golomb, Meredith R; Edwards-Brown, Mary; Christensen, Celanie K; Sokol, Deborah K

    2008-08-01

    Periventricular nodular heterotopia is a common malformation of cortical development in which the migration of developing neurons destined for the cerebral cortex is abbreviated. Bilateral periventricular nodular heterotopia is most commonly an X-linked disorder that involves mutations in the filamin A (FLNA) gene, but an autosomal recessive form and sporadic forms have been identified. To our knowledge, autosomal dominant transmission of isolated periventricular nodular heterotopia has not been reported. Periventricular nodular heterotopia has a heterogeneous phenotype, associated commonly with seizure disorder, and more recently with reading deficits and visual-spatial deficits in some patients. We present a father and son with bilateral periventricular nodular heterotopia and similar visual-spatial learning deficits, consistent with nonverbal learning disability.

  18. Computed tomography in hypothalamic hamartoma

    International Nuclear Information System (INIS)

    Mori, Koreaki; Takeuchi, Juji; Hanakita, Junya; Handa, Hajime; Nakano, Yoshihisa.

    1981-01-01

    Two cases of hypothalamic hamartoma were reported. Hypothalamic hamartoma is a rate tumor. The onset of symptoms is in infancy and early childhood. Clinical symptoms are composed of convulsive seizures, laughing spells and precocious puberty. CT finding of hypothalamic hamartoma is a mass in the suprasellar and interpeduncular cisterns which has the same density as the surrounding normal brain. The mass is not enhanced by injection of the contrast material and is easily differentiated from other masses in the suprasellar region. (author)

  19. MR appearance of hypothalamic hamartoma

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.J.; Leibrock, L.G.; Huseman, C.A.; Makos, M.M.

    1988-02-01

    Hypothalamic hamartoma is the most common detectable cerebral lesion causing precocious puberty. Two histologically confirmed cases were studied by computerized tomography (CT) and magnetic resonance (MR) imaging. T2 weighted, sagittal MR images were superior to CT in delineating the tumor from surrounding grey matter. The lesion was isointense to grey matter on T1 weighted images allowing exclusion of other hypothalamic tumors. MR will undoubtedly become the imaging modality of choice in the detection of hypothalamic hamartoma.

  20. Endoport-Assisted Microsurgical Treatment of a Ruptured Periventricular Aneurysm

    Directory of Open Access Journals (Sweden)

    Ching-Jen Chen

    2016-01-01

    Full Text Available Background and Importance. Ruptured periventricular aneurysms in patients with moyamoya disease represent challenging pathologies. The most common methods of treatment include endovascular embolization and microsurgical clipping. However, rare cases arise in which the location and anatomy of the aneurysm make these treatment modalities particularly challenging. Clinical Presentation. We report a case of a 34-year-old female with moyamoya disease who presented with intraventricular hemorrhage. CT angiography and digital subtraction angiography revealed an aneurysm located in the wall of the atrium of the right lateral ventricle. Distal endovascular access was not possible, and embolization risked the sacrifice of arteries supplying critical brain parenchyma. Using the BrainPath endoport system, the aneurysm was able to be accessed. Since the fusiform architecture of the aneurysm prevented clip placement, the aneurysm was ligated with electrocautery. Conclusion. We demonstrate the feasibility of endoport-assisted approach for minimally invasive access and treatment of uncommon, distally located aneurysms.

  1. Neonatal periventricular leukomalacia: real-time sonographic diagnosis with CT correlation

    International Nuclear Information System (INIS)

    Chow, P.P.; Horgan, J.G.; Taylor, K.J.W.

    1985-01-01

    The utility of real-time sonography in the diagnosis of neonatal periventricular leukomalacia (PVL) has been described only recently. Six cases are reported of PVL diagnosed by serial real-time scanning. The sonographic findings were correlated with the computed tomographic findings and the clinical history. In five of six infants in whom scanning was performed, characteristic multiseptated periventricular cavitations developed 2-3 weeks after birth or later. A transition from normal to increased periventricular echogenicity was often observed before the development of the periventricular cavitations in nonhemorrhagic PVL. The parenchymal abnormality demonstrated by sonography correlated well with an abnormal neurologic outcome. It is suggested that serial real-time scanning be performed in neonates whose history suggests the possibility of hypoxic-ischemic brain injury. Nonspecific predictors of PVL include seizures, apnea, disturbed mental status, abnormal muscle tone, and leg weakness

  2. ''Intraventricular'' hemorrhage and cystic periventricular leukomalacia in preterm infants: how are they related?

    NARCIS (Netherlands)

    Kusters, C.D.J.; Chen, M.L.; Follett, P.L.; Dammann, O.

    2009-01-01

    Intraventricular hemorrhage and cystic periventricular leukomalacia are often co-occurring characteristics of brain damage in preterm infants. Using data from 1016 infants born before 30 completed weeks' gestational age, we sought to clarify the relationship between severe intraventricular

  3. Hypothalamic neurogenesis persists in the aging brain and is controlled by energy-sensing IGF-I pathway.

    Science.gov (United States)

    Chaker, Zayna; George, Caroline; Petrovska, Marija; Caron, Jean-Baptiste; Lacube, Philippe; Caillé, Isabelle; Holzenberger, Martin

    2016-05-01

    Hypothalamic tanycytes are specialized glial cells lining the third ventricle. They are recently identified as adult stem and/or progenitor cells, able to self-renew and give rise to new neurons postnatally. However, the long-term neurogenic potential of tanycytes and the pathways regulating lifelong cell replacement in the adult hypothalamus are largely unexplored. Using inducible nestin-CreER(T2) for conditional mutagenesis, we performed lineage tracing of adult hypothalamic stem and/or progenitor cells (HySC) and demonstrated that new neurons continue to be born throughout adult life. This neurogenesis was targeted to numerous hypothalamic nuclei and produced different types of neurons in the dorsal periventricular regions. Some adult-born neurons integrated the median eminence and arcuate nucleus during aging and produced growth hormone releasing hormone. We showed that adult hypothalamic neurogenesis was tightly controlled by insulin-like growth factors (IGF). Knockout of IGF-1 receptor from hypothalamic stem and/or progenitor cells increased neuronal production and enhanced α-tanycyte self-renewal, preserving this stem cell-like population from age-related attrition. Our data indicate that adult hypothalamus retains the capacity of cell renewal, and thus, a substantial degree of structural plasticity throughout lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Visual navigation in adolescents with early periventricular lesions: knowing where, but not getting there.

    Science.gov (United States)

    Pavlova, Marina; Sokolov, Alexander; Krägeloh-Mann, Ingeborg

    2007-02-01

    Visual navigation in familiar and unfamiliar surroundings is an essential ingredient of adaptive daily life behavior. Recent brain imaging work helps to recognize that establishing connectivity between brain regions is of importance for successful navigation. Here, we ask whether the ability to navigate is impaired in adolescents who were born premature and suffer congenital bilateral periventricular brain damage that might affect the pathways interconnecting subcortical structures with cortex. Performance on a set of visual labyrinth tasks was significantly worse in patients with periventricular leukomalacia (PVL) as compared with premature-born controls without lesions and term-born adolescents. The ability for visual navigation inversely relates to the severity of motor disability, leg-dominated bilateral spastic cerebral palsy. This agrees with the view that navigation ability substantially improves with practice and might be compromised in individuals with restrictions in active spatial exploration. Visual navigation is negatively linked to the volumetric extent of lesions over the right parietal and frontal periventricular regions. Whereas impairments of visual processing of point-light biological motion are associated in patients with PVL with bilateral parietal periventricular lesions, navigation ability is specifically linked to the frontal lesions in the right hemisphere. We suggest that more anterior periventricular lesions impair the interrelations between the right hippocampus and cortical areas leading to disintegration of neural networks engaged in visual navigation. For the first time, we show that the severity of right frontal periventricular damage and leg-dominated motor disorders can serve as independent predictors of the visual navigation disability.

  5. Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

    Science.gov (United States)

    Matsumoto, Naoyuki; Hoshiba, Yoshio; Morita, Kazuya; Uda, Natsu; Hirota, Miwako; Minamikawa, Maki; Ebisu, Haruka; Shinmyo, Yohei; Kawasaki, Hiroshi

    2017-03-15

    Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Medical therapy of hypothalamic diseases

    International Nuclear Information System (INIS)

    Werder, K. von; Mueller, O.A.

    1985-01-01

    Hormonal disturbances caused by hypothalamic pathology can be treated effectively by target hormone replacement in the case of failure of glandotropic hormone secretion. Hyposomatotropism in children has to be substituted by parenteral administration of growth hormone. In addition gonadotropins respectively gonadotropin releasing factor have to be given in order to restore fertility in hypothalamic hypogonadism. Posterior pituitary failure can be adequately replaced by administration of analogues of antidiuretic hormone. Hypothalamic pathology causing hypersecretion of anterior pituitary hormones may also be accessable to medical treatment. This pertains particularly to hyperprolactinemia and precocious puberty. However, there is no medical therapy so far for hypothalamic disturbances leading to veterative dysfunction like disturbances of temperature regulation and control of thirst and polyphagia. In this situation symptomatic correction of the abnormality represents the only possibility to keep these patients alive. (Author)

  7. Hypothalamic lipophagy and energetic balance

    OpenAIRE

    Singh, Rajat

    2011-01-01

    Autophagy is a conserved cellular turnover process that degrades unwanted cytoplasmic material within lysosomes. Through ?in bulk? degradation of cytoplasmic proteins and organelles, including lipid droplets, autophagy helps provide an alternative fuel source, in particular, when nutrients are scarce. Recent work demonstrates a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in regulation of food intake and energy balance. The induction of autophagy in hypothalamic ne...

  8. [Functional hypothalamic amenorrhea].

    Science.gov (United States)

    Stárka, Luboslav; Dušková, Michaela

    2015-10-01

    Functional hypothalamic amenorrhea (FHA) besides pregnancy and syndrome of polycystic ovary is one of the most common causes of secondary amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). FHA is a form of the defence of organism in situations where life functions are more important than reproductive function. FHA is reversible; it can be normalized after ceasing the stress situation. There are three types of FHA: weight loss related, stress-related, and exercise-related amenorrhea. The final consequences are complex hormonal changes manifested by profound hypoestrogenism. Additionally, these patients present mild hypercortisolemia, low serum insulin levels, low insulin-like growth factor 1 (IGF-1) and low total triiodothyronine. Women health in this disorder is disturbed in several aspects including the skeletal system, cardiovascular system, and mental problems. Patients manifest a decrease in bone mass density, which is related to an increase in fracture risk. Therefore, osteopenia and osteoporosis are the main long-term complications of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in the lipid profile. FHA patients present significantly higher depression and anxiety and also sexual problems compared to healthy subjects.

  9. Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus.

    Science.gov (United States)

    Cassone, V M; Speh, J C; Card, J P; Moore, R Y

    1988-01-01

    A detailed analysis of the cytoarchitecture, retinohypothalamic tract (RHT) projections, and immunohistochemical localization of major cell and fiber types within the hypothalamic suprachiasmatic nuclei (SCN) was conducted in five mammalian species: two species of opossum, the domestic cat, the guinea pig, and the house mouse. Cytoarchitectural and immunohistochemical studies were conducted in three additional species of marsupial mammals and in the domestic pig. The SCN in this diverse transect of mammalian taxonomy bear striking similarities. First, the SCN are similar in location, lying close to the third ventricle (3V) dorsal to the optic chiasm (OC), with a cytoarchitecture characterized by small, tightly packed neurons. Second, in all groups studied, the SCN receive bilateral retinal input. Third, the SCN contain immunohistochemically similar elements. These similarities suggest that the SCN developed characteristic features early in mammalian phylogeny. Some details of SCN organization vary among the species studied. In marsupials, vasopressin-like immunoreactive (VP-LI) and vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cells codistribute primarily in the dorsomedial aspects of the SCN, while in eutherians, VP-LI and VIP-LI cells are separated into SCN subnuclei. Furthermore, the marsupial RHT projects to the periventricular dorsomedial region, whereas the eutherian RHT projects more ventrally in the SCN into the zone that typically contains VIP-LI perikarya.

  10. 47 patients with FLNA associated periventricular nodular heterotopia.

    Science.gov (United States)

    Lange, Max; Kasper, Burkhard; Bohring, Axel; Rutsch, Frank; Kluger, Gerhard; Hoffjan, Sabine; Spranger, Stephanie; Behnecke, Anne; Ferbert, Andreas; Hahn, Andreas; Oehl-Jaschkowitz, Barbara; Graul-Neumann, Luitgard; Diepold, Katharina; Schreyer, Isolde; Bernhard, Matthias K; Mueller, Franziska; Siebers-Renelt, Ulrike; Beleza-Meireles, Ana; Uyanik, Goekhan; Janssens, Sandra; Boltshauser, Eugen; Winkler, Juergen; Schuierer, Gerhard; Hehr, Ute

    2015-10-15

    Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20

  11. The significance of periventricular lucency on computed tomography: experimental study with canine hydrocephalus

    International Nuclear Information System (INIS)

    Murata, T.; Handa, H.; Mori, K.; Nakano, Y.

    1981-01-01

    In order to investigate the pathogenesis of periventricular lucency (PVL) in hydrocephalus, CT scans were performed with monitoring of the epidural pressure in a series of dogs with hydrocephalus induced with kaolin. PVL of various degrees was detected in the experimental animals, which disappeared immediately after a shunting operation. Correlations have been attempted between PVL on CT scans and histological examinations, contrast enhancement studies, metrizamide ventriculography, and measurement of regional cerebral blood flow in the periventricular white matter. PVL in hydrocephalus is considered to represent acute edema or chronic CSF retention in the periventricular white matter caused by an increase of water content. In other words, it is regarded as a sign of existing or preceding intraventricular hypertension on CT scan, and seems to be a reversible phenomenon to some extent. PVL may therefore become an indication for a shunt. (orig.)

  12. Cerebral gigantism of hypothalamic origin.

    Science.gov (United States)

    Ranke, M B; Bierich, J R

    1983-04-01

    In five cases of Sotos Syndrome serum somatomedin activities were measured. In two of these cases elevated levels and an increased secretion of growth hormone was observed. In one case (index case) a suspected hypothalamic tumor mass could be excluded, but hydrocephalus with increased intracranial pressure was present. The pathogenesis of gigantism in this syndrome is discussed.

  13. A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia

    NARCIS (Netherlands)

    Kogelenberg, M. van; Lerone, M.; Toni, T. De; Divizia, M.T.; Brouwer, A.P. de; Veltman, J.A.; Bokhoven, J.H.L.M. van; Robertson, S.P.

    2011-01-01

    We report on a follow-up evaluation of a male with a phenotype including craniosynostosis, periventricular nodular heterotopia, and neurodevelopmental delay. He was initially assigned a clinical diagnosis of Fontaine-Farriaux syndrome (FFS) as an infant although now, with improved delineation of

  14. MRI Findings of Coexistence of Ectopic Neurohypophysis, Corpus Callosum Dysgenesis, and Periventricular Neuronal Heterotopia

    Directory of Open Access Journals (Sweden)

    Harun Arslan

    2014-01-01

    Full Text Available Ectopic neurohypophysis is a pituitary gland abnormality, which can accompany growth hormone deficiency associated with dwarfism. Here we present magnetic resonance imaging (MRI findings of a rare case of ectopic neurohypophysis, corpus callosum dysgenesis, and periventricular neuronal heterotopia coexisting, with a review of the literature.

  15. Somatostatin in the rat periventricular nucleus: sex differences and effect of gonadal steroids

    NARCIS (Netherlands)

    Vugt, van H.H.; Heijning, van de B.J.M.; Beek, van der E.M.

    2008-01-01

    In the rat, the sexual dimorphism in growth hormone release is driven by sex steroids, and is suggested to result mainly from differences in somatostatin (SOM) release patterns from the median eminence. We studied the effect of gonadal steroids on SOM peptide-containing cells in the periventricular

  16. Correlation between MRI and clinical profiles of periventricular leukomalacia in children

    International Nuclear Information System (INIS)

    Fan Xiaoying; Xiao Jiangxi; Jiang Xuexiang; Tang Guangjian

    2003-01-01

    Objective: To study the relationship between MRI and clinical profiles of periventricular leukomalacia (PVL) in children. Methods: The clinical and MRI findings in 34 cases with PVL were retrospectively analyzed. Results: (1) Periventricular hyperintensity on T 2 WI was more prominent in the preterm-group than that in the term-group, and P value was 0.000; (2) Cortical lesion and subcortical leukomalacia was seen in 9 of 19 cases in the children with PVL born at term, but detected in only 1/15 in the preterm-group. P value was 0.020; (3) Seizure was common in term children. P value was 0.036; (4) The degree of reduction of periventricular white matter correlated with motor impairment and mental retardation in all children, and P values were 0.002 and 0.000, respectively. The thinning of the corpus callosum also correlated with mental retardation and P value was 0.012. The degree of reduction of periventricular white matter correlated with visual impairment in preterm-group. Conclusion: The end-stage PVL can been clearly displayed by MRI, and gestational age and clinical manifestation were closely related to the findings of MRI

  17. De Morsier syndrome associated with periventricular nodular heterotopia: case reporte Síndrome de De Morsier associada a heterotopia nodular periventricular: relato de caso

    Directory of Open Access Journals (Sweden)

    Mônica Jaques Spinosa

    2007-09-01

    Full Text Available INTRODUCTION: Septo-optic dysplasia (De Morsier syndrome is defined as the association between optic nerve hypoplasia, midline central nervous system malformations and pituitary dysfunction. CASE REPORT: Third child born to nonconsanguineous parents, female, adequate pre-natal medical care, cesarean term delivery due to breech presentation, Apgar score 3 at the first minute and 8 at 5 minutes, symptomatic hypoglycemia at 18 hours. Neurological follow-up identified a delay in acquisition of motor and language developmental milestones. Epileptic generalized seizures began at 12 months and were controlled with phenobarbital. EEG was normal. MRI revealed agenesis of the pituitary stalk, hypoplasia of the optic chiasm and periventricular nodular heterotopia. Ophthalmologic evaluation showed bilateral optic disk hypoplasia. Endocrine function laboratory tests revealed primary hypothyroidism and hyperprolactinemia. CONCLUSION: The relevance of this case report relies on its uniqueness, since periventricular heterotopia had not been described in association with septo-optic dysplasia until 2006.INTRODUÇÃO: Displasia septo-óptica (síndrome de De Morsier é definida como a associação entre hipoplasia do nervo óptico, malformações de linha média do sistema nervoso central e disfunção pituitária. RELATO DE CASO: Terceiro filho, pais não consangüíneos, sexo feminino, pré-natal adequado, parto cesário a termo por apresentação pélvica, Apgar 3 no primeiro minuto e 8 no quinto minuto, hipoglicemia sintomática com 18 horas de vida. Durante o acompanhamento neurológico identificou-se atraso na aquisição dos marcos de desenvolvimento motor e linguagem. Crises epilépticas generalizadas iniciaram com 12 meses de vida sendo controladas com fenobarbital. EEG era normal. Ressonância magnética revelou agenesia de haste pituitária, hipoplasia de quiasma óptico e heterotopia nodular periventricular. Avaliação oftalmológica demonstrou

  18. Bariatric Surgery in Hypothalamic Obesity

    OpenAIRE

    Bingham, Nathan C.; Rose, Susan R.; Inge, Thomas H.

    2012-01-01

    Craniopharyngiomas (CP) are epithelial neoplasms generally found in the area of the pituitary and hypothalamus. Despite benign histology, these tumors and/or their treatment often result in significant, debilitating disorders of endocrine, neurological, behavioral, and metabolic systems. Severe obesity is observed in a high percentage of patients with CP resulting in significant comorbidities and negatively impacting quality of life. Obesity occurs as a result of hypothalamic damage and disru...

  19. Unilateral periventricular heterotopia and epilepsy in a girl with Ehlers–Danlos syndrome

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    Salvatore Savasta

    2015-01-01

    Conclusion: To our knowledge, this is the first report of unilateral periventricular heterotopia associated with Ehlers–Danlos syndrome. We first hypothesized a mosaicism as the cause of both, a unilateral localization of the heterotopias and a favorable long-term course with good response to anticonvulsant therapy; however, intriguingly, we could not demonstrate a mosaicism as the genetic condition in our patient and the neuroradiological findings and the favorable clinical outcome still remain unexplained.

  20. Early echographic findings in non-hemorrhagic periventricular leukomalacia of the premature infant

    International Nuclear Information System (INIS)

    Delaporte, B.; Dehan, M.; Labrune, M.; Imbert, M.C.

    1985-01-01

    The ultrasonic detection of periventricular leukomalacia is described in two neonatal patients. Confirmation of this condition by CT and post mortem was obtained in one case. CT scan and further echography was positive in the other. Neither patient had evidence of an intracranial hemorrhage. It is suggested that echography is of value in the early diagnosis of this lesion which may be similar to intraparenchymal hemorrhage in its mechanism and prognosis. (orig.)

  1. Fulminant citrobacter meningitis with multiple periventricular abscesses in a three-month-old infant

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    P. Anoop

    Full Text Available Citrobacter, a Gram-negative enteric bacillus, is a rare cause of septicemia and meningitis, seldom reported beyond the neonatal period. It is characterized by a fulminant clinical course and a high incidence of complications, including brain abscesses. We studied a three-month-old infant with Citrobacter meningitis, who developed acute communicating hydrocephalus and multiple periventricular brain abscesses while on treatment. The patient died, despite intensive antibiotic treatment directed towards the causative organism, C. diversus.

  2. Periventricular nodular heterotopia and bilateral intraventricular xanthogranulomas in 22q11.2 deletion syndrome

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    Moogeh Baharnoori

    2017-09-01

    Full Text Available 22q11.2 deletion syndrome (22q11DS is the most common pathogenic copy number variant in humans. Neuropsychiatric phenotypes, including schizophrenia, are prominent. Imaging studies of individuals with this syndrome show a variety of abnormalities that may indicate abnormal neuronal migration. Here we present the neuroimaging and neuropathologic features of a 22q11DS patient with bilateral periventricular nodular heterotopias (PNH and intraventricular xanthogranulomas that were identified by post-mortem examination.

  3. Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia

    Science.gov (United States)

    Ferland, Russell J.; Batiz, Luis Federico; Neal, Jason; Lian, Gewei; Bundock, Elizabeth; Lu, Jie; Hsiao, Yi-Chun; Diamond, Rachel; Mei, Davide; Banham, Alison H.; Brown, Philip J.; Vanderburg, Charles R.; Joseph, Jeffrey; Hecht, Jonathan L.; Folkerth, Rebecca; Guerrini, Renzo; Walsh, Christopher A.; Rodriguez, Esteban M.; Sheen, Volney L.

    2009-01-01

    Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in ‘Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315–1325, 1998; Sheen et al. in ‘Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69–76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in ‘MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789–801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (α-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventicular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell

  4. Severe Cystic Periventricular Leukomalacia in a Premature Infant with Capnocytophaga Sepsis

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    W. Thomas Bass

    2014-11-01

    Full Text Available Capnocytophaga is an opportunistic gram-negative anaerobic bacillus found in the oropharyngeal cavity of mammals and is associated with periodontal disease in humans. Sepsis, osteomyelitis, lung abscess, endocarditis, and meningitis have been reported in humans following animal bites. Perinatal infection with Capnocytophaga is infrequent and is generally considered to have a low risk of morbidity to the mother and fetus. We report a case of neonatal Capnocytophaga sepsis associated with the development of severe cystic periventricular leukomalacia

  5. Proton magnetic resonance spectroscopy of periventricular white matter and hippocampus in obstructive sleep apnea patients

    International Nuclear Information System (INIS)

    Kızılgöz, Volkan; Aydın, Hasan; Tatar, İdil Güneş; Hekimoğlu, Baki; Ardıç, Sadık; Fırat, Hikmet; Dönmez, Cem

    2013-01-01

    The purpose of this study was to diagnose the hypoxic impairment by Magnetic resonance spectroscopy (MRS), an advanced MR imaging technique, which could not be visualised by routine imaging methods in patients with obstructive sleep apnea (OSA). 20 OSA patients and 5 controls were included in this prospective research. MRS was performed on these 25 subjects to examine cerebral hypoxemia in specific regions (periventricular white matter and both hippocampi). Polysomnography was assumed as the gold standard. Statistical analysis was assessed by Mann-Whitney U test and Receiver operating characteristics (ROC) curve for NAA/Cho, NAA/Cr and Cho/Cr ratios. In the periventricular white matter, NAA/Cho ratio in OSA patients was significantly lower than in the control group (p<0.05). There were no statistical differences between the OSA and the control group for NAA/Cho, NAA/Cr and Cho/Cr ratios for both hippocampal regions. Additionally, Cho/Cr ratio in the periventricular white matter region of OSA group was higher than in the control group (p<0.05). Hypoxic impairment induced by repeated episodes of apnea leads to significant neuronal damage in OSA patients. MRS provides valuable information in the assessment of hypoxic ischemic impairment by revealing important metabolite ratios for the specific areas of the brain

  6. Bariatric surgery in hypothalamic obesity

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    Nathan eBingham

    2012-02-01

    Full Text Available Craniopharyngiomas (CP are epithelial neoplasms generally found in the area of the pituitary and hypothalamus. Despite benign histology, these tumors and/or their treatment often result in significant, debilitating disorders of endocrine, neurological, behavioral, and metabolic systems. Severe obesity is observed in a high percentage of patients with CP resulting in significant comorbidities and negatively impacting quality of life. Obesity occurs as a result of hypothalamic damage and disruption of normal homeostatic mechanisms regulating energy balance. Such pathological weight gain, termed hypothalamic obesity (HyOb, is often severe and refractory to therapy.Unfortunately, neither lifestyle intervention nor pharmacotherapy has proven truly effective in the treatment of CP-HyOb. Given the limited choices and poor results of these treatments, several groups have examined bariatric surgery as a treatment alternative for patients with CP-HyOb. While a large body of evidence exists supporting the use of bariatric surgery in the treatment of exogenous obesity and its comorbidities, its role in the treatment of HyOb has yet to be well defined. To date, the existing literature on bariatric surgery in CP-HyOb is largely limited to case reports and series with short term follow-up. Here we review the current reports on the use of bariatric surgery in the treatment of CP-HyOb. We also compare these results to those reported for other populations of HyOb, including Prader-Willi Syndrome and patients with melanocortin signaling defects. While initial reports of bariatric surgery in CP-HyOb are promising, their limited scope makes it difficult to draw any substantial conclusions as to the long term safety and efficacy of bariatric surgery in CP-HyOb. There continues to be a need for more robust, controlled, prospective trials with long term follow-up in order to better define the role of bariatric surgery in the treatment of all types of hypothalamic

  7. Computed tomography demonstration of a hypothalamic metastasis

    International Nuclear Information System (INIS)

    Chakeres, D.W.

    1983-01-01

    This case report describes a patient who presented with panhypopituitarism secondary to hypothalamic metastasis. A primary hypothalamic abnormality was suggested by computed tomographic (CT) demonstration of a small enhancing circular mass centered within the hypothalamus. Sellar radiographs and cerebral angiography were normal. (orig.)

  8. Computed tomography demonstration of a hypothalamic metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Chakeres, D.W.

    1983-05-01

    This case report describes a patient who presented with panhypopituitarism secondary to hypothalamic metastasis. A primary hypothalamic abnormality was suggested by computed tomographic (CT) demonstration of a small enhancing circular mass centered within the hypothalamus. Sellar radiographs and cerebral angiography were normal.

  9. Dietary sugars, not lipids, drive hypothalamic inflammation

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    Yuanqing Gao

    2017-08-01

    Conclusions: Combined overconsumption of fat and sugar, but not the overconsumption of fat per se, leads to excessive CML production in hypothalamic neurons, which, in turn, stimulates hypothalamic inflammatory responses such as microgliosis and eventually leads to neuronal dysfunction in the control of energy metabolism.

  10. Dynamic Susceptibility Contrast Perfusion Magnetic Resonance Imaging Demonstrates Reduced Periventricular Cerebral Blood Flow in Dogs with Ventriculomegaly

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    Martin J. Schmidt

    2017-08-01

    Full Text Available The nature of ventriculomegaly in dogs is still a matter of debate. Signs of increased intraventricular pressure and atrophy of the cerebral white matter have been found in dogs with ventriculomegaly, which would imply increased intraventricular pressure and, therefore, a pathological condition, i.e., to some extent. Reduced periventricular blood flow was found in people with high elevated intraventricular pressure. The aim of this study was to compare periventricular brain perfusion in dogs with and without ventriculomegaly using perfusion weighted-magnetic-resonance-imaging to clarify as to whether ventriculomegaly might be associated with an increase in intraventricular pressure. Perfusion was measured in 32 Cavalier King Charles spaniels (CKCS with ventriculomegaly, 10 CKCSs were examined as a control group. Cerebral blood flow (CBF was measured using free-hand regions of interest (ROI in five brain regions: periventricular white matter, caudate nucleus, parietal cortex, hippocampus, and thalamus. CBF was significantly lower in the periventricular white matter of the dogs with ventriculomegaly (p = 0.0029 but not in the other ROIs. Reduction of periventricular CBF might imply increase of intraventricular pressure in ventriculomegaly.

  11. Hypothalamic pathogenesis of type 2 diabetes.

    Science.gov (United States)

    Koshiyama, Hiroyuki; Hamamoto, Yoshiyuki; Honjo, Sachiko; Wada, Yoshiharu; Lkeda, Hiroki

    2006-01-01

    There have recently been increasing experimental and clinical evidences suggesting that hypothalamic dysregulation may be one of the underlying mechanisms of abnormal glucose metabolism. First, increased hypothalamic-pituitary-adrenal axis activity induced by uncontrollable excess stress may cause diabetes mellitus as well as dyslipidemia, visceral obesity, and osteoporosis with some resemblance to Cushing's disease. Second, several molecules are known to be expressed both in pancreas and hypothalamus; adenosine triphosphate-sensitive potassium channels, malonyl-CoA, glucokinase, and AMP-activated protein kinase. Those molecules appear to form an integrated hypothalamic system, which may sense hypothalamic fuel status, especially glucose level, and inhibit action of insulin on hepatic gluconeogenesis, thereby forming a brain-liver circuit. Third, hypothalamic resistance to insulin as an adiposity signal may be involved in pathogenesis of peripheral insulin resistance. The results with mice with a neuron-specific disruption of the insulin receptor gene or those lacking insulin receptor substrate 2 in hypothalamus supported this possibility. Finally, it has very recently been suggested that dysregulation of clock genes in hypothalamus may cause abnormal glucose metabolism. Taken together, it is plausible that some hypothalamic abnormality may underlie at least some portion of type 2 diabetes or insulin resistance in humans, and this viewpoint of hypothalamic pathogenesis of type 2 diabetes may lead to the development of new drugs for type 2 diabetes.

  12. Mutation in filamin A causes periventricular heterotopia, developmental regression, and West syndrome in males.

    Science.gov (United States)

    Masruha, Marcelo R; Caboclo, Luis O S F; Carrete, Henrique; Cendes, Iscia L; Rodrigues, Murilo G; Garzon, Eliana; Yacubian, Elza M T; Sakamoto, Américo C; Sheen, Volney; Harney, Megan; Neal, Jason; Hill, R Sean; Bodell, Adria; Walsh, Christopher; Vilanova, Luiz C P

    2006-01-01

    Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray-matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X-linked dominant pattern. Heterozygotic female patients usually remain asymptomatic until the second or third decade of life, when they may have predominantly focal seizures, whereas hemizygotic male fetuses typically die in utero. Recent studies have also reported mutations in FLNA in male patients with PH who are cognitively normal. We describe PH in three male siblings with PH due to FLNA, severe developmental regression, and West syndrome. The study includes the three affected brothers and their parents. Video-EEG recordings and magnetic resonance image (MRI) scanning were performed on all individuals. Mutations for FLNA were detected by using polymerase chain reaction (PCR) on genomic DNA followed by single-stranded conformational polymorphism (SSCP) analysis or sequencing. Two of the siblings are monozygotic twins, and all had West syndrome with hypsarrhythmia on EEG. MRI of the brain revealed periventricular nodules of cerebral gray-matter intensity, typical for PH. Mutational analyses demonstrated a cytosine-to-thymidine missense mutation (c. C1286T), resulting in a threonine-to-methionine amino acid substitution in exon 9 of the FLNA gene. The association between PH and West syndrome, to our knowledge, has not been previously reported. Males with PH have been known to harbor FLNA mutations, although uniformly, they either show early lethality or survive and have a normal intellect. The current studies show that FLNA mutations can cause periventricular heterotopia, developmental regression, and West syndrome in male patients, suggesting that this type of FLNA mutation may contribute to severe neurologic deficits.

  13. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder

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    Karen Blackmon

    2016-01-01

    Full Text Available Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC. Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE open-access database, were analyzed to compare groups on (1 blinded review of high-resolution T1-weighted research sequences; and (2 quantitative measurement of white matter hypointensity (WMH volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC, also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly.

  14. Prenatal diagnosis of periventricular nodular heterotopia in borderline ventriculomegaly using sonography and magnetic resonance imaging.

    Science.gov (United States)

    Sahinoglu, Zeki; Yapicier, Ozlem; Ozcan, Nahit

    2016-10-01

    Periventricular nodular heterotopia (PNH) is usually missed on prenatal sonographic examinations, even on targeted scans. Irregular ventricular walls on axial view and irregular square-shaped lateral ventricles on coronal view are suggestive of PNH in the early third trimester. To achieve an early prenatal diagnosis, it is important to keep in mind the possible coexistence of PNH with brain malformations such as ventriculomegaly, posterior fossa anomalies, or agenesis of corpus callosum. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:510-513, 2016. © 2016 Wiley Periodicals, Inc.

  15. Problems of the decrease in periventricular density due to hypoxia in computer tomograms of new-born infants

    Energy Technology Data Exchange (ETDEWEB)

    Kotlarek, F.; Bruell, D.; Sturm, K.W.; Zeumer, H.

    200 premature and mature neonates with clinical evidence of hypoxia or traumatic encephalopathy were examined by cranial computerized tomography (CT) during the first two weeks postnatally. The findings were compared with those in a control-group consisting of 14 neonates with extraneural malformations. Cerebral hemorrhages were easily identified by their high density, in CT images. Bilateral areas of lowered density within the periventricular white matter, however, could not always be attributed to irreversible tissue damage prior to about 14 days after the hypoxic event in term newborns, and in preterm infants even later. During this early period of life an apparent decrease of periventricular density was regularily observed that must not be mistaken for a pathological change. In two cases persistent periventricular areas of decreased density were caused by neuropathologically verified foci of incomplete leucomalacia.

  16. The problems of the decrease in periventricular density due to hypoxia in computer tomograms of new-born infants

    International Nuclear Information System (INIS)

    Kotlarek, F.; Bruell, D.; Sturm, K.W.; Zeumer, H.

    1982-01-01

    200 premature and mature neonates with clinical evidence of hypoxia or traumatic encephalopathy were examined by cranial computerized tomography (CT) during the first two weeks postnatally. The findings were compared with those in a ''control-group'' consisting of 14 neonates with extraneural malformations. Cerebral hemorrhages were easily identified by their high density, in CT images. Bilateral areas of lowered density within the periventricular white matter, however, could not always be attributed to irreversible tissue damage prior to about 14 days after the hypoxic event in term newborns, and in preterm infants even later. During this early period of life an apparent decrease of periventricular density was regularily observed that must not be mistaken for a pathological change. In two cases persistent periventricular areas of decreased density were caused by neuropathologically verified foci of incomplete leucomalacia. (orig.) [de

  17. Periventricular leukomalacia

    Science.gov (United States)

    ... nih.gov/pubmed/15635108 . Volpe JJ. Hypoxic-ischemic encephalopathy: neuropathology and pathogenesis. In: Volpe JJ, ed. Neurology of the Newborn . 5th ed. Philadelphia, PA: Elsevier Saunders; 2008:chap ...

  18. Periventricular heterotopia and white matter abnormalities in a girl with mosaic ring chromosome 6.

    Science.gov (United States)

    Nishigaki, Satsuki; Hamazaki, Takashi; Saito, Mika; Yamamoto, Toshiyuki; Seto, Toshiyuki; Shintaku, Haruo

    2015-01-01

    Ring chromosome 6 is a rare chromosome abnormality that arises typically de novo. The phenotypes can be highly variable, ranging from almost normal to severe malformations and neurological defects. We report a case of a 3-year-old girl with mosaic ring chromosome 6 who presented with being small for gestational age and intellectual disability, and whose brain MRI later revealed periventricular heterotopia and white matter abnormalities. Mosaicism was identified in peripheral blood cells examined by standard G-bands, mos 46,XX,r(6)(p25q27)[67]/45,XX,-6[25]/46,XX,dic r(6:6)(p25q27:p25q27)[6]/47,XX,r(6)(p25q27) × 2[2]. Using array-comparative genomic hybridization, we identified terminal deletion of 6q27 (1.5 Mb) and no deletion on 6p. To our knowledge, this is the first report of periventricular heterotopia and white matter abnormalities manifested in a patient with ring chromosome 6. These central nervous system malformations are further discussed in relation to molecular genetics.

  19. White Matter Loss in a Mouse Model of Periventricular Leukomalacia Is Rescued by Trophic Factors

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    Pierre Gressens

    2013-11-01

    Full Text Available Periventricular leukomalacia (PVL is the most frequent cause of cerebral palsy and other intellectual disabilities, and currently there is no treatment. In PVL, glutamate excitotoxicity (GME leads to abnormal oligodendrocytes (OLs, myelin deficiency, and ventriculomegaly. We have previously identified that the combination of transferrin and insulin growth factors (TSC1 promotes endogenous OL regeneration and remyelination in the postnatal and adult rodent brain. Here, we produced a periventricular white matter lesion with a single intracerebral injection of N-methyl-d-aspartate (NMDA. Comparing lesions produced by NMDA alone and those produced by NMDA + TSC1 we found that: NMDA affected survival and reduced migration of OL progenitors (OLPs. In contrast, mice injected with NMDA + TSC1 proliferated twice as much indicating that TSC1 supported regeneration of the OLP population after the insult. Olig2-mRNA expression showed 52% OLP survival in mice receiving a NMDA injection and increased to 78% when TSC1 + NMDA were injected simultaneously and ventricular size was reduced by TSC1. Furthermore, in striatal slices TSC1 reduced the inward currents induced by NMDA in medium-sized spiny neurons, demonstrating neuroprotection. Thus, white matter loss after excitotoxicity can be partially rescued as TSC1 conferred neuroprotection to preexisting OLP and regeneration via OLP proliferation. Furthermore, we showed that early TSC1 administration maximizes neuroprotection.

  20. Defective motion processing in children with cerebral visual impairment due to periventricular white matter damage.

    Science.gov (United States)

    Weinstein, Joel M; Gilmore, Rick O; Shaikh, Sumera M; Kunselman, Allen R; Trescher, William V; Tashima, Lauren M; Boltz, Marianne E; McAuliffe, Matthew B; Cheung, Albert; Fesi, Jeremy D

    2012-07-01

    We sought to characterize visual motion processing in children with cerebral visual impairment (CVI) due to periventricular white matter damage caused by either hydrocephalus (eight individuals) or periventricular leukomalacia (PVL) associated with prematurity (11 individuals). Using steady-state visually evoked potentials (ssVEP), we measured cortical activity related to motion processing for two distinct types of visual stimuli: 'local' motion patterns thought to activate mainly primary visual cortex (V1), and 'global' or coherent patterns thought to activate higher cortical visual association areas (V3, V5, etc.). We studied three groups of children: (1) 19 children with CVI (mean age 9y 6mo [SD 3y 8mo]; 9 male; 10 female); (2) 40 neurologically and visually normal comparison children (mean age 9y 6mo [SD 3y 1mo]; 18 male; 22 female); and (3) because strabismus and amblyopia are common in children with CVI, a group of 41 children without neurological problems who had visual deficits due to amblyopia and/or strabismus (mean age 7y 8mo [SD 2y 8mo]; 28 male; 13 female). We found that the processing of global as opposed to local motion was preferentially impaired in individuals with CVI, especially for slower target velocities (p=0.028). Motion processing is impaired in children with CVI. ssVEP may provide useful and objective information about the development of higher visual function in children at risk for CVI. © The Authors. Journal compilation © Mac Keith Press 2011.

  1. Dietary sugars, not lipids, drive hypothalamic inflammation

    OpenAIRE

    Gao, Yuanqing; Bielohuby, Maximilian; Fleming, Thomas; Grabner, Gernot F.; Foppen, Ewout; Bernhard, Wagner; Guzm?n-Ruiz, Mara; Layritz, Clarita; Legutko, Beata; Zinser, Erwin; Garc?a-C?ceres, Cristina; Buijs, Ruud M.; Woods, Stephen C.; Kalsbeek, Andries; Seeley, Randy J.

    2017-01-01

    Objective: The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase of microglial reactivity and its associated cytokine production. However, the role of dietary components, in particular fat and carbohydrate, with respect to the hypothalamic inflammatory response and the consequent impact on hypothalamic control of energy homeostasis is yet not clear. Methods: We dissected the different effects of high-carbohydrate high-fat (HCHF) diets and low-car...

  2. A genetic basis for functional hypothalamic amenorrhea.

    OpenAIRE

    Caronia, L.M.; Martin, C.; Welt, C.K.; Sykiotis, G.P.; Quinton, R.; Thambundit, A.; Avbelj, M.; Dhruvakumar, S.; Plummer, L.; Hughes, V.A.; Seminara, S.B.; Boepple, P.A.; Sidis, Y.; Crowley, W.F.; Martin, K.A.

    2011-01-01

    Background: Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogon...

  3. Bilateral Periventricular Nodular Heterotopia and Lissencephaly in an Infant with Unbalanced t(12;17)(q24.31; p13.3) Translocation

    Science.gov (United States)

    Grosso, Salvatore; Fichera, Marco; Galesi, Ornella; Luciano, Daniela; Pucci, Lucia; Giardini, Francesca; Berardi, Rosario; Balestri, Paolo

    2008-01-01

    Periventricular nodular heterotopia and Miller-Dieker syndrome are two different disorders of brain development. Miller-Dieker syndrome exhibits classical lissencephaly and is related to defects in the lissencephaly gene ("LIS1"). Periventricular nodular heterotopia is characterized by aggregates of grey matter adjacent to the lateral ventricle…

  4. A Genetic Basis for Functional Hypothalamic Amenorrhea

    Science.gov (United States)

    Caronia, Lisa M.; Martin, Cecilia; Welt, Corrine K.; Sykiotis, Gerasimos P.; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A.; Seminara, Stephanie B.; Boepple, Paul A.; Sidis, Yisrael; Crowley, William F.; Martin, Kathryn A.; Hall, Janet E.; Pitteloud, Nelly

    2011-01-01

    BACKGROUND Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. METHODS We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. RESULTS Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kall-mann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. CONCLUSIONS Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.) PMID:21247312

  5. A genetic basis for functional hypothalamic amenorrhea.

    Science.gov (United States)

    Caronia, Lisa M; Martin, Cecilia; Welt, Corrine K; Sykiotis, Gerasimos P; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A; Seminara, Stephanie B; Boepple, Paul A; Sidis, Yisrael; Crowley, William F; Martin, Kathryn A; Hall, Janet E; Pitteloud, Nelly

    2011-01-20

    Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kallmann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.).

  6. Significance of periventricular hyperintensity in T2 weighted MRI on memory dysfunction and depression after stroke

    International Nuclear Information System (INIS)

    Bokura, Hirokazu; Kobayashi, Shotai; Yamaguchi, Shuhei; Yamashita, Kazuya; Koide, Hiromi

    1994-01-01

    We studied the effect of periventricular hyperintensity (PVH) in T2 weighted MRI on memory function and post-stroke depression in 159 patients with cerebrovacular disease. Memory function was assessed with Hasegawa's scale, and depressive state was estimated with Zung's self-rating depression scale. Patients showing diffusely distributed PVH had significantly low scores in memory function tests. Localized PVH around the anterior horns of the laterals ventricle was also associated with impaired memory function when the area of PVH was large. The incidence of post-stroke depression was high in patients with large PVH around the anterior horn in comparison with patients with PVH around the posterior horn. The severity of PVH around the posterior horn did not affect memory function and post-stroke depression. These findings suggest that memory dysfunction and post-stroke depression were accelerated by the diffusely or anteriorly distributed PVH. (author)

  7. Periventricular heterotopia in a boy with interstitial deletion of chromosome 4p.

    Science.gov (United States)

    Gawlik-Kuklinska, Katarzyna; Wierzba, Jolanta; Wozniak, Agnieszka; Iliszko, Mariola; Debiec-Rychter, Maria; Dubaniewicz-Wybieralska, Miroslawa; Limon, Janusz

    2008-01-01

    We report on a 4-year-old boy with a proximal interstitial deletion in the short arm of chromosome 4p with the karyotype 46,XY,del(4)(p14p15.32),inv(9)(p13q13). For a precise delineation of the deleted region, an array-based comparative genomic hybridization (a-CGH) analysis was performed. The proband's phenotype and cytogenetic findings are compared with previously reported cases with proximal 4p deletion syndrome. The syndrome is associated with normal growth, varying degrees of mental retardation, characteristic facial appearance and minor dysmorphic features. Additionally, our patient developed a seizure disorder due to abnormal neuronal migration, i.e., periventricular heterotopia.

  8. Age-related changes in volumes of the ventricles, sulci and periventricular hyperintensity area

    International Nuclear Information System (INIS)

    Yamada, Kenji; Matsuzawa, Taiju; Ono, Shuichi; Kawashima, Ryuta; Matsui, Hiroshige; Yamada, Susumu; Hishinuma, Takashi

    1987-01-01

    Brain atrophy in 47 subjects without neurologic disturbances, ranging in age from 46 to 82 years, was studied using magnetic resonance imaging (MRI). Moreover, the association of the periventricular hyperintensity area (PVH) recognized with MRI, was also investigated. The volume percentages of the brain, the ventricles and sulci to cranial cavity were calculated as indicators of brain atrophy. The brain volume index decreased and the indeces of the ventricles and sulci linearly increased with age, significantly. The volume ratio of the ventricles to sulci significantly increased with increasing age (p < 0.01) and the correlation coefficient was 0.38. This ratio showed negative correlation to the brain volume index. The volume percentage of PVH to the cranial cavity started to increase in the sixties and negatively correlated with the brain volume index. There was positive correlation between the ratio of the ventricles to sulci and the index of PVH. (author)

  9. A postmortem correlation of computer tomography and ultrasound scans of periventricular hemorrhage in preterm infants

    International Nuclear Information System (INIS)

    Fukuda, Seiichi; Hashimoto, Takeo; Yamashita, Yushiro; Nishimi, Toshihiro; Utsunomiya, Hidetsuna; Nakamura, Yasuhiro; Okudera, Toshio

    1988-01-01

    From January 1984 through September 1987, ultrasound scanning (US), computed tomography (CT), and autopy have been performed in 80 consecutive premature infants. Intracranial lesions consisted of intraventricular hemorrhage (IVH, n = 61), subarachnoid hemorrhage (SAH, n = 63), cerebellar hemorrhage (n = 5), hydrocephalus (n = 8), periventricular leukoencephalomalacia (n = 20), and anoxic encephalopathy (n = 40). Using autopsy findings as the standard, both US and CT had an accuracy of 80 % or more in detecting subependymal hemorrhage (SEH), IVH, dilated ventricle, and parenchymal hemorrhage ; however, both imaging modalities showed a high false negative for SAH (77 % for US vs 55 % for CT). Accuracy of US and CT was 82 % vs 72 % for SEH, and 72 % vs 85 % for IVH. High false positive and false negative rates, in spite of 80 % or more accuracy of imaging modalities, warrant further studies to obtain higher accuracy in the diagnosis of intracranial lesions. (Namekawa, K.)

  10. Postmortem correlation of computer tomography and ultrasound scans of periventricular hemorrhage in preterm infants

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Seiichi; Hashimoto, Takeo; Yamashita, Yushiro; Nishimi, Toshihiro; Utsunomiya, Hidetsuna; Nakamura, Yasuhiro; Okudera, Toshio

    1988-08-01

    From January 1984 through September 1987, ultrasound scanning (US), computed tomography (CT), and autopy have been performed in 80 consecutive premature infants. Intracranial lesions consisted of intraventricular hemorrhage (IVH, n = 61), subarachnoid hemorrhage (SAH, n = 63), cerebellar hemorrhage (n = 5), hydrocephalus (n = 8), periventricular leukoencephalomalacia (n = 20), and anoxic encephalopathy (n = 40). Using autopsy findings as the standard, both US and CT had an accuracy of 80 % or more in detecting subependymal hemorrhage (SEH), IVH, dilated ventricle, and parenchymal hemorrhage ; however, both imaging modalities showed a high false negative for SAH (77 % for US vs 55 % for CT). Accuracy of US and CT was 82 % vs 72 % for SEH, and 72 % vs 85 % for IVH. High false positive and false negative rates, in spite of 80 % or more accuracy of imaging modalities, warrant further studies to obtain higher accuracy in the diagnosis of intracranial lesions. (Namekawa, K.).

  11. Hypothalamic dysfunction following whole-brain irradiation

    International Nuclear Information System (INIS)

    Mechanick, J.I.; Hochberg, F.H.; LaRocque, A.

    1986-01-01

    The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage

  12. Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy.

    Science.gov (United States)

    Fallil, Zianka; Pardoe, Heath; Bachman, Robert; Cunningham, Benjamin; Parulkar, Isha; Shain, Catherine; Poduri, Annapurna; Knowlton, Robert; Kuzniecky, Ruben

    2015-10-01

    Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue. Copyright © 2015 Elsevier Inc. All

  13. Efferent connections from the lateral hypothalamic region and the lateral preoptic area to the hypothalamic paraventricular nucleus of the rat

    DEFF Research Database (Denmark)

    Larsen, P J; Hay-Schmidt, Anders; Mikkelsen, J D

    1994-01-01

    , iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were delivered into distinct areas of the lateral hypothalamic region. Neurons of the intermediate hypothalamic area projected mainly to the PVN subnuclei, which contained parvicellular neuroendocrine cells. In contrast...

  14. Role of developmental factors in hypothalamic function

    Directory of Open Access Journals (Sweden)

    Jakob eBiran

    2015-04-01

    Full Text Available The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing distinct neuronal populations producing neuropeptides and neurotransmitters that regulate fundamental body functions including temperature and metabolic rate, thirst and hunger, sexual behavior and reproduction, circadian rhythm, and emotional responses. The identity, number and connectivity of these neuronal populations are established during the organism’s development and are of crucial importance for normal hypothalamic function. Studies have suggested that developmental abnormalities in specific hypothalamic circuits can lead to obesity, sleep disorders, anxiety, depression and autism. At the molecular level, the development of the hypothalamus is regulated by transcription factors, secreted growth factors, neuropeptides and their receptors. Recent studies in zebrafish and mouse have demonstrated that some of these molecules maintain their expression in the adult brain and subsequently play a role in the physiological functions that are regulated by hypothalamic neurons. Here, we summarize the involvement of some of the key developmental factors in hypothalamic development and function by focusing on the mouse and zebrafish genetic model organisms.

  15. Sexual behavior reduces hypothalamic androgen receptor immunoreactivity

    NARCIS (Netherlands)

    Fernandez-Guasti, Alonso; Swaab, Dick; Rodríguez-Manzo, Gabriela

    2003-01-01

    Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express

  16. Hypothalamic functions in patients with pituitary insufficiency

    NARCIS (Netherlands)

    Borgers, A.J.F.

    2013-01-01

    The main objective of this thesis is to increase our understanding of hypothalamic (dys)function in patients with pituitary insufficiency. This goal is driven by the clinical experience of persisting symptoms in patients adequately treated for pituitary insufficiency. We focus primarily on patients

  17. Evolution of Gelastic Epilepsy with Hypothalamic Hamartoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available The patterns of clinical presentation, evolution of the epilepsy, and electoclinical diagnostic features of hypothalamic hamartoma (HH in 19 patients (8 children and 11 adults, seen between 1991 and 2001, were evaluated at Kings College Hospital and the Institute of Epileptology, London, UK.

  18. Dietary sugars, not lipids, drive hypothalamic inflammation

    NARCIS (Netherlands)

    Gao, Yuanqing; Bielohuby, Maximilian; Fleming, Thomas; Grabner, Gernot F; Foppen, Ewout; Bernhard, Wagner; Guzmán-Ruiz, Mara; Layritz, Clarita; Legutko, Beata; Zinser, Erwin; García-Cáceres, Cristina; Buijs, Ruud M; Woods, Stephen C; Kalsbeek, A.; Seeley, Randy J; Nawroth, Peter P; Bidlingmaier, Martin; Tschöp, Matthias H; Yi, Chun-Xia

    OBJECTIVE: The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase of microglial reactivity and its associated cytokine production. However, the role of dietary components, in particular fat and carbohydrate, with respect to the hypothalamic inflammatory

  19. Dietary sugars, not lipids, drive hypothalamic inflammation

    NARCIS (Netherlands)

    Gao, Yuanqing; Bielohuby, Maximilian; Fleming, Thomas; Grabner, Gernot F.; Foppen, Ewout; Bernhard, Wagner; Guzmán-Ruiz, Mara; Layritz, Clarita; Legutko, Beata; Zinser, Erwin; García-Cáceres, Cristina; Buijs, Ruud M.; Woods, Stephen C.; Kalsbeek, Andries; Seeley, Randy J.; Nawroth, Peter P.; Bidlingmaier, Martin; Tschöp, Matthias H.; Yi, Chun-Xia

    2017-01-01

    Objective: The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase of microglial reactivity and its associated cytokine production. However, the role of dietary components, in particular fat and carbohydrate, with respect to the hypothalamic inflammatory

  20. Flatfish metamorphosis: a hypothalamic independent process?

    Science.gov (United States)

    Campinho, Marco A; Silva, Nadia; Roman-Padilla, Javier; Ponce, Marian; Manchado, Manuel; Power, Deborah M

    2015-03-15

    Anuran and flatfish metamorphosis are tightly regulated by thyroid hormones that are the necessary and sufficient factors that drive this developmental event. In the present study whole mount in situ hybridization (WISH) and quantitative PCR in sole are used to explore the central regulation of flatfish metamorphosis. Central regulation of the thyroid in vertebrates is mediated by the hypothalamus-pituitary-thyroid (HPT) axis. Teleosts diverge from other vertebrates as hypothalamic regulation in the HPT axis is proposed to be through hypothalamic inhibition although the regulatory factor remains enigmatic. The dynamics of the HPT axis during sole metamorphosis revealed integration between the activity of the thyrotrophes in the pituitary and the thyroid follicles. No evidence was found supporting a role for thyroid releasing hormone (trh) or corticotrophin releasing hormone (crh) in hypothalamic control of TH production during sole metamorphosis. Intriguingly the results of the present study suggest that neither hypothalamic trh nor crh expression changes during sole metamorphosis and raises questions about the role of these factors and the hypothalamus in regulation of thyrotrophs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Hyperprolactinemia from radiation-induced hypothalamic hypopituitarism

    International Nuclear Information System (INIS)

    Corkill, G.; Hanson, F.W.; Gold, E.M.; White, V.A.

    1980-01-01

    In 1975 Samaan et al., described the effects of radiation damage of the hypothalamus in 15 patients with head and neck cancer. Shalet et al., in 1977 described endocrine morbidity in adults who as children had been irradiated for brain tumors. This report describes instances of hyperprolactinemia and associated hypothalamic, pituitary, and thyroid dysfunction following irradiation of a young adult female for brain neoplasia

  2. Clinical features and long term outcome of epilepsy in periventricular nodular heterotopia. Simple compared with plus forms

    Science.gov (United States)

    d'Orsi, G; Tinuper, P; Bisulli, F; Zaniboni, A; Bernardi, B; Rubboli, G; Riva, R; Michelucci, R; Volpi, L; Tassinari, C; Baruzzi, A

    2004-01-01

    Objectives: Little is known about the long term outcome of patients with periventricular nodular heterotopia (PNH) and epilepsy, particularly the course of seizures. This study investigated the electroclinical and prognostic features of 16 patients with PNH. Methods: Of 120 patients with epilepsy and malformations of cortical development, 16 had PNH. Of these, eight patients had periventricular nodules only (simple PNH) and eight also presented with other cortical or cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia; schizencephaly; cortical infolding; agenesis of the corpus callosum; mega cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3 years (2–40 years). Results: Two electroclinical patterns emerged: (1) The first pattern, associated with simple PNH, was characterised by normal intelligence and seizures, usually partial, which began during the second decade of life. The seizures never became frequent and tended to disappear or become very rare. The EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus, was characterised by mental retardation and seizures that began during the first decade of life. The seizures were very frequent in most cases and sudden drops were observed in six patients. Seizures were medically refractory in four patients. The EEG showed focal and bisynchronous abnormalities. Conclusions: Two groups of PNH patients with different electroclinical and neuroradiological features can be identified after a long term follow up. The presence of other types of cortical or cerebral malformations, in addition to periventricular nodules, determines a poor prognosis. PMID:15146004

  3. Diffuse periventricular leukomalacia in preterm children: assessment of grey matter changes by MRI

    International Nuclear Information System (INIS)

    Tzarouchi, L.C.; Xydis, V.; Zikou, A.K.; Papastefanaki, M.; Argyropoulou, Maria I.; Drougia, A.; Andronikou, S.; Astrakas, L.G.

    2011-01-01

    Preterm children may have cognitive deficits and behavioural disorders suggestive of grey matter (GM) injury. The prevalence is higher in preterm children with diffuse periventricular leukomalacia (dPVL). Evaluate changes in the volume of 116 GM areas in preterm children with dPVL. Eleven preterm children with dPVL, gestational age 32.8 ± 2.6 weeks, examined at corrected age 22.0 ± 18.2 months and 33 matched preterm controls with normal brain MRI were studied. Volumes of 116 individual GM areas, and white matter/cerebrospinal fluid (WM/CSF) ratio were calculated on T1-weighted high-resolution images after segmentation. Relative to controls, children with dPVL had decreased GM volume of the hippocampus, amygdala, and frontal lobes and temporal middle gyrus (P < 0.05); increased GM volume of the putamen, thalamus, globus pallidum, superior temporal gyrus and of the parietal and occipital lobes (P < 0.05) and lower WM volume/higher CSF volume (P < 0.05). WM/CSF ratios also differed (P < 0.05). Preterm children with dPVL have increased regional GM volume in some areas probably related with a process of brain plasticity-regeneration and reduced GM volume in areas associated with cognition and memory. (orig.)

  4. Diffuse periventricular leukomalacia in preterm children: assessment of grey matter changes by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Tzarouchi, L.C.; Xydis, V.; Zikou, A.K.; Papastefanaki, M.; Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Drougia, A.; Andronikou, S. [University of Ioannina, Neonatal Intensive Care Unit, Child Health Department, Medical School, Ioannina (Greece); Astrakas, L.G. [University of Ioannina, Department of Medical Physics, Medical School, Ioannina (Greece)

    2011-12-15

    Preterm children may have cognitive deficits and behavioural disorders suggestive of grey matter (GM) injury. The prevalence is higher in preterm children with diffuse periventricular leukomalacia (dPVL). Evaluate changes in the volume of 116 GM areas in preterm children with dPVL. Eleven preterm children with dPVL, gestational age 32.8 {+-} 2.6 weeks, examined at corrected age 22.0 {+-} 18.2 months and 33 matched preterm controls with normal brain MRI were studied. Volumes of 116 individual GM areas, and white matter/cerebrospinal fluid (WM/CSF) ratio were calculated on T1-weighted high-resolution images after segmentation. Relative to controls, children with dPVL had decreased GM volume of the hippocampus, amygdala, and frontal lobes and temporal middle gyrus (P < 0.05); increased GM volume of the putamen, thalamus, globus pallidum, superior temporal gyrus and of the parietal and occipital lobes (P < 0.05) and lower WM volume/higher CSF volume (P < 0.05). WM/CSF ratios also differed (P < 0.05). Preterm children with dPVL have increased regional GM volume in some areas probably related with a process of brain plasticity-regeneration and reduced GM volume in areas associated with cognition and memory. (orig.)

  5. Magnetic resonance and cranial ultrasound characteristics of periventricular white matter abnormalities in newborn infants

    International Nuclear Information System (INIS)

    Childs, Anne-Marie; Cornette, Luc; Ramenghi, Luca A.; Tanner, Steven F.; Arthur, Rosemary J.; Martinez, Delia; Levene, Malcolm I.

    2001-01-01

    OBJECTIVE: To characterize the range of abnormalities within the periventricular white matter (PVWM) in a cohort of newborns using magnetic resonance (MR) brain imaging and to compare the focal MR abnormalities with the cranial ultrasound (CUS) findings. METHODS: Retrospective study of MR brain and CUS findings of infants born in the 18-month period 1998-1999. PVWM abnormalities were identified by MR and focal lesions were characterized by size, number and distribution using a grading scale. Correspondence with CUS findings was assessed. RESULTS: 175 MR examinations corresponding to n = 105 preterm infants, (median GA 28, range 23-36 weeks) and n = 25 term infants (median GA 39, range 37-42 weeks) were analysed for PVWM abnormalities. In the preterm group, MR demonstrated a normal PVWM in n = 76, focal areas of altered signal intensity (SI) in PVWM in n = 26 and venous infarction inn 3. In the term group, MR demonstrated a normal PVWM in n = 15, focal areas of altered SI in PVWM in n = 4, oedematous PVWM in n = 2 and a middle cerebral artery infarction in n = 4. All infants with normal MR had normal CUS findings. A focal PVWM SI abnormality detectable on MR corresponded with an abnormality on CUS in only n = 10/30. CONCLUSIONS: MR appears considerably more sensitive than CUS in demonstrating the existence and extent of focal PVWM lesions in newborn infants. Satisfactory correspondence between the two imaging investigations is obtained only for cystic PVWM lesions. Childs, A.-M. et al. (2001)

  6. Multicentre trial of ethamsylate for prevention of periventricular haemorrhage in very low birthweight infants.

    Science.gov (United States)

    Benson, J W; Drayton, M R; Hayward, C; Murphy, J F; Osborne, J P; Rennie, J M; Schulte, J F; Speidel, B D; Cooke, R W

    1986-12-06

    The effectiveness of ethamsylate in the prevention of periventricular haemorrhage (PVH) in very low birthweight infants was evaluated by means of a multicentre, placebo-controlled, double-blind trial. In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage, but intraventricular and parenchymal haemorrhages developed in 30/162 infants (18.5%) in the treated group, compared with 50/168 (29.8%) in the control group (p less than 0.02). The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 (14.6%) in the ethamsylate group and 37/146 (25.3%) in the controls (p less than 0.05). In 30 infants with evidence of PVH on the initial scan, ethamsylate treatment seemed to limit parenchymal extension. Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grades of severity of PVH was recorded during the trial was lower in the treated than in the placebo group (p less than 0.01). No adverse effects were attributed to ethamsylate therapy. The reported incidence of patent ductus arterious was lower in the treated than in the placebo group (p less than 0.02). Mortality was similar in the two groups.

  7. Ethamsylate in the prevention of periventricular-intraventricular hemorrhage in premature infants.

    Science.gov (United States)

    Chen, J Y

    1993-10-01

    A random and controlled trial was conducted to evaluate the efficacy and safety of ethamsylate in the prevention of periventricular-intraventricular hemorrhage (PIVH) in premature infants. Between January 1990 and July 1992, 171 premature infants with a birth weight of ethamsylate 12.5 mg/kg (0.1 mL/kg from 250 mg/2mL ampoules) was given to group 1 intravenously within an hour of delivery and was followed by doses at six-hourly intervals for four days (total dose 200 mg/kg). Group 2 consisted of 85 premature infants with mean birth weight of 1.4 +/- 0.3 kg and mean gestational age of 30.4 +/- 2.2 weeks. Group 2 received 0.1 mL/kg normal saline intravenously in a similar fashion as the ethamsylate-treated group. Cranial ultrasound examinations were performed on postnatal days one, two, three, five, seven and 14. The incidence of PIVH in the ethamsylate-treated group was 24/86 (27.9%) and 39/85 (45.9%) in the control group (p ethamsylate-treated group was 9/86 (10.5%) and 20/85 (23.5%) in the control group (p ethamsylate therapy in this study.

  8. Title: Cytoskeletal proteins in cortical development and diseasesubtitle: Actin associated proteins in periventricular heterotopia

    Directory of Open Access Journals (Sweden)

    Gewei eLian

    2015-04-01

    Full Text Available The actin cytoskeleton regulates many important cellular processes in the brain, including cell division and proliferation, migration, and cytokinesis and differentiation. These developmental processes can be regulated through actin dependent vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape. Many of these processes are mediated by extensive and intimate interactions of actin with cellular membranes and proteins. Disruption in the actin cytoskeleton in the brain gives rise to periventricular heterotopia (PH, a malformation of cortical development, characterized by abnormal neurons clustered deep in the brain along the lateral ventricles. This disorder can give rise to seizures, dyslexia and psychiatric disturbances. Anatomically, PH is characterized by a smaller brain (impaired proliferation, heterotopia (impaired initial migration and disruption along the neuroependymal lining (impaired cell-cell adhesion. Genes causal for PH have also been implicated in actin-dependent processes. The current review provides mechanistic insight into actin cytoskeletal regulation of cortical development in the context of this malformation of cortical development.

  9. Identification of a duplication of Xq28 associated with bilateral periventricular nodular heterotopia.

    Science.gov (United States)

    Fink, J M; Dobyns, W B; Guerrini, R; Hirsch, B A

    1997-01-01

    Bilateral periventricular nodular heterotopia (BPNH) is a malformation of neuronal migration and is characterized by nodules of heterotopic gray matter lining the lateral ventricles of the brain. The majority of BPNH patients are female and have epilepsy as a sole clinical manifestation of their disease. Familial BPNH has been mapped to Xq28 by linkage analysis. A multiple congenital anomaly-mental retardation syndrome (BPNH/MR) was recently delineated in three unrelated boys with BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. High-resolution chromosome analysis revealed a subtle abnormality of Xq28 in one of the boys with BPNH/MR syndrome. FISH with cosmids and YACs from Xq28 further characterized this abnormality as a 2.25-3.25-Mb inverted duplication. No abnormality of Xq28 was detected by G-banding or FISH in the other two boys. These data support the linkage assignment of BPNH to band Xq28 and narrow the critical region to the distal 2.25-3.25 Mb of Xq28. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:9311743

  10. De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.

    Science.gov (United States)

    Heinzen, Erin L; O'Neill, Adam C; Zhu, Xiaolin; Allen, Andrew S; Bahlo, Melanie; Chelly, Jamel; Dobyns, William B; Freytag, Saskia; Guerrini, Renzo; Leventer, Richard J; Poduri, Annapurna; Robertson, Stephen P; Walsh, Christopher A; Zhang, Mengqi

    2018-05-08

    Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome sequenced 202 individuals with sporadic PVNH to identify novel genetic risk loci. We first performed a trio-based analysis and identified 219 de novo variants. Although no novel genes were implicated in this initial analysis, PVNH cases were found overall to have a significant excess of nonsynonymous de novo variants in intolerant genes (p = 3.27x10-7), suggesting a role for rare new alleles in genes yet to be associated with the condition. Using a gene-level collapsing analysis comparing cases and controls, we identified a genome-wide significant signal driven by four ultra-rare loss-of-function heterozygous variants in MAP1B, including one de novo variant. In at least one instance, the MAP1B variant was inherited from a parent with previously undiagnosed PVNH. The PVNH was frontally predominant and associated with perisylvian polymicrogyria. These results implicate MAP1B in PVNH. More broadly, our findings suggest that detrimental mutations likely arising in immediately preceding generations with incomplete penetrance may also be responsible for some apparently sporadic diseases.

  11. Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease

    Directory of Open Access Journals (Sweden)

    Volney L. Sheen

    2012-01-01

    Full Text Available During cortical development, proliferating neural progenitors exhibit polarized apical and basolateral membranes that are maintained by tightly controlled and membrane-specific vesicular trafficking pathways. Disruption of polarity through impaired delivery of proteins can alter cell fate decisions and consequent expansion of the progenitor pool, as well as impact the integrity of the neuroependymal lining. Loss of neuroependymal integrity disrupts radial glial scaffolding and alters initial neuronal migration from the ventricular zone. Vesicle trafficking is also required for maintenance of lipid and protein cycling within the leading and trailing edge of migratory neurons, as well as dendrites and synapses of mature neurons. Defects in this transport machinery disrupt neuronal identity, migration, and connectivity and give rise to a malformation of cortical development termed as periventricular heterotopia (PH. PH is characterized by a reduction in brain size, ectopic clusters of neurons localized along the lateral ventricle, and epilepsy and dyslexia. These anatomical anomalies correlate with developmental impairments in neural progenitor proliferation and specification, migration from loss of neuroependymal integrity and neuronal motility, and aberrant neuronal process extension. Genes causal for PH regulate vesicle-mediated endocytosis along an actin cytoskeletal network. This paper explores the role of these dynamic processes in cortical development and disease.

  12. Intracranial evaluation and laser ablation for epilepsy with periventricular nodular heterotopia.

    Science.gov (United States)

    Thompson, Stephen A; Kalamangalam, Giridhar P; Tandon, Nitin

    2016-10-01

    Surgical treatment of focal epilepsy in the presence of periventricular nodular heterotopia (PVNH) poses a challenge, as the relative roles of the nodular tissue and the overlying cortex in the generation of seizures can be complex and variable. Here, we review the literature on chronic invasive EEG recordings in humans with this substrate and present two illustrative cases from our practice. We found that while inter-ictal spiking from nodules is common, clinical seizures rarely arise solely from nodular tissue. More typically, ictal onset is simultaneous with overlying neocortex or mesial temporal structures. Surgical outcome is more favorable in cases with unilateral (as opposed to bilateral) PVNH, and when a substantial or complete ablation of PVNH is performed. In rare cases, nodular ablation alone may be sufficient, as may be completed by MRI-guided laser interstitial thermal therapy. The mechanism(s) by which PNVH interacts with overlying cortex are not fully understood, but we suggest that PVNH either orchestrates or amplifies local network epileptogenicity. At present, invasive recordings with penetrating depth electrodes are required prior to surgical therapy, as illustrated in our cases. Published by Elsevier Ltd.

  13. Periventricular nodular heterotopia in patients with filamin-1 gene mutations: neuroimaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, T.Y. [Dept. of Radiology, Children' s Hospital, Boston, MA (United States); Fox, J.W.; Walsh, C.A. [Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA (United States); Dept. of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA (United States); Dobyns, W.B. [Department of Human Genetics, The University of Chicago, Chicago, IL (United States); Radtke, R. [Division of Neurology, Duke University Medical Center, Durham, NC (United States); Scheffer, I.E.; Berkovic, S.F. [Department of Neurology, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg (Australia); Barnes, P.D. [Department of Radiology, Children' s Hospital and Harvard Medical School, Boston, MA (United States); Huttenlocher, P.R. [Department of Pediatrics, University of Chicago, Chicago, Illinois (United States)

    2000-11-01

    Background. The filamin-1 (FLN-1) gene is responsible for periventricular nodular heterotopia (PNH), which is an X-linked dominant neuronal migration disorder. Objective. To review the clinical and imaging findings in a series of patients with documented filamin-1 mutations. Materials and methods. A retrospective review of the medical records and MR studies of a series of patients with PNH and confirmed FLN-1 mutations was done. There were 16 female patients (age range:.67-71 years; mean = 28.6) with filamin-1 gene mutations. Results. In six of the patients the same mutation was inherited in four generations in one pedigree. In a second pedigree, a distinct mutation was found in two patients in two generations. In a third pedigree, a third mutation was found in four patients in two generations. The remaining four patients had sporadic de novo mutations that were not present in the parents. Ten patients had seizures, and all patients had normal intelligence. In all 16 patients MR demonstrated bilateral near-continuous PNH. There were no consistent radiographic or clinical differences between patients carrying different mutations. Conclusion. Patients with confirmed FLN-1 gene mutations are usually female and have a distinctive MR pattern of PNH. Other female patients with this same MR pattern probably harbor FLN-1 mutations and risk transmission to their progeny. This information is important for genetic counseling. (orig.)

  14. Periventricular nodular heterotopia in patients with filamin-1 gene mutations: neuroimaging findings

    International Nuclear Information System (INIS)

    Poussaint, T.Y.; Fox, J.W.; Walsh, C.A.; Dobyns, W.B.; Radtke, R.; Scheffer, I.E.; Berkovic, S.F.; Barnes, P.D.; Huttenlocher, P.R.

    2000-01-01

    Background. The filamin-1 (FLN-1) gene is responsible for periventricular nodular heterotopia (PNH), which is an X-linked dominant neuronal migration disorder. Objective. To review the clinical and imaging findings in a series of patients with documented filamin-1 mutations. Materials and methods. A retrospective review of the medical records and MR studies of a series of patients with PNH and confirmed FLN-1 mutations was done. There were 16 female patients (age range:.67-71 years; mean = 28.6) with filamin-1 gene mutations. Results. In six of the patients the same mutation was inherited in four generations in one pedigree. In a second pedigree, a distinct mutation was found in two patients in two generations. In a third pedigree, a third mutation was found in four patients in two generations. The remaining four patients had sporadic de novo mutations that were not present in the parents. Ten patients had seizures, and all patients had normal intelligence. In all 16 patients MR demonstrated bilateral near-continuous PNH. There were no consistent radiographic or clinical differences between patients carrying different mutations. Conclusion. Patients with confirmed FLN-1 gene mutations are usually female and have a distinctive MR pattern of PNH. Other female patients with this same MR pattern probably harbor FLN-1 mutations and risk transmission to their progeny. This information is important for genetic counseling. (orig.)

  15. Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

    Science.gov (United States)

    Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

    2013-06-01

    Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. Copyright © 2013 Wiley Periodicals, Inc.

  16. Ehlers-Danlos syndrome: a cause of epilepsy and periventricular heterotopia.

    Science.gov (United States)

    Verrotti, Alberto; Monacelli, Debora; Castagnino, Miriam; Villa, Maria Pia; Parisi, Pasquale

    2014-11-01

    Ehlers-Danlos syndrome (EDS) comprises a variety of inherited connective tissue disorders that have been described in association with various neurological features. Until now the neurological symptoms have not been studied in detail; therefore, the aim of this review is to analyze the possible association between EDS, epilepsy and periventricular heterotopia (PH). We have carried out a critical review of all cases of epilepsy in EDS patients with and without PH. Epilepsy is a frequent neurological manifestation of EDS; generally, it is characterized by focal seizures with temporo-parieto-occipital auras and the most common EEG findings epileptiform discharges and slow intermittent rhythm with delta-theta waves. Epilepsy in EDS patients is usually responsive to common antiepileptic therapy; very few cases of drug resistant focal epilepsy requested surgical treatment, with favorable results in terms of outcome. Epilepsy is the most common presenting neurological manifestation associated with PH in EDS patients. Abnormal anatomic circuitries (including heterotopic nodules) could generate epilepsy in patients with PH. Among the principal neurological manifestations, epilepsy and PH have a considerable importance and can influence the long-term evolution of these patients. We hypothesize that PH may determine the epileptic manifestations in patients with EDS; much remains to be learnt about the relationships between nodules and the epileptic manifestations in EDS syndrome. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  17. Reading of kana (phonetic symbols for syllables) in Japanese children with spastic diplegia and periventricular leukomalacia.

    Science.gov (United States)

    Yokochi, K

    2000-01-01

    In 31 Japanese children with spastic diplegia and periventricular leukomalacia (PVL), the age at which they could read Hiragana (phonetic symbols for syllables) and psychometric data were examined. Reading of Hiragana was achieved between 2 and 8 years of age in all subjects except one. Four children could read Hiragana at 2 to 3 years of age, an age which is considered early among Japanese children. Performance IQs of the Wechsler Scale were lower than Verbal IQs in 18 of 19 children who were administered this test, and DQs of the cognitive adaptive (C-A) area of the K-form developmental test (a popular test in Japan) were lower than those of the language social area in all 12 children taking this test. Among eight children having performance IQs or DQs of C-A less than 50, seven acquired reading ability of Hiragana at 8 years of age or below. A visuoperceptual disorder manifested by diplegic children with PVL does not affect the acquisition of Kana-reading ability.

  18. Etiologic evaluation of periventricular hyperintensity in MR images of first-ever cerebral thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Iwamoto, Toshihiko; Enomoto, Mutsurou; Ogawa, Kimikazu; Yanagawa, Kiyotaka; Takasaki, Masaru [Tokyo Medical Coll. (Japan)

    1995-02-01

    To clarify the etiology of periventricular hyperintensity (PVH) seen on magnetic resonance (MR) images (especially on T2-weighted images), PVH was investigated in relation to causative lesions, angiographic findings, and risk factors for cerebrovascular accidents. The subjects were 103 patients with first-ever cerebral thrombosis (thrombosis group). Age-matched 37 patients with hypertension or diabetes mellitus (risk group) and 78 other patients with neither stroke nor any risk factor served as controls. MR imaging and angiography were undertaken within 3 months after the onset of stroke. Causative lesions were confined to the cerebral cortex (CR type, n=25), centrum semiovale (CS type, n=10), internal capsule/corona radiata (IC/CR type, n=46), and brainstem/cerebellum (BS type, n=22). PVH was classified into none, rims/caps, patchy, and diffuse. Patchy and diffuse types were significantly more common in the thrombosis group and the risk group of hypertensive patients than the other control patients. Diffuse type PVH coexisted with stenosed major cerebral artery and CS type infarction. In contrast, patchy PVH was closely correlated with IC/CR infarction caused by lesions of the perforating artery. These findings suggest that hemodynamic changes caused by large vessel diseases may result in diffuse PVH, while patchy PVH was confluent with multiple lesions induced by small vessel diseases. (N.K.).

  19. Sepse neonatal como fator de risco para leucomalácia periventricular em pré-termos de muito baixo peso Periventricular leukomalacia in very low birth weight preterm neonates with high risk for neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Rita C. Silveira

    2008-06-01

    Full Text Available OBJETIVO: Verificar a associação de leucomalácia periventricular (LPV e sepse neonatal em recém-nascidos de muito baixo peso (RNMBP. MÉTODOS: Foram incluídos RNMBP com suspeita clínica de infecção nascidos na instituição de 01/08/2005 a 31/07/2007. Foram excluídos óbitos antes dos 14 dias, malformações do sistema nervoso central e infecções congênitas. Foi realizado ultra-som cerebral no terceiro dia e semanalmente até a sexta semana de vida ou alta. LPV foi diagnosticada por hiperecogenicidade difusa periventricular persistente por mais de 7 dias, ou por cistos periventriculares. RNMBP foram divididos em grupos com e sem LPV. Sepse foi definida por manifestação clínica com cultura positiva. Os testes t, Mann-Whitney, qui-quadrado e regressão logística foram usados. RESULTADOS: Foram incluídos 88 RNMBP, sendo que 62 (70,5% sobreviveram e 51 (57,8% tiveram LPV. Os grupos foram semelhantes no peso de nascimento, idade gestacional, escore de Apgar, tipo de parto, SNAPPE-II, presenças de enterocolite necrosante, persistência de canal arterial e óbitos. Sepse e ventilação mecânica foram mais freqüentes no grupo com LPV (23,5 e 2,7%, p = 0,005; 86 e 59%, p = 0,004, respectivamente. Na regressão logística, ambos foram fatores de risco independentes para LPV (p = 0,027 e 0,015, respectivamente. CONCLUSÃO: Corioamnionite é fator de risco definido para LPV. Demonstramos que sepse neonatal também é fator de risco importante. Acreditamos que a resposta inflamatória sistêmica seja o principal fator envolvido na etiopatogenia da LPV em RNMBP.OBJECTIVE: To investigate the association between periventricular leukomalacia (PVL and neonatal sepsis in very low birth weight infants (VLBWI. METHODS: We studied VLBWI with a clinical suspicion of infection who had been born at our institution between the 1st of August, 2005 and the 31st of July, 2007. Children were excluded if they died before reaching 14 days, had malformations

  20. Paraneoplastic limbic encephalitis with associated hypothalamitis mimicking a hyperdense hypothalamic tumor: a case report

    International Nuclear Information System (INIS)

    Bataduwaarachchi, Vipula R.; Tissera, Nirmali

    2016-01-01

    Paraneoplastic limbic encephalitis is an uncommon association of common malignancies such as small cell lung carcinoma, testicular teratoma, and breast carcinoma. The nonspecific nature of the clinical presentation, lack of freely available diagnostic markers, and requirement for advanced imaging techniques pose a great challenge in the diagnosis of this disease in resource-poor settings. A 64-year-old previously healthy Sri Lankan man was admitted to the general medical unit with subacute memory impairment regarding recent events that had occurred during the previous 3 weeks. Initial noncontrast computed tomography of the brain revealed a hyperdensity in the hypothalamic region surrounded by hypodensities extending toward the bilateral temporal lobes; these findings were consistent with a possible hypothalamic tumor with perilesional edema. The patient later developed cranial diabetes insipidus, which was further suggestive of hypothalamic disease. Interestingly, gadolinium-enhanced magnetic resonance imaging of the brain showed no such lesions; instead, it showed prominent T2-weighted signals in the inner mesial region, characteristic of encephalitis. The possibility of tuberculosis and viral encephalitis was excluded based on cerebrospinal fluid analysis results. Limbic encephalitis with predominant hypothalamitis was suspected based on the radiological pattern. Subsequent screening for underlying malignancy revealed a mass lesion in the right hilum on chest radiographs. Histological examination of the lesion showed small cell lung cancer of the “oat cell” variety. We suggest that the initial appearance of a hyperdensity in the hypothalamus region on noncontrast computed tomography is probably due to hyperemia caused by hypothalamitis. If hypothalamitis is predominant in a patient with paraneoplastic limbic encephalitis, magnetic resonance imaging will help to differentiate it from a hypothalamic secondary deposit. Limbic encephalitis should be considered in

  1. Magnetic resonance imaging of hypothalamic hamartoma

    Energy Technology Data Exchange (ETDEWEB)

    Kanazawa, Junichi; Uozumi, Tohru; Sakoda, Katsuaki; Yamanaka, Masami; Kihara, Mikio; Nishi, Yoshikazu; Kagawa, Yoshihiro; Kajima, Toshio.

    1988-05-01

    Magnetic resonance (MR) findings of two patients with a hypothalamic hamartoma are discussed. The two girls showed clinical symptoms and endocrinological signs of precocious puberty. MR imaging was of diagnostic value superior to that of CT in the demonstration of the characteristic location of this tumor and relationships to the neighboring structures because of its multi-dimensional utility. Although it has been reported that CT showed this lesion as isodense to the grey matter with and without injection of contrast medium, MR imaging depicted the lesion as a high signal intensity area on T2-weighted images in both patients. MR imaging is a useful method for the evaluation of the hypothalamic hamartoma.

  2. Lymphocytic hypophysitis and hypothalamitis - a case report

    International Nuclear Information System (INIS)

    Stelmachowska, M.; Bolko, P.; Wasko, R.; Sowinski, J.; Kosinski, D.; Towpik, I.

    2006-01-01

    Lymphocytic hypophysitis is an unusual disorder that nearly exclusively affects women. We present a case of 69 year-old female patient who developed the symptoms of diabetes insipidus and partial insufficiency of the anterior pituitary gland. Magnetic resonance imaging of the brain revealed a mass involving the sella and suprasellar region. After exclusion of other causes of infiltrate in this region and due to evident reaction to glucocorticoid treatment the diagnosis of lymphocytic hypophisitis and hypothalamitis was established. (author)

  3. The role of hypothalamic inflammation, the hypothalamic-pituitary-adrenal axis and serotonin in the cancer anorexia-cachexia syndrome.

    Science.gov (United States)

    van Norren, Klaske; Dwarkasing, Jvalini T; Witkamp, Renger F

    2017-09-01

    In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.

  4. Magnetization transfer imaging of periventricular white matter lesions in patients with multi-infarct dementia

    International Nuclear Information System (INIS)

    Hanyu, Haruo; Imon, Yukari; Asano, Tetsuichi; Iwamoto, Toshihiko; Takasaki, Masaru

    1998-01-01

    Using magnetization transfer (MT) imaging, we studied the underlying pathological conditions of periventricular hyperintense (PVH) white matter changes seen on T2-weighted MR images of patients with multi-infarct dementia. Twenty-two patients with multiple lacunar infarcts and PVH lesions, including 11 with dementia (diagnosed as multi-infarct dementia) and 11 without dementia, and 10 control subjects (with multiple lacunes, but no PVH lesion) were studied using the MT technique. MT ratios (MTRs) were calculated for PVH lesions (normal-appearing frontal white matter in controls) and the genu of the corpus callosum. Signal intensities on T2-weighted images in PVH lesions of patients were significantly higher than those in normal-appearing white matter of controls, while there were no significant differences in signal intensity in the genu of the corpus callosum among the dementia, non-dementia and control groups. However, MTRs in patients with PVH lesions were significantly lower than those in controls, and MTRs in demented patients were significantly lower than those in non-demented patients. Moreover, MTRs in the genu of the corpus callosum of demented patients were significantly lower than in those in non-demented patients and controls. MTRs in PVH lesions and the genu of the corpus callosum significantly correlated with Hasegawa's dementia scale score. These results suggest that there is some difference in histopathologic changes of PVH lesions between demented and non-demented patients and that the pathological substrate in the corpus callosum may play a role in inducing cognitive decline. Studies with MT imaging may allow the characterization of different pathological conditions that cannot be visualized by conventional MRI. (author)

  5. Clinical significance of periventricular high intensity lesions on magnetic resonance imaging in dementia

    International Nuclear Information System (INIS)

    Kaieda, Makoto

    1991-01-01

    In this study, vascular dementia (VD, 31 cases), senile dementia of Alzheimer type (DAT, 36 cases) and mixed type dementia (14 cases) were studied by means of magnetic resonance imaging (MRI). Diagnosis of dementia was made according to DSM-III and Hachinski's ischemic score. The areas of periventricular high intensity lesions (PVH) and those of brain parenchyma were measured by digitizer which was connected to a computer. The PVH score was obtained by dividing the areas of PVH by those of brain parenchyma at the level of the body of the lateral ventricle. A multiple variable analysis was applied to the PVH scores and risk factors for dementia using Hayashi's quantification method I. The multiple correlation coefficient between the PVH and the risk factors was 0.685. The most significant correlation was found between Hachinski's ischemic score and the PVH score (partial correlation coefficient: 0.58). Significant correlations were also found between ADL and the PVH score (0.25), as well as between the Hasegawa dementia score and the PVH score (0.24). Using the student T test, it was shown that the large PVH group was significantly correlated to poor ADL, whereas the small PVH group was not. The large PVH group in VD showed lower Hasegawa score than the small PVH group. On the other hand, there was no such correlation in DAT. PVH with prolongation of T2 could exist in various pathological states irrespective of their causes. Diffuse PVH tended to be frequently observed in VD together with poor ADL. It was therefore thought that brain ischemia was the main cause of PVH. (author)

  6. Clinical significance of periventricular high intensity lesions on magnetic resonance imaging in dementia

    Energy Technology Data Exchange (ETDEWEB)

    Kaieda, Makoto [Nippon Medical School, Tokyo (Japan)

    1991-04-01

    In this study, vascular dementia (VD, 31 cases), senile dementia of Alzheimer type (DAT, 36 cases) and mixed type dementia (14 cases) were studied by means of magnetic resonance imaging (MRI). Diagnosis of dementia was made according to DSM-III and Hachinski's ischemic score. The areas of periventricular high intensity lesions (PVH) and those of brain parenchyma were measured by digitizer which was connected to a computer. The PVH score was obtained by dividing the areas of PVH by those of brain parenchyma at the level of the body of the lateral ventricle. A multiple variable analysis was applied to the PVH scores and risk factors for dementia using Hayashi's quantification method I. The multiple correlation coefficient between the PVH and the risk factors was 0.685. The most significant correlation was found between Hachinski's ischemic score and the PVH score (partial correlation coefficient: 0.58). Significant correlations were also found between ADL and the PVH score (0.25), as well as between the Hasegawa dementia score and the PVH score (0.24). Using the student T test, it was shown that the large PVH group was significantly correlated to poor ADL, whereas the small PVH group was not. The large PVH group in VD showed lower Hasegawa score than the small PVH group. On the other hand, there was no such correlation in DAT. PVH with prolongation of T2 could exist in various pathological states irrespective of their causes. Diffuse PVH tended to be frequently observed in VD together with poor ADL. It was therefore thought that brain ischemia was the main cause of PVH. (author).

  7. Stereo-EEG: Diagnostic and therapeutic tool for periventricular nodular heterotopia epilepsies.

    Science.gov (United States)

    Mirandola, Laura; Mai, Roberto F; Francione, Stefano; Pelliccia, Veronica; Gozzo, Francesca; Sartori, Ivana; Nobili, Lino; Cardinale, Francesco; Cossu, Massimo; Meletti, Stefano; Tassi, Laura

    2017-11-01

    Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug-resistant epilepsy (DRE). Stereo-electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone (EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation (SEEG-guided RF-TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG-guided RF-TC. Twenty patients with DRE related to PNHs were studied. Inclusion criteria were the following: (1) patients with epilepsy and PNHs (unilateral or bilateral, single or multiple nodules) diagnosed on brain magnetic resonance imaging (MRI); (2) SEEG recordings available as part of the presurgical investigations, with at least one intracerebral electrode inside the heterotopia; (3) complete surgical workup with SEEG-guided RF-TC and/or with traditional neurosurgery, with a follow-up of at least 12 months. Complex and heterogenic epileptic networks were found in these patients. SEEG-guided RF-TC both into the nodules and/or the cortex was efficacious in the 76% of patients. Single or multiple, unilateral or bilateral PNHs are the most suitable for this procedure, whereas patients with PNHs associated with complex cortical malformations obtained excellent outcome only with traditional resective surgery. Each patient had a specific epileptogenic network, independent from the number, size, or location of nodules and from the cortical malformation associated with. SEEG-guided RF-TC appears as a new and very effective diagnostic and therapeutic approach for DRE related to PNHs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  8. Integrity of the corpus callosum in patients with periventricular nodular heterotopia related epilepsy by FLNA mutation.

    Science.gov (United States)

    Liu, Wenyu; An, Dongmei; Niu, Running; Gong, Qiyong; Zhou, Dong

    2018-01-01

    To investigate the quantitative diffusion properties of the corpus callosum (CC) in a large group of patients with periventricular nodular heterotopia (PNH) related epilepsy and to further investigate the effect of Filamin A ( FLNA ) mutation on these properties. Patients with PNH (n = 34), subdivided into FLNA -mutated (n = 11) and FLNA -nonmutated patients (n = 23) and healthy controls (n = 34), underwent 3.0 T structural MRI and diffusion imaging scan (64 direction). Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the three major subdivisions of the CC (genu, body and splenium). Correlations between DTI metric changes and clinical parameters were also evaluated. Furthermore, the effect of FLNA mutation on structural integrity of the corpus callosum was examined. Patients with PNH and epilepsy had significant reductions in FA for the genu and splenium of the CC, accompanied by increases in MD for the splenium, as compared to healthy controls. There were no correlations between clinical parameters of epilepsy and MD. The FA value in the splenium negatively correlated with epilepsy duration. Interestingly, FLNA -mutated patients showed significantly decreased FA for all three major subdivisions of the CC, and increased MD for the genu and splenium, as compared to HCs and FLNA -nonmutated patients. These findings support the conclusion that patients with epilepsy secondary to PNH present widespread microstructural changes found in the corpus callosum that extend beyond the macroscopic MRI-visible lesions. This study also indicates that FLNA may affect white matter integrity in this disorder.

  9. Sporadic periventricular nodular heterotopia: Classification, phenotype and correlation with Filamin A mutations.

    Science.gov (United States)

    Liu, Wenyu; Yan, Bo; An, Dongmei; Xiao, Jiahe; Hu, Fayun; Zhou, Dong

    2017-07-01

    The purpose of this study was to better delineate the clinical spectrum of periventricular nodular heterotopia (PNH) in a large patient population after long term follow up. Specifically, this study aimed to relate PNH subtypes to clinical or epileptic outcomes, epileptic discharges and underlying Filamin A (FLNA) mutations by analyzing anatomical features. The study included 100 patients with radiologically confirmed nodular heterotopia. Patients' FLNA gene sequences and medical records were analyzed. Two-sided Chi-square test and Fisher's exact t-test were used to assess associations between the distribution of PNHs and specific clinical features. Based on imaging data, patients were subdivided into three groups: (a) classical (bilateral frontal and body, n=41 patients), (b) bilateral asymmetrical or posterior (n=16) and (c) unilateral heterotopia (n=43). Most patients with classical heterotopia were females (P=0.033) and were likely to have arachnoid cysts (P=0.025) and cardiac abnormalities (P=0.041), but were mostly seizure-free. Additionally, hippocampal abnormalities (P=0.022), neurological deficits (P=0.028) and cerebellar abnormalities (P=0.005) were more common in patients with bilateral asymmetrical heterotopia. Patients with unilateral heterotopia were prone to develop refractory epilepsy (P=0.041). FLNA mutations were identified in 8 patients. Each group's distinctive genetic mutations, epileptic discharge patterns and overall clinical outcomes confirm that the proposed classification system is reliable. These findings could not only be an indicator of a more severe morphological and clinical phenotype, but could also have clinical implications with respect to the epilepsy management and optimization of therapeutic options. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Diffusion-weighted MR imaging in the early diagnosis of periventricular leukomalacia

    International Nuclear Information System (INIS)

    Bozzao, Alessandro; Di Paolo, Ambrogio; Simonetti, Alessandra; Mazzoleni, Clarissa; Fasoli, Fabrizio; Floris, Roberto; Fantozzi, Luigi Maria

    2003-01-01

    Diffusion-weighted imaging (DWI) has been shown to be highly sensitive in detecting acute cerebral infarction, but its use in detecting hypoxic-ischemic encephalopathy (HIE) in neonates is still controversial. Moreover, few reports concern pre-term infants with possible periventricular leukomalacia (PVL). We examined the ability of this technique to detect cerebral changes in the acute phase of PVL. Fifteen MR examinations were performed in 11 pre-term infants (mean age 3.4 days, range 2-6 days). Conventional DWI sequences, apparent diffusion coefficient (ADC) maps, and US obtained in the acute phase were compared. All the neonates underwent US follow-up up to 4 months after delivery; those with suspected PVL also underwent MRI follow-up for up to 2 months. Qualitative and quantitative evaluations were performed to assess the presence of DW changes compatible with PVL. Diffusion-weighted MRI showed signal hyperintensity associated with decreased ADC values in 3 subjects (27%). In these patients conventional MRI sequences were interpreted as normal and US (performed at the same time) as doubtful in 2 and compatible with PVL in 1 subject. The MRI and US follow-up confirmed severe damage in all these patients. In 1 neonate hemorrhages involving the germinative matrix were identified. In 8 neonates MRI was considered normal. In these subjects US follow-up (up to 4 months) confirmed no signs of PVL. Diffusion-weighted imaging may have a higher correlation with later evidence of PVL than does conventional MR imaging and US when performed in the acute phase of the disease. (orig.)

  11. Neurodevelopmental and Behavioral Outcomes in Extremely Premature Neonates With Ventriculomegaly in the Absence of Periventricular-Intraventricular Hemorrhage.

    Science.gov (United States)

    Pappas, Athina; Adams-Chapman, Ira; Shankaran, Seetha; McDonald, Scott A; Stoll, Barbara J; Laptook, Abbot R; Carlo, Waldemar A; Van Meurs, Krisa P; Hintz, Susan R; Carlson, Martha D; Brumbaugh, Jane E; Walsh, Michele C; Wyckoff, Myra H; Das, Abhik; Higgins, Rosemary D

    2018-01-01

    Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood. To characterize the outcomes of extremely preterm neonates younger than 27 weeks' gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks' postmenstrual age. This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks' gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks' postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017. The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes. Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial

  12. Hypothalamic glucose sensing: making ends meet

    Directory of Open Access Journals (Sweden)

    Vanessa eRouth

    2014-12-01

    Full Text Available The neuroendocrine system governs essential survival and homeostatic functions. For example, growth is needed for development. Thermoregulation maintains optimal core temperature in a changing environment. Reproduction ensures species survival. Stress and immune responses enable an organism to overcome external and internal threats. The circadian system regulates arousal and sleep such that vegetative and active functions do not overlap. All of these functions require a significant portion of the body’s energy. As the integrator of the neuroendocrine system, the hypothalamus carefully assesses the energy status of the body in order to appropriately partition resources to provide for each system without compromising the others. While doing so the hypothalamus must ensure that adequate glucose levels are preserved for brain function since glucose is the primary fuel of the brain. To this end, the hypothalamus contains specialized glucose sensing neurons which are scattered throughout the nuclei controlling distinct neuroendocrine functions. We hypothesize that these neurons play a key role in enabling the hypothalamus to partition energy to meet these peripheral survival needs without endangering the brain’s glucose supply. The goal of this review is to describe the varied mechanisms underlying glucose sensing in neurons within discrete hypothalamic nuclei. We will then evaluate the way in which peripheral energy status regulates glucose sensitivity. For example, during energy deficit such as fasting specific hypothalamic glucose sensing neurons become sensitized to decreased glucose. This increases the gain of the information relay when glucose availability is a greater concern for the brain. Finally, changes in glucose sensitivity under pathological conditions (e.g., recurrent insulin-hypoglycemia, diabetes will be addressed. The overall goal of this review is to place glucose sensing neurons within the context of hypothalamic control of

  13. Hypothalamic control of energy and glucose metabolism.

    Science.gov (United States)

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  14. Potential of diffusion tensor MRI in the assessment of periventricular leukomalacia

    International Nuclear Information System (INIS)

    Fan, G.G.; Yu, B.; Quan, S.M.; Sun, B.H.; Guo, Q.Y.

    2006-01-01

    AIM: To investigate magnetic resonance (MR) diffusion tensor imaging (DTI) and fibre tractography in the assessment of altered major white matter (WM) fibre tracts in periventricular leukomalacia (PVL). MATERIALS AND METHODS: Twelve children (male:female=7:5, age range 3-10 years; mean age=6.5 years) who had suffered PVL were included in this study. Meanwhile, Twelve age-matched normal controls (male:female=6:6, age range 4-12 years; mean age=7.3 years) with normal MRI findings and no neurological abnormalities were recruited for comparison. DTI was performed with 15 different diffusion gradient directions and DTI colour maps were created from fractional anisotropy (FA) values and the three vector elements. To identify alteration of WM fibre tracts in patient of PVL quantitatively, FA values on diffusion tensor colour maps were compared between the patients and controls. Quantitative analysis was performed using the regions of interest (ROI) method settled on the central part of all identifiable WM fibres, including the corticospinal tract (CST) in the brainstem, middle cerebellar peduncle (MCP), medial lemniscus (ML), anterior/posterior limb of internal capsule (ICAL/ICPL), arcuate fasciculus (AF), posterior thalamic radiation (PTR), genu of corpus callosum (GCC), splenium of corpus callosum (SCC), corona radiata (CR), cingulum (CG), and superior longitudinal fasciculus (SLF). The averaged FA value of each WM fibre was measured and summarized as the mean±standard deviation (SD). All data were analysed by paired Student's t-test. A p-value of less than 0.05 was considered to indicate statistical significance. RESULTS: Visual investigation of WM fibre tracts showed that the ICAL, brainstem CST, ML, MCP, and external capsule (EC) was similar in controls and subjects. However, the ICPL, AF, PTR, CR, CG, SLF and corpus callosum, were all attenuated in size. All 12 cases of PVL showed a significant mean FA reduction in the ICPL, AF, PTR, CR, CG, SLF, SCC, and GCC in

  15. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

    OpenAIRE

    Merkle, Florian T.; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F.

    2015-01-01

    Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin...

  16. Radiation and the hypothalamic-pituitary axis

    International Nuclear Information System (INIS)

    Littley, M.D.; Shalet, S.M.; Beardwell, C.G.

    1991-01-01

    This paper reports on radiation therapy which is an essential treatment in the management of many conditions. It is important to appreciate the high incidence of subsequent endocrine morbidity, however, if the hypothalamic pituitary region is within the radiation fields. This is very much more common with external radiation therapy than with other forms of radiation treatment. The dose and fractional of administered radiation are important determinants of the endocrine deficits, their time on onset, and severity. Irradiation of large volumes of brain and hypothalamus may increase the risk of hormonal abnormalities as may preceding surgery in the treatment of pituitary disease. The phenomena observed in children and adults illustrate that there may be damage to pituitary, hypothalamus, and higher centers. In patients who have received a significant radiation dose to the hypothalamic-pituitary region, regular follow-up is mandatory. In adults, surveillance will include pituitary function testing on an annual basis for at least 10 years. In children careful monitoring of growth and pubertal development and early treatment of radiation-induced GH deficiency are vital

  17. Diffusion tensor MR imaging in the assessment of cognitive functions in children with periventricular leukomalacia

    International Nuclear Information System (INIS)

    Wang Shanshan; Fan Guoguang; Wang Ci; Zhou Jieqing

    2012-01-01

    Objective: To investigate the values of diffusion tensor MR imaging (DTI)and fiber tractography (FT) in the assessment of cognitive functions in children with periventricular leukomalacia (PVL), to facilitate to understand the mechanism of PVL children's cognitive functions. Methods: Forty six children with PVL and 16 age-matched volunteer were recruited. Developmental quotient (DQ) of all cases was recorded. According to the DQ scores, patients were divided into 3 groups:mild in 11 patients, moderate in 19, and severe in 16. DTI was performed in all cases and fractional anisotropy (FA) values were be calculated.Non-paired t test was used to compare the FA values of major white matter fibers between patients group and controls group. One-way ANOVA was used to compare the FA values among 4 groups. Results: Compared with controls, all 46 patients with PVL showed a significant mean FA reduction in left corticospinal tract (CST) (0.476 ±0.064 vs.0.531 ±0.064), bilateral anterior limb of internal capsula (ICAL) (left 0.357 ±0.050 vs. 0.405 ±0.081, right 0.370 ±0.040 vs. 0.405 ±0.036), posterior limb of internal capsule (ICPL) (left 0.483 ±0.044 vs. 0.546 ±0.091, right 0.485 ±0.046 vs. 0.547 ±0.083), arcuate fasciculus (AF) (left 0.367 ± 0.069 vs. 0.433 ± 0.097, right 0.363 ± 0.064 vs. 0.421 ±0.091), posterior thalamic radiation (PTR) (left 0.390 ± 0.059 vs. 0.459 ± 0.067, right 0.382 ± 0.047 vs. 0.446 ± 0.064), anterior CG (ACG) (left 0.362 ± 0.056 vs. 0.423 ± 0.057, right 0.345 ± 0.056 vs. 0.417 ± 0.080), superior longitudinal fasciculus (SLF) (left 0.323 ± 0.050 vs. 0.426 ±0.102, right 0.341 ± 0.056 vs. 0.416 ± 0.092) and splenium of the corpus callosum (SCC) (0.535 ±0.090 vs. 0.606 ±0.060) (t=2.037-3.745, P<0.05). The severity of cognitive impairment is company with decrease of the FA values of all fibers. The FA values of bilateral CST, ICAL, ICPL, left AF, bilateral PTR, ACG, SLF and SCC were significantly different among different

  18. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    Science.gov (United States)

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  19. Hypothalamic inflammation: a double-edged sword to nutritional diseases

    Science.gov (United States)

    Cai, Dongsheng; Liu, Tiewen

    2015-01-01

    The hypothalamus is one of the master regulators of various physiological processes, including energy balance and nutrient metabolism. These regulatory functions are mediated by discrete hypothalamic regions that integrate metabolic sensing with neuroendocrine and neural controls of systemic physiology. Neurons and non-neuronal cells in these hypothalamic regions act supportively to execute metabolic regulations. Under conditions of brain and hypothalamic inflammation, which may result from overnutrition-induced intracellular stresses or disease-associated systemic inflammatory factors, extracellular and intracellular environments of hypothalamic cells are disrupted, leading to central metabolic dysregulations and various diseases. Recent research has begun to elucidate the effects of hypothalamic inflammation in causing diverse components of metabolic syndrome leading to diabetes and cardiovascular disease. These new understandings have provocatively expanded previous knowledge on the cachectic roles of brain inflammatory response in diseases, such as infections and cancers. This review describes the molecular and cellular characteristics of hypothalamic inflammation in metabolic syndrome and related diseases as opposed to cachectic diseases, and also discusses concepts and potential applications of inhibiting central/hypothalamic inflammation to treat nutritional diseases. PMID:22417140

  20. Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis.

    Science.gov (United States)

    Scholly, Julia; Valenti, Maria-Paola; Staack, Anke M; Strobl, Karl; Bast, Thomas; Kehrli, Pierre; Steinhoff, Bernhard J; Hirsch, Edouard

    2013-12-01

    Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  1. Risk factors for mortality caused by hypothalamic obesity in children with hypothalamic tumours.

    Science.gov (United States)

    Haliloglu, B; Atay, Z; Guran, T; Abalı, S; Bas, S; Turan, S; Bereket, A

    2016-10-01

    Hypothalamic obesity (HyOb) is a common complication of childhood hypothalamic tumours. Patients with HyOb probably have a higher mortality rate than those with other types of obesity due in many cases to obstructive sleep apnoea/hypoventilation. To identify predictive factors for mortality caused by HyOb in children. Twenty children with HyOb secondary to hypothalamic tumours that were followed-up for ≥3 years and aged 6 years at diagnosis (3.71 ± 1.96 vs. 0.83 ± 0.73, P  1 SDS after 6 months of therapy (RR: 8.4, P obesity-related mortality rates were higher in the patients aged  0.05). The mortality rate was also 3.7-fold higher in the patients with a maximum BMI SDS ≥ 3 at any time during the first 3 years after therapy(P > 0.05). An increase in BMI SDS after 6 months of therapy was observed to be a risk factor for mortality caused by HyOb. In addition, age obesity is required. © 2015 World Obesity.

  2. Treatment of functional hypothalamic amenorrhea with hypnotherapy.

    Science.gov (United States)

    Tschugguel, Walter; Berga, Sarah L

    2003-10-01

    To determine the effects of hypnotherapy on resumption of menstruation in patients with functional hypothalamic amenorrhea (FHA). Uncontrolled clinical study. Academic clinical care center. Twelve consecutive women with FHA were selected. A single 45- to 70-minute session of hypnotherapy was administered, and patients were observed for 12 weeks. Patients were asked whether or not menstruation resumed and whether or not well-being and self-confidence changed. Within 12 weeks, 9 out of 12 patients (75%) resumed menstruation. All of the patients, including those who did not menstruate, reported several beneficial side effects such as increased general well-being and increased self-confidence. Hypnotherapy could be an efficacious and time-saving treatment option that also avoids the pitfalls of pharmacological modalities for women with FHA.

  3. Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

    Science.gov (United States)

    Berga, Sarah L; Loucks, Tammy L

    2006-12-01

    Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that

  4. Hypothalamic hamartoma associated with precocious puberty: Case report

    International Nuclear Information System (INIS)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu

    1989-01-01

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed

  5. Hypothalamic hamartoma associated with precocious puberty: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu [Soonchunhyang University, Chonan Hospital, Chonan (Korea, Republic of)

    1989-12-15

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed.

  6. Neurological evaluation of neonates with intraventricular and periventricular hemorrhage Avaliação neurológica de recém-nascidos com hemorragia intraventricular e periventricular

    Directory of Open Access Journals (Sweden)

    MONICA SANCHEZ-STOPIGLIA

    1999-06-01

    Full Text Available We studied the clinical aspects of 100 consecutive premature newborns with and without intraventricular and periventricular hemorrhage (IPVH.The diagnosis of IPVH was obtained by ultrasonic scans of the skull during the first week of life and at the age of one month. Forty eight percent of newborns with IPVH had abnormal results, and there was a significant correlation with the neurological evaluation in 85% of the infants. The probability of normality for a child with no associated brain abnormalities was 72%, whereas for a child of the same gestational age with associated brain abnormalities was 48.7%.Foram estudados os aspectos clínicos de 100 recém-nascidos prematuros, com e sem hemorragia periventricular-intraventricular (HPIV. O diagnóstico foi obtido através de exames ultra-sonográficos de crânio, realizados durante a primeira semana de vida e na idade corrigida de um mês.Quarenta e oito por cento dos recém-nascidos com HPVI evidenciaram resultados anormais, sendo a correlação significativa com a evolução neurológica, em 85% das crianças. Crianças que não apresentaram anormalidades cerebrais associadas tiveram 72% de probabilidade de manter a evolução normal, enquanto para crianças da mesma idade gestacional porém com anormalidades cerebrais associadas, a probabilidade foi 48,7%.

  7. Infantile spasms with periventricular nodular heterotopia, unbalanced chromosomal translocation 3p26.2 -10p15.1 and 6q22.31 duplication.

    Science.gov (United States)

    Jones, Kevin; Weiss, Shelly K; Minassian, Berge

    2016-07-01

    Patients presenting with infantile spasms, dysmorphic features, and periventricular nodular heterotopia may benefit from genetic copy number variation microarray, or whole-exome sequencing to identify candidate genes. This will allow personalized diagnosis and prognostication and the eventual understanding of single and combined gene functions in brain health and disease.

  8. Clinical value of periventricular low-intensity areas detected by fluid attenuated inversion recovery (FLAIR). Relationships between perinatal vital parameter and neonatal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kadowaki, Sachiko; Iwata, Osuke; Tamura, Masanori [Nagano Children' s Hospital, Toyoshina (Japan)] (and others)

    2002-01-01

    A follow-up study was performed to assess the correlation among the incidence of periventricular low intensities (PVLI) on MRI (magnetic resonance imaging) FLAIR (fluid attenuated inversion recovery) imaging, clinical evidence of perinatal insults that may cause white matter damage, and the outcome of the infants. We evaluated periventricular white matter lesions of 329 neonates whose MRI were obtained before two months corrected age. The detective rate of periventricular abnormalities on FLAIR imaging was significantly higher than that of T1-T2 weighted imaging. The most typical lesion detected on FLAIR imaging was periventricular low intensities (PVLI), frequently observed in the neonates with a history of preterm labour, very low birth weight, birth asphyxia and severe respiratory failure. Although we could not characterize the risk factors of PVLI, the incidence of PVLI had a strong correlation with the scores of motor and developmental tests at 12 and 36-months corrected age. In conclusion, FLAIR imaging, detecting the border zone damage of white matter, would be a strong tool to pick out neonates at high risk of neurological disturbances from those without clinical evidence of neurological insults in the neonatal period. (author)

  9. Association between Low-density lipoprotein cholesterol and occipital periventricular hyperintensities in a group of Chinese patients: an observational study.

    Science.gov (United States)

    Duan, Dazhi; Shen, Lin; Cui, Chun; Shu, Tongsheng; Zheng, Jian

    2017-02-27

    While occipital periventricular hyperintensities (OPVHs) are among the most common mild white matter hyperintensities, the clinical factors associated with OPVHs remain unclear. In this study, we investigated the role of clinical factors in development of pure OPVHs. This study included 97 patients with OPVHs and 73 healthy controls. Univariate analysis of clinical factors in OPVH patients and controls was followed by binomial logistic regression analysis to identify clinical factors significantly associated with OPVHs. Univariate analysis indicated that age, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (Apo-B) levels differed significantly between the OPVH patients and controls (p correlated with OPVH scores (p anti-correlated with OPVHs scores (p correlated with OPVHs (p correlated with OPVHs (p < 0.001). In summary, LDL-C was negatively and age was positively associated with OPVHs among Chinese patients in a hospital.

  10. Flash visual evoked potentials in patients with periventricular leucomalacia in children less than 1 year of age

    Directory of Open Access Journals (Sweden)

    Jitendra Jethani

    2013-01-01

    Full Text Available Background and Aim: Children with periventricular leucomalacia (PVL are known to have visual impairment of various forms starting from reduced vision, field defects, congnitive problems, and problems with hand eye coordination. There is very scant data/literature on the visual evoked potentials (VEPs at an early age in children with PVL. We did a study to evaluate the flash visual evoked potentials (fVEPs in children with PVL less than 1 year of age. Materials and Methods: A total of nine children diagnosed as having PVL on magnetic resonance imaging were included in the study. The mean age was 9.7μ 3.5 months. All children underwent handheld fVEPs under sedation at two different flash frequencies 1.4 and 8 Hz. Results: The mean latency of N1 and P1 on stimulation with 1.4 Hz was 47.9μ 15.2 and 77.7μ 26.0 ms, respectively. However, on stimulation with 8 Hz the mean latency of N1 and P1 was 189.8μ 25.6 and 238.4μ 33.6 ms, respectively. The mean amplitude with 1.4 Hz and 8 stimulation frequency was 5.6μ 4.5 and 5.59μ 3 mV, respectively. Conclusion: We have found for the first time that there is a change in the latency and the delay occurs at 8 Hz frequency but not at 1.4 Hz. We also conclude that amplitudes by fVEPs may be normal even in presence of periventricular changes. The amplitudes of fVEPs are not reliable in children with PVL.

  11. Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Andersen, M; Flyvbjerg, A

    2002-01-01

    in the central feeding mechanism in anorexia nervosa (AN). Peripheral administration of pyridostigmine (PD) minimizes the release of hypothalamic SRIH. DESIGN: To study the influence of hypothalamic somatostatinergic inhibition on the exaggerated somatotroph responsiveness to GHRH in patients with severe AN, two...... indirectly to greater SRIH withdrawal and greater GHRH release in anorexia nervosa. Moreover, hypothalamic SRIH activity seems to be inversely related to cortisol levels, indirectly supporting the hypothesis that SRIH and CRH neuronal activity are inversely related in anorexia nervosa. Leptin, which...... is believed to act on hypothalamic feeding mechanisms, seems to be positively related to SRIH activity. Finally, the present data demonstrate that the potentiating effect of pyridostigmine in anorexia nervosa is related to body mass index and increases upon weight gain, suggesting that the low...

  12. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.

    Science.gov (United States)

    Merkle, Florian T; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F

    2015-02-15

    Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases. © 2015. Published by The Company of Biologists Ltd.

  13. Delineating the regulation of energy homeostasis using hypothalamic cell models.

    Science.gov (United States)

    Wellhauser, Leigh; Gojska, Nicole M; Belsham, Denise D

    2015-01-01

    Attesting to its intimate peripheral connections, hypothalamic neurons integrate nutritional and hormonal cues to effectively manage energy homeostasis according to the overall status of the system. Extensive progress in the identification of essential transcriptional and post-translational mechanisms regulating the controlled expression and actions of hypothalamic neuropeptides has been identified through the use of animal and cell models. This review will introduce the basic techniques of hypothalamic investigation both in vivo and in vitro and will briefly highlight the key advantages and challenges of their use. Further emphasis will be place on the use of immortalized models of hypothalamic neurons for in vitro study of feeding regulation, with a particular focus on cell lines proving themselves most fruitful in deciphering fundamental basics of NPY/AgRP, Proglucagon, and POMC neuropeptide function. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Course and forecast of the hypothalamic pubertal syndrome

    International Nuclear Information System (INIS)

    Kayusheva, I.V.

    1987-01-01

    A total of 223 patients with the hypothalamic pubertal syndrome (HPS) were followed up for 1 to 22 years. The course of HPS was regressive, stable , recurrent or progressive and dependent on the initial depth and spread of hypothalamic lesion, repeated unfavourable hypothalamic exposures, and timely and regular treatment. HPS outcomes were followed up in 190 cases. The recovery was complete in 21.05%, obesity alone persisted in 10.53%, vegetovascular dystonia was persistent in 7.36%, and polycystic ovaries in 5.79%. Neuroendocrine hypothalamic syndrome was the most common (50.53%) HPS outcome. Hormone levels in blood were investigated using radioimmunoassay in patients with neuroendocrine form of HPS

  15. Leptin is an effective treatment for hypothalamic amenorrhea

    OpenAIRE

    Chou, Sharon H.; Chamberland, John P.; Liu, Xiaowen; Matarese, Giuseppe; Gao, Chuanyun; Stefanakis, Rianna; Brinkoetter, Mary T.; Gong, Huizhi; Arampatzi, Kalliopi; Mantzoros, Christos S.

    2011-01-01

    Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove d...

  16. Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating.

    Science.gov (United States)

    Warren, M P; Voussoughian, F; Geer, E B; Hyle, E P; Adberg, C L; Ramos, R H

    1999-03-01

    Because the exact etiology of functional, or idiopathic, hypothalamic amenorrhea (FHA) is still unknown, FHA remains a diagnosis of exclusion. The disorder may be stress induced. However, mounting evidence points to a metabolic/nutritional insult that may be the primary causal factor. We explored the thyroid, hormonal, dietary, behavior, and leptin changes that occur in FHA, as they provide a clue to the etiology of this disorder. Fourteen cycling control and amenorrheic nonathletic subjects were matched for age, weight, and height. The amenorrheic subjects denied eating disorders; only after further, detailed questioning did we uncover a higher incidence of anorexia and bulimia in this group. The amenorrheic subjects demonstrated scores of abnormal eating twice those found in normal subjects (P < 0.05), particularly bulimic type behavior (P < 0.01). They also expended more calories in aerobic activity per day and had higher fiber intakes (P < 0.05); lower body fat percentage (P < 0.05); and reduced levels of free T4 (P < 0.05), free T3 (P < 0.05), and total T4 (P < 0.05), without a significant change in rT3 or TSH. Cortisol averaged higher in the amenorrheics, but not significantly, whereas leptin values were significantly lower (P < 0.05). Bone mineral density was significantly lower in the wrist (P < 0.05), with a trend to lower BMD in the spine (P < 0.08). Scores of emotional distress and depression did not differ between groups. The alterations in eating patterns, leptin levels, and thyroid function present in subjects with FHA suggest altered nutritional status and the suppression of the hypothalamic-pituitary-thyroid axis or the alteration of feedback set-points in women with FHA. Both lower leptin and thyroid levels parallel changes seen with caloric restriction. Nutritional issues, particularly dysfunctional eating patterns and changes in thyroid metabolism, and/or leptin effects may also have a role in the metabolic signals suppressing GnRH secretion and

  17. Hypothalamic Circuits for Predation and Evasion.

    Science.gov (United States)

    Li, Yi; Zeng, Jiawei; Zhang, Juen; Yue, Chenyu; Zhong, Weixin; Liu, Zhixiang; Feng, Qiru; Luo, Minmin

    2018-02-21

    The interactions between predator and prey represent some of the most dramatic events in nature and constitute a matter of life and death for both sides. The hypothalamus has been implicated in driving predation and evasion; however, the exact hypothalamic neural circuits underlying these behaviors remain poorly defined. Here, we demonstrate that inhibitory and excitatory projections from the mouse lateral hypothalamus (LH) to the periaqueductal gray (PAG) in the midbrain drive, respectively, predation and evasion. LH GABA neurons were activated during predation. Optogenetically stimulating PAG-projecting LH GABA neurons drove strong predatory attack, and inhibiting these cells reversibly blocked predation. In contrast, LH glutamate neurons were activated during evasion. Stimulating PAG-projecting LH glutamate neurons drove evasion and inhibiting them impeded predictive evasion. Therefore, the seemingly opposite behaviors of predation and evasion are tightly regulated by two dissociable modular command systems within a single neural projection from the LH to the PAG. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Hypothalamic digoxin, hemispheric chemical dominance, and creativity.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-04-01

    The human hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor, digoxin, which regulates neuronal transmission. The digoxin status and neurotransmitter patterns were studied in creative and non-creative individuals, as well as in individuals with differing hemispheric dominance, in order to find out the role of cerebral dominance in this respect. The activity of HMG CoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in creative/non-creative individuals, and in individuals with differing hemispheric dominance. In creative individuals there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in creative individuals correlated with right hemispheric dominance. In non-creative individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in non-creative individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to creative tendency.

  19. Hypothalamic digoxin, hemispheric chemical dominance, and sleep.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-04-01

    The isoprenoid path way produces endogenous digoxin, a substance that can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in individuals with chronic insomnia. The patterns were compared in those with right hemispheric and left hemispheric dominance. The activity of HMG GoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in individuals with chronic insomnia and in individuals with differing hemispheric dominance. Digoxin synthesis was increased with upregulated tryptophan catabolism (increased levels of serotonin, strychnine, and nicotine), and downregulated tyrosine catabolism (decreased levels of dopamine, noradrenaline, and morphine) in those with chronic insomnia and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism (decreased levels of serotonin, strychnine, and nicotine) and upregulated tyrosine catabolism (increased levels of dopamine, noradrenaline, and morphine) in those with normal sleep patterns and left hemispheric chemical dominance. Hypothalamic digoxin plays a central role in the regulation of sleep behavior. Hemispheric chemical dominance in relation to digoxin status is also crucial.

  20. Anomalous hypothalamic responses to humor in cataplexy.

    Directory of Open Access Journals (Sweden)

    Allan L Reiss

    2008-05-01

    Full Text Available Cataplexy is observed in a subset of patients with narcolepsy and affects approximately 1 in 2,000 persons. Cataplexy is most often triggered by strong emotions such as laughter, which can result in transient, yet debilitating, muscle atonia. The objective of this study was to examine the neural systems underlying humor processing in individuals with cataplexy.While undergoing functional Magnetic Resonance Imaging (fMRI, we showed ten narcolepsy-cataplexy patients and ten healthy controls humorous cartoons. In addition, we examined the brain activity of one subject while in a full-blown cataplectic attack. Behavioral results showed that participants with cataplexy rated significantly fewer humorous cartoons as funny compared to controls. Concurrent fMRI showed that patients, when compared to controls and in the absence of overt cataplexy symptoms, showed pronounced activity in the emotional network including the ventral striatum and hypothalamus while viewing humorous versus non-humorous cartoons. Increased activity was also observed in the right inferior frontal gyri--a core component of the inhibitory circuitry. In comparison, the one subject who experienced a cataplectic attack showed dramatic reductions in hypothalamic activity.These findings suggest an overdrive of the emotional circuitry and possible compensatory suppression by cortical inhibitory regions in cataplexy. Moreover, during cataplectic attacks, the hypothalamus is characterized by a marked decrease in activity similar to that observed during sleep. One possible explanation for these findings is an initial overdrive and compensatory shutdown of the hypothalamus resulting in full cataplectic symptoms.

  1. Diagnostic and therapeutic approach to hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, Alessandro D; Ricchieri, Federica; Lanzoni, Chiara; Strucchi, Claudia; Jasonni, Valerio M

    2006-12-01

    Hypothalamic amenorrhea (HA) is a secondary amenorrhea with no evidence of endocrine/systemic causal factors, mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stress conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be exclude any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stress situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This article tries to give insights into diagnosis and putative therapeutic strategies.

  2. Psychological correlates of functional hypothalamic amenorrhea.

    Science.gov (United States)

    Marcus, M D; Loucks, T L; Berga, S L

    2001-08-01

    To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. Clinical research center in an academic medical institution. Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.

  3. Hypothalamic amenorrhea: from diagnosis to therapeutical approach.

    Science.gov (United States)

    Genazzani, A D; Chierchia, E; Santagni, S; Rattighieri, E; Farinetti, A; Lanzoni, C

    2010-05-01

    Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be excluded any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stressed situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This chapter aims to give insights into diagnosis and putative therapeutic strategies. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  4. Hypothalamic digoxin, hemispheric chemical dominance, and spirituality.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-03-01

    The isoprenoid pathway was assessed in atheistic and spiritually inclined individuals. The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has a correlation with spiritual and atheistic tendency. HMG CoA reductase activity, serum digoxin, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, and tyrosine/tryptophan catabolic patterns were assessed in spiritual/atheistic individuals and in those differing hemispheric dominance. In spiritually-inclined individuals, there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in spiritually-inclined individuals correlated with right hemispheric chemical dominance. In atheistic individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolities (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in atheistic individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to spirituality or atheism.

  5. Effects of dihydrotestosterone administration on the expression of reproductive and body weight regulatory factors in ovariectomized and estradiol-treated female rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Mayila, Yiliyasi; Irahara, Minoru

    2018-01-01

    To clarify the direct effects of androgens, the changes in the hypothalamic levels of reproductive and appetite regulatory factors induced by chronic dihydrotestosterone (DHT) administration were evaluated in female rats. DHT treatment increased the BW and food intake of the ovariectomized rats, but not the estradiol (E2)-treated rats. DHT administration suppressed the expression of a hypothalamic anorexigenic factor. Although the kisspeptin (Kiss1) mRNA levels of the anterior hypothalamic block (the anteroventral periventricular nucleus, AVPV) were increased in the E2-treated rats, DHT administration did not affect the Kiss1 mRNA levels of the AVPV in the ovariectomized or E2-treated rats. Conversely, DHT administration reduced the Kiss1 mRNA levels of the posterior hypothalamic block (the arcuate nucleus, ARC) in the ovariectomized rats. Although the Kiss1 mRNA levels of the posterior hypothalamic block (ARC) were decreased in the E2-treated rats, DHT administration did not affect the Kiss1 mRNA levels of the ARC in these rats. Serum luteinizing hormone levels of these groups exhibited similar patterns to the Kiss1 mRNA levels of the ARC. These results showed that DHT affects the production of hypothalamic reproductive and appetite regulatory factors, and that these effects of DHT differ according to the estrogen milieu.

  6. Regulation of hypothalamic NPY by diet and smoking.

    Science.gov (United States)

    Chen, Hui; Hansen, Michelle J; Jones, Jessica E; Vlahos, Ross; Bozinovski, Steve; Anderson, Gary P; Morris, Margaret J

    2007-02-01

    Appetite is regulated by a number of hypothalamic neuropeptides including neuropeptide Y (NPY), a powerful feeding stimulator that responds to feeding status, and drugs such as nicotine and cannabis. There is debate regarding the extent of the influence of obesity on hypothalamic NPY. We measured hypothalamic NPY in male Sprague-Dawley rats after short or long term exposure to cafeteria-style high fat diet (32% energy as fat) or laboratory chow (12% fat). Caloric intake and body weight were increased in the high fat diet group, and brown fat and white fat masses were significantly increased after 2 weeks. Hypothalamic NPY concentration was only significantly decreased after long term consumption of the high fat diet. Nicotine decreases food intake and body weight, with conflicting effects on hypothalamic NPY reported. Body weight, plasma hormones and brain NPY were investigated in male Balb/c mice exposed to cigarette smoke for 4 days, 4 and 12 weeks. Food intake was significantly decreased by smoke exposure (2.32+/-0.03g/24h versus 2.71+/-0.04g/24h in control mice (non-smoke exposed) at 12 weeks). Relative to control mice, smoke exposure led to greater weight loss, while pair-feeding the equivalent amount of chow caused an intermediate weight loss. Chronic smoke exposure, but not pair-feeding, was associated with decreased hypothalamic NPY concentration, suggesting an inhibitory effect of cigarette smoking on brain NPY levels. Thus, consumption of a high fat diet and smoke exposure reprogram hypothalamic NPY. Reduced NPY may contribute to the anorexic effect of smoke exposure.

  7. Surgical therapy of lesions within the hypothalamic region

    International Nuclear Information System (INIS)

    Fahlbusch, R.; Schrell, U.

    1985-01-01

    On one hand pituitary microadenomas with autonomous character and those, which had been influenced by hypothalamic disorders, are summarized and discussed. On the other hand, the neurosurgical management of tumours, adjacent to our involved with the hypothalamus, are described. Endocrinologically active pituitary adenomas are characterized by their hormone excess of ACTH, GH, and prolactin. In Cushing's disease endocrine and clinical remission occurred in 74%. 3 patients out of this group showed a reincrease of ACTH after a period of remission, indicating a possible hypothalamic influence. In acromegaly the hypothalamic influence is also discussed. One patient with an ectopic GRF-producing tumour showing a reincrease of GH levels after successful transsphenoidal adenomectomy has been described. In microprolactinomas, 7 patients out of 45 showed a reincrease of prolactin-levels after a period of normalization, we also discussed hypothalamic disorders. Tumours with suprasellar extension such as macroadenomas without endocrine activity and meningiomas are removed nowadays with minimal risk for the life of the patients. In craniopharyngiomas radical excision is accompanied by a high risk of hypothalamic defects caused by mechanical lesions and possible secondary vasospasm. Finally the excision of a hamartoma growing from the floor of the third ventricle into the interpeduncular cistern is discussed. Up to now the successful excision could be documented by endocrinological data, which give no sign of further growth of the hamartoma. (Author)

  8. Surgical therapy of lesions within the hypothalamic region

    Energy Technology Data Exchange (ETDEWEB)

    Fahlbusch, R.; Schrell, U. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.))

    1985-01-01

    On one hand pituitary microadenomas with autonomous character and those, which had been influenced by hypothalamic disorders, are summarized and discussed. On the other hand, the neurosurgical management of tumours, adjacent to or involved with the hypothalamus, are described. Endocrinologically active pituitary adenomas are characterized by their hormone excess of ACTH, GH, and prolactin. In Cushing's disease endocrine and clinical remission occurred in 74%. 3 patients out of this group showed a reincrease of ACTH after a period of remission, indicating a possible hypothalamic influence. In acromegaly the hypothalamic influence is also discussed. One patient with an ectopic GRF-producing tumour showing a reincrease of GH levels after successful transsphenoidal adenomectomy has been described. In microprolactinomas, 7 patients out of 45 showed a reincrease of prolactin-levels after a period of normalization, we also discussed hypothalamic disorders. Tumours with suprasellar extension such as macroadenomas without endocrine activity and meningiomas are removed nowadays with minimal risk for the life of the patients. In craniopharyngiomas radical excision is accompanied by a high risk of hypothalamic defects caused by mechanical lesions and possible secondary vasospasm. Finally the excision of a hamartoma growing from the floor of the third ventricle into the interpeduncular cistern is discussed. Up to now the successful excision could be documented by endocrinological data, which give no sign of further growth of the hamartoma.

  9. A novel missense mutation in the HECT domain of NEDD4L identified in a girl with periventricular nodular heterotopia, polymicrogyria and cleft palate.

    Science.gov (United States)

    Kato, Koji; Miya, Fuyuki; Hori, Ikumi; Ieda, Daisuke; Ohashi, Kei; Negishi, Yutaka; Hattori, Ayako; Okamoto, Nobuhiko; Kato, Mitsuhiro; Tsunoda, Tatsuhiko; Yamasaki, Mami; Kanemura, Yonehiro; Kosaki, Kenjiro; Saitoh, Shinji

    2017-09-01

    We identified a novel de novo heterozygous missense mutation in the NEDD4L gene (NM_015277: c.2617G>A; p.Glu873Lys) through whole-exome sequencing in a 3-year-old girl showing severe global developmental delay, infantile spasms, cleft palate, periventricular nodular heterotopia and polymicrogyria. Mutations in the HECT domain of NEDD4L have been reported in patients with a neurodevelopmental disorder along with similar brain malformations. All patients reported with NEDD4L HECT domain mutations showed periventricular nodular heterotopia, and most had seizures, cortex anomalies, cleft palate and syndactyly. The unique constellation of clinical features in patients with NEDD4L mutations might help clinically distinguish them from patients with other genetic mutations including FLNA, which is a well-known causative gene of periventricular nodular heterotopia. Although mutations in the HECT domain of NEDD4L that lead to AKT-mTOR pathway deregulation in forced expression system were reported, our western blot analysis did not show an increased level of AKT-mTOR activity in lymphoblastoid cell lines (LCLs) derived from the patient. In contrast to the forced overexpression system, AKT-mTOR pathway deregulation in LCLs derived from our patient seems to be subtle.

  10. Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention

    Directory of Open Access Journals (Sweden)

    Christian L. Roth

    2015-09-01

    Full Text Available Hypothalamic obesity (HO occurs in patients with tumors and lesions in the medial hypothalamic region. Hypothalamic dysfunction can lead to hyperinsulinemia and leptin resistance. This review is focused on HO caused by craniopharyngiomas (CP, which are the most common childhood brain tumors of nonglial origin. Despite excellent overall survival rates, CP patients have substantially reduced quality of life because of significant long-term sequelae, notably severe obesity in about 50% of patients, leading to a high rate of cardiovascular mortality. Recent studies reported that both hyperphagia and decreased energy expenditure can contribute to severe obesity in HO patients. Recognized risk factors for severe obesity include large hypothalamic tumors or lesions affecting several medial and posterior hypothalamic nuclei that impact satiety signaling pathways. Structural damage in these nuclei often lead to hyperphagia, rapid weight gain, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue. To date, most efforts to treat HO have shown disappointing long-term success rates. However, treatments based on the distinct pathophysiology of disturbed energy homeostasis related to CP may offer options for successful interventions in the future.

  11. Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar in anorexia nervosa and healthy control subjects

    Directory of Open Access Journals (Sweden)

    Anna M Van Opstal

    2015-05-01

    Full Text Available Background. Inconsistent findings about the neurobiology of Anorexia Nervosa (AN hinder the development of effective treatments for this severe mental disorder. Therefore the need arises for elucidation of neurobiological factors involved in the pathophysiology of AN. The hypothalamus plays a key role in the neurobiological processes that govern food intake and energy homeostasis, processes that are disturbed in anorexia nervosa (AN. The present study will assess the hypothalamic response to energy intake and the hypothalamic structure in patients with AN and healthy controls. Methods. 10 women aged 18-30 years diagnosed with AN and 11 healthy, lean (BMI <23 kg/m2 women in the same age range were recruited. We used functional magnetic resonance imaging (MRI to determine function of the hypothalamus in response to glucose. Structural MRI was used to determine differences in hypothalamic volume and local grey volume using manual segmentation and voxel-based morphometry.Results. No differences were found in hypothalamic volume and neuronal activity in response to a glucose load between the patients and controls. Whole brain structural analysis showed a significant decrease in grey matter volume in the cingulate cortex in the AN patients, bilaterally.Conclusions. We argue that in spite of various known changes in the hypothalamus the direct hypothalamic response to glucose intake is similar in AN patients and healthy controls.

  12. A Rare Cause of Hypothalamic Obesity, Rohhad Syndrome: 2 Cases.

    Science.gov (United States)

    Şiraz, Ülkü Gül; Okdemir, Deniz; Direk, Gül; Akın, Leyla; Hatipoğlu, Nihal; Kendırcı, Mustafa; Kurtoğlu, Selim

    2018-03-19

    Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease that is difficult to diagnosis and distinguish from genetic obesity syndromes. The underlying causes of the disease has not been fully explained. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction and autonomic alterations. There are around 80 reported patients due to lack of recognition. We present two female patient suspected of ROHHAD due to weight gain since early childhood. The presented symptoms, respiratory and circulatory dysfunction, hypothalamic hypernatremia, hypothalamo-pituitary hormonal disorders such as santral hypothyrodism, hyperprolactinemia and santral early puberty are completely matched the criteria of ROHHAD syndrome. ROHHAD syndrome should be considered in differential diagnosis since it is difficult to distinguish from causes of monogenic obesity. Early identification of the disease reduces morbidity of the syndrome and patients require regular follow-up by a multidisciplinary approach.

  13. Hypothalamic mTOR signaling regulates food intake.

    Science.gov (United States)

    Cota, Daniela; Proulx, Karine; Smith, Kathi A Blake; Kozma, Sara C; Thomas, George; Woods, Stephen C; Seeley, Randy J

    2006-05-12

    The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

  14. Bone metabolism in anorexia nervosa and hypothalamic amenorrhea.

    Science.gov (United States)

    Chou, Sharon H; Mantzoros, Christos

    2018-03-01

    Anorexia nervosa (AN) and hypothalamic amenorrhea (HA) are states of chronic energy deprivation associated with severely compromised bone health. Poor bone accrual during adolescence followed by increased bone loss results in lifelong low bone density, degraded bone architecture, and higher risk of fractures, despite recovery from AN/HA. Amenorrhea is only one of several compensatory responses to the negative energy balance. Other hypothalamic-pituitary hormones are affected and contribute to bone deficits, including activation of hypothalamic-pituitary-adrenal axis and growth hormone resistance. Adipokines, particularly leptin, provide information on fat/energy stores, and gut hormones play a role in the regulation of appetite and food intake. Alterations in all these hormones influence bone metabolism. Restricted in scope, current pharmacologic approaches to improve bone health have had overall limited success. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase

    Directory of Open Access Journals (Sweden)

    Yuanqing Gao

    2018-01-01

    Conclusions: Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism.

  16. Potential of diffusion tensor MR imaging in the assessment of cognitive impairments in children with periventricular leukomalacia born preterm

    International Nuclear Information System (INIS)

    Wang, Shanshan; Fan, Guoguang; Xu, Ke; Wang, Ci

    2013-01-01

    Purpose: To investigate MR diffusion tensor imaging (DTI) and fiber tractography (FT) in the assessment of altered major white matter fibers correlated with cognitive functions in preterm infants with periventricular leukomalacia (PVL), to explore the neural foundation for PVL children's cognitive impairments. Materials and methods: Forty six preterm infants (16 ± 4.7 months) suffered from PVL and 16 age-matched normal controls were recruited. Developmental quotient (DQ) was recorded to evaluate PVL children's cognitive functions. According to the DQ scores, patients were divided into three groups: mild, moderate and severe cognitive impairment groups. DTI scan was performed. Fractional anisotropy (FA) values of major white matter fibers were measured and their correlation with cognitive levels was evaluated. Results: Compared with the control group, the PVL group showed a significant mean FA reduction in bilateral corticospinal tract (CST), anterior/posterior limb of internal capsule (ICAL/ICPL), arcuate fasciculus (AF), corona radiate (CR), superior longitudinal fasciculus (SLF), splenium of corpus callosum (SCC) (p < 0.05) and bilateral posterior thalamic radiation (PTR) (p < 0.01). The FA values of left CST, bilateral AF, anterior cingulum (ACG), SLF, ICAL, ICPL, PTR, CR, genu of corpus callosum (GCC), SCC and middle cerebellar peduncle showed significant negative correlations with the cognitive levels. Conclusions: DTI can provide more information for understanding the pathophysiology of cognitive impairment in preterm infants with PVL

  17. Deep versus periventricular white matter lesions and cognitive function in a community sample of middle-aged participants.

    Science.gov (United States)

    Soriano-Raya, Juan José; Miralbell, Júlia; López-Cancio, Elena; Bargalló, Núria; Arenillas, Juan Francisco; Barrios, Maite; Cáceres, Cynthia; Toran, Pere; Alzamora, Maite; Dávalos, Antoni; Mataró, Maria

    2012-09-01

    The association of cerebral white matter lesions (WMLs) with cognitive status is not well understood in middle-aged individuals. Our aim was to determine the specific contribution of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) to cognitive function in a community sample of asymptomatic participants aged 50 to 65 years. One hundred stroke- and dementia-free adults completed a comprehensive neuropsychological battery and brain MRI protocol. Participants were classified according to PVH and DWMH scores (Fazekas scale). We dichotomized our sample into low grade WMLs (participants without or with mild lesions) and high grade WMLs (participants with moderate or severe lesions). Analyses were performed separately in PVH and DWMH groups. High grade DWMHs were associated with significantly lower scores in executive functioning (-0.45 standard deviations [SD]), attention (-0.42 SD), verbal fluency (-0.68 SD), visual memory (-0.52 SD), visuospatial skills (-0.79 SD), and psychomotor speed (-0.46 SD). Further analyses revealed that high grade DWMHs were also associated with a three- to fourfold increased risk of impaired scores (i.e.,<1.5 SD) in executive functioning, verbal fluency, visuospatial skills, and psychomotor speed. Our findings suggest that only DWMHs, not PVHs, are related to diminished cognitive function in middle-aged individuals. (JINS, 2012, 18, 1-12).

  18. Normal variation of focal T2 Hyperintensities in anterior parietal periventricular white matter: Another 'Terminal Zones of Myelination'

    International Nuclear Information System (INIS)

    Park, Jong Oag; Woo, Je Ho; Ki, Tae Sung; Lee, Jong Hwa; Chung, Jin Woo; Lee, Don Young

    1994-01-01

    It has been known that there are several areas of T2 hyperintensity in normal white matter of brain, such as terminal zones of myelination, ependymitis granularis, ones of posterior internal capsule, and perivascular space. The aim of our study is to demonstrate another region of T2 hyperintensities in normal pediatric age group. We have studied brain MR for 10 normal volunteers and 35 patients without having intracranial lesions in pediatric age group(3-19 years). In 5 among 45 cases, focal T2 hyperintensities were seen in the parietal periventricular white matter beneath the postcentral gyri. They were noted as poorly defined, 5-10 mm sized areas of increased signal intensities on T2-weighted axial images. They were also characterized by bilateral, posteromedially oriented, short band-like or oval areas. Interestingly, they were directly continuous with the T2 hyperintensity of posterior internal capsule. In spite of the relatively highly frequency in the pediatric population as in our study, this finding has not been reported in the asymptomatic adults. The results show that the bilateral anterior parietal hyperintense areas may be another terminal zones of delayed myelination affecting the parietopontine tract. They should be differentiated from pathologic T2 hyperintensities by their characteristic findings

  19. Potential of diffusion tensor MR imaging in the assessment of cognitive impairments in children with periventricular leukomalacia born preterm

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shanshan, E-mail: jelly_66@126.com [Department of Radiology, The First Hospital, China Medical University, #155, Nanjing North St., Heping Dist., Shenyang, Liaoning 110001 (China); Fan, Guoguang, E-mail: cjr.fanguoguang@vip.163.com [Department of Radiology, The First Hospital, China Medical University, #155, Nanjing North St., Heping Dist., Shenyang, Liaoning 110001 (China); Xu, Ke, E-mail: cjr.xuke@vip.163.com [Department of Radiology, The First Hospital, China Medical University, #155, Nanjing North St., Heping Dist., Shenyang, Liaoning 110001 (China); Wang, Ci, E-mail: xiangxuehai19850224@yahoo.cn [Department of Radiology, The First Hospital, China Medical University, #155, Nanjing North St., Heping Dist., Shenyang, Liaoning 110001 (China)

    2013-01-15

    Purpose: To investigate MR diffusion tensor imaging (DTI) and fiber tractography (FT) in the assessment of altered major white matter fibers correlated with cognitive functions in preterm infants with periventricular leukomalacia (PVL), to explore the neural foundation for PVL children's cognitive impairments. Materials and methods: Forty six preterm infants (16 ± 4.7 months) suffered from PVL and 16 age-matched normal controls were recruited. Developmental quotient (DQ) was recorded to evaluate PVL children's cognitive functions. According to the DQ scores, patients were divided into three groups: mild, moderate and severe cognitive impairment groups. DTI scan was performed. Fractional anisotropy (FA) values of major white matter fibers were measured and their correlation with cognitive levels was evaluated. Results: Compared with the control group, the PVL group showed a significant mean FA reduction in bilateral corticospinal tract (CST), anterior/posterior limb of internal capsule (ICAL/ICPL), arcuate fasciculus (AF), corona radiate (CR), superior longitudinal fasciculus (SLF), splenium of corpus callosum (SCC) (p < 0.05) and bilateral posterior thalamic radiation (PTR) (p < 0.01). The FA values of left CST, bilateral AF, anterior cingulum (ACG), SLF, ICAL, ICPL, PTR, CR, genu of corpus callosum (GCC), SCC and middle cerebellar peduncle showed significant negative correlations with the cognitive levels. Conclusions: DTI can provide more information for understanding the pathophysiology of cognitive impairment in preterm infants with PVL.

  20. Hypocretin/orexin loss changes the hypothalamic immune response.

    Science.gov (United States)

    Tanaka, Susumu; Takizawa, Nae; Honda, Yoshiko; Koike, Taro; Oe, Souichi; Toyoda, Hiromi; Kodama, Tohru; Yamada, Hisao

    2016-10-01

    Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy. Copyright © 2016 Elsevier Inc. All

  1. Hypothalamic involvement in stress-induced hypocalcemia in rats.

    Science.gov (United States)

    Aou, S; Ma, J; Hori, T

    1993-08-20

    Although hormonal regulation of blood calcium homeostasis has been intensively investigated in the peripheral organs, the involvement of the central nervous system in calcium regulation is still poorly understood. In the present study, we found that (1) bilateral lesions of the ventromedial nucleus of the hypothalamus (VMH), but not those of the paraventricular hypothalamic nucleus or the lateral hypothalamic area, eliminated immobilization (IMB)-induced hypocalcemia, and (2) electrical stimulation of the VMH decreased the blood calcium level. The results suggest that the VMH has a hypocalcemic function and plays a role in IMB-induced hypocalcemia.

  2. Distinct α subunit variations of the hypothalamic GABAA receptor triplets (αβγ are linked to hibernating state in hamsters

    Directory of Open Access Journals (Sweden)

    Alò Raffaella

    2010-09-01

    Full Text Available Abstract Background The structural arrangement of the γ-aminobutyric acid type A receptor (GABAAR is known to be crucial for the maintenance of cerebral-dependent homeostatic mechanisms during the promotion of highly adaptive neurophysiological events of the permissive hibernating rodent, i.e the Syrian golden hamster. In this study, in vitro quantitative autoradiography and in situ hybridization were assessed in major hypothalamic nuclei. Reverse Transcription Reaction-Polymerase chain reaction (RT-PCR tests were performed for specific GABAAR receptor subunit gene primers synthases of non-hibernating (NHIB and hibernating (HIB hamsters. Attempts were made to identify the type of αβγ subunit combinations operating during the switching ON/OFF of neuronal activities in some hypothalamic nuclei of hibernators. Results Both autoradiography and molecular analysis supplied distinct expression patterns of all α subunits considered as shown by a strong (p 1 ratio (over total α subunits considered in the present study in the medial preoptic area (MPOA and arcuate nucleus (Arc of NHIBs with respect to HIBs. At the same time α2 subunit levels proved to be typical of periventricular nucleus (Pe and Arc of HIB, while strong α4 expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. the suprachiasmatic nucleus (Sch; 60%. Regarding the other two subunits (β and γ, elevated β3 and γ3 mRNAs levels mostly characterized MPOA of HIBs, while prevalently elevated expression concentrations of the same subunits were also typical of Sch, even though this time during the awakening state. In the case of Arc, notably elevated levels were obtained for β3 and γ2 during hibernating conditions. Conclusion We conclude that different αβγ subunits are operating as major elements either at the onset of torpor or during induction of the arousal state in the Syrian golden hamster. The identification of a brain regional

  3. Hypothalamic obesity after treatment for craniopharyngioma: the importance of the home environment

    NARCIS (Netherlands)

    Meijneke, Ruud W. H.; Schouten-van Meeteren, Antoinette Y. N.; de Boer, Nienke Y.; van Zundert, Suzanne; van Trotsenburg, Paul A. S.; Stoelinga, Femke; van Santen, Hanneke M.

    2015-01-01

    Abstract Hypothalamic obesity after treatment for craniopharyngioma is a well-recognized, severe problem. Treatment of hypothalamic obesity is difficult and often frustrating for the patient, the parents and the professional care-giver. Because hypothalamic obesity is caused by an underlying medical

  4. JMJD3 Is Crucial for the Female AVPV RIP-Cre Neuron-Controlled Kisspeptin-Estrogen Feedback Loop and Reproductive Function.

    Science.gov (United States)

    Song, Anying; Jiang, Shujun; Wang, Qinghua; Zou, Jianghuan; Lin, Zhaoyu; Gao, Xiang

    2017-06-01

    The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. Although most studies have focused on the hierarchy from the brain to the gonad, many questions remain unresolved concerning the feedback from the gonad to the central nervous system, especially regarding the potential epigenetic modifications in hypothalamic neurons. In the present report, we generated genetically modified mice lacking histone H3 lysine 27 (H3K27) demethylase Jumonji domain-containing 3 (JMJD3) in hypothalamic rat-insulin-promoter-expressing neurons (RIP-Cre neurons). The female mutant mice displayed late-onset obesity owing to reduced locomotor activity and decreased energy expenditure. JMJD3 deficiency in RIP-Cre neurons also results in delayed pubertal onset, an irregular estrous cycle, impaired fertility, and accelerated ovarian failure in female mice owing to the dysregulation of the hypothalamic-ovarian axis. We found that JMJD3 directly regulates Kiss1 gene expression by binding to the Kiss1 promoter and triggering H3K27me3 demethylation in the anteroventral periventricular (AVPV) nucleus. Further study confirmed that the aberrations arose from impaired kisspeptin signaling in the hypothalamic AVPV nucleus and subsequent estrogen deficiency. Estrogen replacement therapy can reverse obesity in mutant mice. Moreover, we demonstrated that Jmjd3 is an estrogen target gene in the hypothalamus. These results provide direct genetic and molecular evidence that JMJD3 is a key mediator for the kisspeptin-estrogen feedback loop. Copyright © 2017 Endocrine Society.

  5. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    NARCIS (Netherlands)

    Dwarkasing, J.T.; Witkamp, R.F.; Boekschoten, M.V.; Laak, ter M.C.; Heins, M.S.; Norren, van K.

    2016-01-01

    Background: Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections

  6. Hypothalamic leptin action is mediated by histone deacetylase 5

    DEFF Research Database (Denmark)

    Kabra, Dhiraj G; Pfuhlmann, Katrin; García-Cáceres, Cristina

    2016-01-01

    Hypothalamic leptin signalling has a key role in food intake and energy-balance control and is often impaired in obese individuals. Here we identify histone deacetylase 5 (HDAC5) as a regulator of leptin signalling and organismal energy balance. Global HDAC5 KO mice have increased food intake and...

  7. Early life stress experience may blunt hypothalamic leptin signalling

    Indian Academy of Sciences (India)

    2016-12-21

    Dec 21, 2016 ... membrane-filtered purified water were available ad libi- tum. Animals were cared for according ... Care and Use of Laboratory Animals, revised 1996. All .... section was blind-counted by hand, and STAT3 auto- counted, after ..... the hypothalamic 5-HT concentration and increases plasma lep- tin in rats. Eur.

  8. Functional MRI of human hypothalamic responses following glucose ingestion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Grond, J. van der

    2005-01-01

    The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI)

  9. Hypothalamic control of energy metabolism via the autonomic nervous system

    NARCIS (Netherlands)

    Kalsbeek, A.; Bruinstroop, E.; Yi, C. X.; Klieverik, L. P.; La Fleur, S. E.; Fliers, E.

    2010-01-01

    The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the

  10. The association between pro- and anti-inflammatory cytokine polymorphisms and periventricular leukomalacia in newborns with hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Gabriel ML

    2016-05-01

    Full Text Available Marta Lúcia Gabriel,1 Fernanda Braojos Braga,1 Mariana Rodero Cardoso,1 Ana Cláudia Lopes,2 Vânia Belintani Piatto,2 Antônio Soares Souza1 1Radiology Department, 2Morphology Department, São José do Rio Preto Medical School, FAMERP, São Paulo, BrazilBackground: Periventricular leukomalacia (PVL is a frequent consequence of hypoxic-ischemic injury. Functional cytokine gene variants that result in altered production of inflammatory (tumor necrosis factor-alpha [TNF-α] and interleukin-1beta [IL-1β] or anti-inflammatory (interleukin-10 [IL-10] cytokines may modify disease processes, including PVL.Objective: The aim of this study was to evaluate if there is a relationship between the two proinflammatory polymorphisms (TNF-σ-1031T/C and IL-1 β-511C/T and the anti-inflammatory polymorphism IL-10-1082G/A and PVL risk in Brazilian newborns with and without this injury.Materials and methods: A cross-sectional case-control study performed at the Neonatal Intensive Care Unit of the Children's Hospital and Maternity of the São José do Rio Preto Medical School (FAMERP. Fifty preterm and term newborns were examined as index cases and 50 term newborns as controls, of both sexes for both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed the three polymorphisms were amplified by polymerase chain reaction-restriction fragment length polymorphism.Results: Gestational age ranged from 25 to 39 weeks, in the case group, and in the control group it ranged from 38 to 42.5 weeks (P<0.0001. Statistically significant association was found between TNF-α-1031T/C high expression genotype TC (odds ratio [OR], 2.495; 95% confidence interval [CI], 1.10–5.63; P=0.043 as well as between genotypes (TC + CC (OR, 2.471; 95% CI, 1.10–5.55; P=0.044 and risk of PVL. Statistically significant association was found between IL-1β-511C/T high expression genotypes (CT + TT (OR, 23.120; 95% CI, 1.31–409.4; P=0.003 and risk of PVL

  11. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

    Directory of Open Access Journals (Sweden)

    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

  12. Periventricular leukomalacia in preterm children: assessment of grey and white matter and cerebrospinal fluid changes by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Tzarouchi, Loukia C.; Zikou, Anastasia; Xydis, Vassilios; Kosta, Paraskevi; Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Astrakas, Loukas G. [University of Ioannina, Department of Medical Physics, Medical School, Ioannina (Greece); Andronikou, Styliani [University of Ioannina, Intensive Care Unit, Child Health Department, Medical School, Ioannina (Greece)

    2009-12-15

    Brain plasticity in patients with periventricular leukomalacia (PVL) may suggest grey matter (GM) changes. To assess the volume of 116 GM areas and total volume of GM, white matter (WM) and cerebrospinal fluid (CSF) in preterm children with PVL, using the Statistical Parametric Mapping (SPM5) and the Individual Brain Atlases Statistical Parametric Mapping (IBASPM) toolboxes. Ten preterm children (gestational age 31.7{+-}4.2 weeks, corrected age 27.8{+-}21.7 months) with PVL and 46 matched, preterm control subjects were studied using a three-dimensional T1-weighted sequence. Volumes were calculated using SPM5 and IBASPM. GM volume in frontal superior orbital, posterior cingulum and lingual gyrus, the putamen and thalamus was significantly higher in children with PVL (3.6{+-}0.6 cm{sup 3}, 2.0{+-}0.5 cm{sup 3}, 9.7{+-}1.7 cm{sup 3}, 2.5{+-}0.6 cm{sup 3}, 2.6{+-}0.9 cm{sup 3}, respectively) than in controls (3.1{+-}0.7 cm{sup 3}, 1.5{+-}0.2 cm{sup 3}, 8.2{+-}1.3 cm{sup 3}, 1.7{+-}1.4 cm{sup 3}, 1.8{+-}0.4 cm{sup 3}, respectively). White matter volume was lower (182.1{+-}40.5 cm{sup 3}) and CSF volume was higher (300.8{+-}56.2 cm{sup 3}) in children with PVL than in controls (222.9{+-}67.2 cm{sup 3}, 219.0{+-}61.8 cm{sup 3}, respectively), P<0.05. No significant difference was found in the total GM volume and the volume of neocortex. Preterm children with PVL show regional GM volume increase, possibly explained by axonal sprouting, neuronal hypertrophy and neurogenesis, which in turn may reflect brain plasticity. (orig.)

  13. Developmental outcome of the use of etamsylate for prevention of periventricular haemorrhage in a randomised controlled trial.

    Science.gov (United States)

    Schulte, J; Osborne, J; Benson, J W T; Cooke, R; Drayton, M; Murphy, J; Rennie, J; Speidel, B

    2005-01-01

    To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate (the iRNN for ethamsylate) for prevention of periventricular haemorrhage in very low birthweight infants. Double blind, single observer, prospective follow up of placebo controlled study. Six neonatal intensive care units in the United Kingdom. Neurodevelopmental outcome was assessed in health premises or children's homes. 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age. All were inborn and weighed 1500 g or less at birth. Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days. McCarthy scales of children's abilities, standardised neurological examination, full physical examination, functional assessment, seven letter Stycar vision test, and audiometry. There was no difference between the groups in neuromotor outcome (cerebral palsy) or in the general cognitive index (GCI) of the McCarthy scales (mean GCI was 93.3 for the etamsylate group (n = 133) and 89.7 for the placebo group (n = 131); p = 0.10). There were more children with GCI < 70 (9 v 19; p = 0.047) or

  14. Exploring Deep Space - Uncovering the Anatomy of Periventricular Structures to Reveal the Lateral Ventricles of the Human Brain.

    Science.gov (United States)

    Colibaba, Alexandru S; Calma, Aicee Dawn B; Webb, Alexandra L; Valter, Krisztina

    2017-10-22

    Anatomy students are typically provided with two-dimensional (2D) sections and images when studying cerebral ventricular anatomy and students find this challenging. Because the ventricles are negative spaces located deep within the brain, the only way to understand their anatomy is by appreciating their boundaries formed by related structures. Looking at a 2D representation of these spaces, in any of the cardinal planes, will not enable visualisation of all of the structures that form the boundaries of the ventricles. Thus, using 2D sections alone requires students to compute their own mental image of the 3D ventricular spaces. The aim of this study was to develop a reproducible method for dissecting the human brain to create an educational resource to enhance student understanding of the intricate relationships between the ventricles and periventricular structures. To achieve this, we created a video resource that features a step-by-step guide using a fiber dissection method to reveal the lateral and third ventricles together with the closely related limbic system and basal ganglia structures. One of the advantages of this method is that it enables delineation of the white matter tracts that are difficult to distinguish using other dissection techniques. This video is accompanied by a written protocol that provides a systematic description of the process to aid in the reproduction of the brain dissection. This package offers a valuable anatomy teaching resource for educators and students alike. By following these instructions educators can create teaching resources and students can be guided to produce their own brain dissection as a hands-on practical activity. We recommend that this video guide be incorporated into neuroanatomy teaching to enhance student understanding of the morphology and clinical relevance of the ventricles.

  15. Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.

    Science.gov (United States)

    Farquharson, Shawna; Tournier, J-Donald; Calamante, Fernando; Mandelstam, Simone; Burgess, Rosemary; Schneider, Michal E; Berkovic, Samuel F; Scheffer, Ingrid E; Jackson, Graeme D; Connelly, Alan

    2016-12-01

    Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three-dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss κ statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss κ = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole-brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. © RSNA, 2016.

  16. Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy.

    Science.gov (United States)

    Farhan, Sali M K; Nixon, Kevin C J; Everest, Michelle; Edwards, Tara N; Long, Shirley; Segal, Dmitri; Knip, Maria J; Arts, Heleen H; Chakrabarti, Rana; Wang, Jian; Robinson, John F; Lee, Donald; Mirsattari, Seyed M; Rupar, C Anthony; Siu, Victoria M; Poulter, Michael O; Hegele, Robert A; Kramer, Jamie M

    2017-11-01

    Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly. © The Author 2017. Published by Oxford University Press.

  17. A novel truncating mutation in FLNA causes periventricular nodular heterotopia, Ehlers-Danlos-like collagenopathy and macrothrombocytopenia.

    Science.gov (United States)

    Ieda, Daisuke; Hori, Ikumi; Nakamura, Yuji; Ohshita, Hironori; Negishi, Yutaka; Shinohara, Tsutomu; Hattori, Ayako; Kato, Takenori; Inukai, Sachiko; Kitamura, Katsumasa; Kawai, Tomoki; Ohara, Osamu; Kunishima, Shinji; Saitoh, Shinji

    2018-06-01

    Filamin A (FLNA) is located in Xq28, and encodes the actin binding protein, filamin A. A mutation in FLNA is the most common cause of periventricular nodular heterotopia (PVNH), but a clear phenotype-genotype correlation has not been established. Indeed, some patients with a FLNA mutation have recently been shown to additionally have Ehlers-Danlos-like collagenopathy or macrothrombocytopenia. In an attempt to establish a clearer correlation between clinical symptoms and genotype, we have investigated a phenotype that involves thrombocytopenia in a patient with a truncation of the FLNA gene. We present the case of a 4-year-old girl who, at birth, showed a ventral hernia. At 2 months of age, she was diagnosed with patent ductus arteriosus (PDA) and aortic valve regurgitation. At 11 months, she underwent ligation of the PDA. She was also diagnosed with diaphragmatic eventration by a preoperative test. At 19 months, motor developmental delay was noted, and brain MRI revealed bilateral PVNH with mega cisterna magna. Presently, there is no evidence of epilepsy, intellectual disability or motor developmental delay. She has chronic, mild thrombocytopenia, and a platelet count that transiently decreases after viral infection. Dilation of the ascending aorta is progressing gradually. Genetic testing revealed a de novo nonsense heterozygous mutation in FLNA (NM_001456.3: c.1621G > T; p.Glu541Ter). Immunofluorescence staining of a peripheral blood smear showed a lack of filamin A expression in 21.1% of her platelets. These filamin A-negative platelets were slightly larger than her normal platelets. Our data suggests immunofluorescence staining of peripheral blood smears is a convenient diagnostic approach to identify patients with a FLNA mutation, which will facilitate further investigation of the correlation between FLNA mutations and patient phenotype. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  18. Volumetric brain differences in children with periventricular T2-signal hyperintensities: a grouping by gestational age at birth.

    Science.gov (United States)

    Panigrahy, A; Barnes, P D; Robertson, R L; Back, S A; Sleeper, L A; Sayre, J W; Kinney, H C; Volpe, J J

    2001-09-01

    The purpose of this study was to compare both the volumes of the lateral ventricles and the cerebral white matter with gestational age at birth of children with periventricular white matter (PVWM) T2-signal hyperintensities on MR images. The spectrum of neuromotor abnormalities associated with these hyperintensities was also determined. We retrospectively reviewed the MR images of 70 patients who were between the ages of 1 and 5 years and whose images showed PVWM T2-signal hyperintensities. The patients were divided into premature (n = 35 children) and term (n = 35) groups depending on their gestational age at birth. Volumetric analysis was performed on four standardized axial sections using T2-weighted images. Volumes of interest were digitized on the basis of gray-scale densities of signal intensities to define the hemispheric cerebral white matter and lateral ventricles. Age-adjusted comparisons of volumetric measurements between the premature and term groups were performed using analysis of covariance. The volume of the cerebral white matter was smaller in the premature group (54 +/- 2 cm(3)) than in the term group (79 +/- 3 cm(3), p group (30 +/- 2 cm(3)) than among those in the term group (13 +/- 1 cm(3), p groups whose PVWM T2-signal hyperintensities did not correlate with any neuromotor abnormalities but were associated with seizures or developmental delays. The differences in volumetric measurements of cerebral white matter and lateral ventricles in children with PVWM T2-signal hyperintensities are related to their gestational age at birth. Several neurologic motor abnormalities are found in children with such hyperintensities.

  19. Assessment of Cortical Visual Impairment in Infants with Periventricular Leukomalacia: a Pilot Event-Related fMRI Study

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Bing; Guo, Qiyong [Shengjing Hospital of China Medical University, Shenyang (China); Fan, Guoguang [The First Hospital of China Medical University, Shenyang (China); Liu, Na [Greater China Region of Philips, Shanghai (China)

    2011-08-15

    We wanted to investigate the usefulness of event-related (ER) functional MRI (fMRI) for the assessment of cortical visual impairment in infants with periventricular leukomalacia (PVL). FMRI data were collected from 24 infants who suffered from PVL and from 12 age-matched normal controls. Slow ER fMRI was performed using a 3.0T MR scanner while visual stimuli were being presented. Data analysis was performed using Statistical Parametric Mapping software (SPM2), the SPM toolbox MarsBar was used to analyze the region of interest data, and the time to peak (TTP) of hemodynamic response functions (HRFs) was estimated for the surviving voxels. The number of activated voxels and the TTP values of HRFs were compared. Pearson correlation analysis was performed to compare visual impairment evaluated by using Teller Acuity Cards (TAC) with the number of activated voxels in the occipital lobes in all patients. In all 12 control infants, the blood oxygenation level-dependent (BOLD) signal was negative and the maximum response was located in the anterior and superior part of the calcarine fissure, and this might correspond to the anterior region of the primary visual cortex (PVC). In contrast, for the 24 cases of PVL, there were no activated pixels in the PVC in four subjects, small and weak activations in six subjects, deviated activations in seven subjects and both small and deviated activations in three subjects. The number of active voxels in the occipital lobe was significantly correlated with the TAC-evaluated visual impairment (p < 0.001). The mean TTP of the HRFs was significantly delayed in the cases of PVL as compared with that of the normal controls. Determining the characteristics of both the BOLD response and the ER fMRI activation may play an important role in the cortical visual assessment of infants with PVL.

  20. Craniopharyngioma and hypothalamic injury: latest insights into consequent eating disorders and obesity

    Science.gov (United States)

    Müller, Hermann L.

    2016-01-01

    Purpose of review Hypothalamic alterations, pathological or treatment induced, have major impact on prognosis in craniopharyngioma patients mainly because of consequent hypothalamic obesity. Recent insight in molecular genetics, treatment strategies, risk factors and outcomes associated with hypothalamic obesity provide novel therapeutic perspectives. This review includes relevant publications since 2013. Recent findings Recent findings confirm that alterations in posterior hypothalamic areas because of tumour location and/or treatment-related injuries are associated with severe hypothalamic obesity, reduced overall survival and impaired quality of life in long-term survivors of childhood-onset craniopharyngioma. However, eating disorders are observed because of hypothalamic obesity without clear disease-specific patterns. Treatment options for hypothalamic obesity are very limited. Treatment with invasive, nonreversible bariatric methods such as Roux-en-Y gastric bypass is most efficient in weight reduction, but controversial in the paediatric population because of medical, ethical, and legal considerations. Accordingly, treatment in craniopharyngioma should focus on prevention of (further) hypothalamic injury. Presurgical imaging for grading of hypothalamic involvement should be the basis for hypothalamus-sparing strategies conducted by experienced multidisciplinary teams. Summary Until a nonsurgical therapeutic option for hypothalamic obesity for paediatric patients is found, prevention of hypothalamic injury should be the preferred treatment strategy, conducted exclusively by experienced multidisciplinary teams. PMID:26574645

  1. Mapping of kisspeptin fibres in the brain of the pro-oestrus rat

    DEFF Research Database (Denmark)

    Desroziers, E; Mikkelsen, J; Simonneaux, V

    2010-01-01

    rat brain by comparing precisely the immunoreactive pattern obtained with two antibodies: one specifically directed against kisspeptin-52 (Kp-52), the longest isoform, and the other directed against kisspeptin-10 (Kp-10) whose sequence is common to all putative mature isoforms. With both antibodies......, immunoreactive cell bodies were exclusively observed in the arcuate nucleus, and immunoreactive fibres were confined to the septo-preoptico-hypothalamic continuum of the brain. Fibres were observed in the preoptic area, the diagonal band of Broca, the septohypothalamic area, the anteroventral periventricular...... terminalis were only recognised by antibody anti-Kp-10, suggesting that anti-Kp-10 may recognise a wider range of kisspeptin isoforms than anti-Kp-52 or cross-react with molecules other than kisspeptin in rat tissue. Overall, these results illustrate the variety of projection sites of kisspeptin neurones...

  2. Regional cerebral blood flow and periventricular hyperintensity in silent cerebral infarction. Comparison with multi-infarct dementia

    International Nuclear Information System (INIS)

    Koshi, Yasuhiko; Kitamura, Shin; Nagazumi, Atushi; Tsuganesawa, Toshikazu; Terashi, Akiro

    1996-01-01

    In order to investigate relationship between regional cerebral blood flow (rCBF) and the white matter lesions on MRI in silent cerebral infarction, we quantitatively measured rCBF by 123 I-IMP autoradiography method (IMP ARG method) and single photon emission tomography (SPECT) in 36 patients with silent cerebral infarction (SCI group), 22 patients with multi-infarct dementia (MID group), and 16 control subjects without periventricular hyperintensity (PVH) and lacunar infarction on MRI (CL group). Regions of interest (ROIs) on rCBF images were set in the frontal (F), temporal (T), parietal (P), occipital (O) cortex, and the cerebral white matter (W). The severity of PVH on MRI T 2 -weighted image was divided into four grades (grade 0-3). Though the frequency of hypertension was significantly higher in SCI group and MID group compared with CL group, no significant difference was seen in the mean age among these three groups. rCBF in the white matter and cerebral cortices except the occipital cortex in SCI group was significantly low compared with CL group (rCBF SCI /rCBF CL : W 0.87, F 0.87, T 0.87, P 0.88, O 0.92). rCBF in the white matter and cerebral cortices, especially in the white matter and frontal cortex, in MID group was significantly low compared with SCI group (rCBF MID /rCBF CL : W 0.69, F 0.71, T 0.74, P 0.75, O 0.81). The mean grade of PVH in MID group was significantly higher than that in SCI group (SCI 1.1 vs MID 2.5). The severity of PVH was significantly correlated with each rCBF in the white matter and cerebral cortices, especially in the white matter and frontal cortex. Our findings suggest that the quantitative measurement of rCBF by IMP ARG method is useful for the follow-up study in the patients with silent cerebral infarction as well as the evaluation of the severity of PVH on MRI. (author)

  3. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

    Science.gov (United States)

    Fuente-Martín, Esther; García-Cáceres, Cristina; Granado, Miriam; de Ceballos, María L.; Sánchez-Garrido, Miguel Ángel; Sarman, Beatrix; Liu, Zhong-Wu; Dietrich, Marcelo O.; Tena-Sempere, Manuel; Argente-Arizón, Pilar; Díaz, Francisca; Argente, Jesús; Horvath, Tamas L.; Chowen, Julie A.

    2012-01-01

    Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity. PMID:23064363

  4. Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.

    Science.gov (United States)

    Kawakami, Akio; Okada, Nobukazu; Rokkaku, Kumiko; Honda, Kazufumi; Ishibashi, Shun; Onaka, Tatsushi

    2008-09-01

    Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.

  5. Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

    Directory of Open Access Journals (Sweden)

    Antonio eZorzano

    2015-06-01

    Full Text Available Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1 cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction.

  6. Stochastic modeling of the hypothalamic pulse generator activity.

    Science.gov (United States)

    Camproux, A C; Thalabard, J C; Thomas, G

    1994-11-01

    Luteinizing hormone (LH) is released by the pituitary in discrete pulses. In the monkey, the appearance of LH pulses in the plasma is invariably associated with sharp increases (i.e, volleys) in the frequency of the hypothalamic pulse generator electrical activity, so that continuous monitoring of this activity by telemetry provides a unique means to study the temporal structure of the mechanism generating the pulses. To assess whether the times of occurrence and durations of previous volleys exert significant influence on the timing of the next volley, we used a class of periodic counting process models that specify the stochastic intensity of the process as the product of two factors: 1) a periodic baseline intensity and 2) a stochastic regression function with covariates representing the influence of the past. This approach allows the characterization of circadian modulation and memory range of the process underlying hypothalamic pulse generator activity, as illustrated by fitting the model to experimental data from two ovariectomized rhesus monkeys.

  7. Dissecting the hypothalamic pathways that underlie innate behaviors.

    Science.gov (United States)

    Zha, Xi; Xu, Xiaohong

    2015-12-01

    Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed.

  8. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  9. Stress-associated or functional hypothalamic amenorrhea in the adolescent.

    Science.gov (United States)

    Liu, James H; Bill, Arthur H

    2008-01-01

    Stress-associated amenorrhea in the adolescent is likely similar to the disorder found in young reproductive-aged adults and is termed hypothalamic amenorrhea. The key defect is an abnormality in the secretion of gonadotropin-releasing hormone. This review examines the current studies that characterize the disorder and the plausible factor(s) that may account for the disturbances in gonadotropin-releasing hormone, and identifies directions for future research in this group of disorders.

  10. Hypothalamic control of pituitary and adrenal hormones during hypothermia.

    Science.gov (United States)

    Okuda, C; Miyazaki, M; Kuriyama, K

    1986-01-01

    In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus.

  11. Effect of cancer treatment on hypothalamic-pituitary function.

    Science.gov (United States)

    Crowne, Elizabeth; Gleeson, Helena; Benghiat, Helen; Sanghera, Paul; Toogood, Andrew

    2015-07-01

    The past 30 years have seen a great improvement in survival of children and young adults treated for cancer. Cancer treatment can put patients at risk of health problems that can develop many years later, most commonly affecting the endocrine system. Patients treated with cranial radiotherapy often develop dysfunction of the hypothalamic-pituitary axis. A characteristic pattern of hormone deficiencies develops over several years. Growth hormone is disrupted most often, followed by gonadal, adrenal, and thyroid hormones, leading to abnormal growth and puberty in children, and affecting general wellbeing and fertility in adults. The severity and rate of development of hypopituitarism is determined by the dose of radiotherapy delivered to the hypothalamic-pituitary axis. Individual growth hormone deficiencies can develop after a dose as low as 10 Gy, whereas multiple hormone deficiencies are common after 60 Gy. New techniques in radiotherapy aim to reduce the effect on the hypothalamic-pituitary axis by minimising the dose received. Patients taking cytotoxic drugs do not often develop overt hypopituitarism, although the effect of radiotherapy might be enhanced. The exception is adrenal insufficiency caused by glucocorticosteroids which, although transient, can be life-threatening. New biological drugs to treat cancer can cause autoimmune hypophysitis and hypopituitarism; therefore, oncologists and endocrinologists should be vigilant and work together to optimise patient outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Effects of sugar solutions on hypothalamic appetite regulation.

    Science.gov (United States)

    Colley, Danielle L; Castonguay, Thomas W

    2015-02-01

    Several hypotheses for the causes of the obesity epidemic in the US have been proposed. One such hypothesis is that dietary intake patterns have significantly shifted to include unprecedented amounts of refined sugar. We set out to determine if different sugars might promote changes in the hypothalamic mechanisms controlling food intake by measuring several hypothalamic peptides subsequent to overnight access to dilute glucose, sucrose, high fructose corn syrup, or fructose solutions. Rats were given access to food, water and a sugar solution for 24h, after which blood and tissues were collected. Fructose access (as opposed to other sugars that were tested) resulted in a doubling of circulating triglycerides. Glucose consumption resulted in upregulation of 7 satiety-related hypothalamic peptides whereas changes in gene expression were mixed for remaining sugars. Also, following multiple verification assays, 6 satiety related peptides were verified as being affected by sugar intake. These data provide evidence that not all sugars are equally effective in affecting the control of intake. Copyright © 2014. Published by Elsevier Inc.

  13. Juvenile muscular atrophy of the distal upper extremities associated with x-linked periventricular heterotopia with features of Ehlers-Danlos syndrome.

    Science.gov (United States)

    Hommel, Alyson L; Jewett, Tamison; Mortenson, Megan; Caress, James B

    2016-10-01

    Juvenile muscular atrophy of the distal upper extremities (JMADUE) is a rare, sporadic disorder that affects adolescent males and is characterized by progressive but self-limited weakness of the distal upper extremities. The etiology is unknown, but cervical hyperflexion has been hypothesized. We report a case of an adolescent male who presented with typical JMADUE but also had joint hypermobility and multiple congenital anomalies, including periventricular heterotopias, suggesting a multisystem syndrome. Subsequent diagnostic testing confirmed a diagnosis of JMADUE, and sequencing of the filamin-A gene showed a novel, pathogenic mutation that confirmed an additional diagnosis of X-linked periventricular heterotopias with features of Ehlers-Danlos syndrome (XLPH-EDS). The concurrent diagnosis of these 2 rare conditions suggests a pathogenic connection. It is likely that the joint hypermobility from XLPH-EDS predisposed this patient to developing JMADUE. This supports the cervical hyperflexion theory of pathogenesis. This case also expands the phenotype associated with FLNA mutations. Muscle Nerve 54: 794-797, 2016. © 2016 Wiley Periodicals, Inc.

  14. Perilesional and contralateral white matter evolution and integrity in patients with periventricular nodular heterotopia and epilepsy: a longitudinal diffusion tensor imaging study.

    Science.gov (United States)

    Liu, W; Yan, B; An, D; Niu, R; Tang, Y; Tong, X; Gong, Q; Zhou, D

    2017-12-01

    This study aimed to assess the evolution of perinodular and contralateral white matter abnormalities in patients with periventricular nodular heterotopia (PNH) and epilepsy. Diffusion tensor imaging (DTI) (64 directions) and 3 T structural magnetic resonance imaging were performed in 29 PNH patients (mean age 27.3 years), and 16 patients underwent a second scan (average time between the two scans 1.1 years). Fractional anisotropy and mean diffusivity were measured within the perilesional and contralateral white matter. Longitudinal analysis showed that white matter located 10 mm from the focal nodule displayed characteristics intermediate to tissue 5 mm away, and normal-appearing white matter (NAWM) also established evolution profiles of perinodular white matter in different cortical lobes. Compared to 29 age- and sex-matched healthy controls, significant decreased fractional anisotropy and elevated mean diffusivity values were observed in regions 5 and 10 mm from nodules (P < 0.01), whilst DTI metrics of the remaining NAWM did not differ significantly from controls. Additionally, normal DTI metrics were shown in the contralateral region in patients with unilateral PNH. Periventricular nodular heterotopia is associated with microstructural abnormalities within the perilesional white matter and the extent decreases with increasing distance from the nodule. In the homologous contralateral region, white matter diffusion metrics were unchanged in unilateral PNH. These findings have clinical implications with respect to the medical and surgical interventions of PNH-related epilepsy. © 2017 EAN.

  15. Hypothalamic obesity in patients with craniopharyngioma: Profound changes of several weight regulatory circuits

    Directory of Open Access Journals (Sweden)

    Christian eRoth

    2011-10-01

    Full Text Available One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO. This drastic condition is frequently seen in patients with craniopharyngioma (CP, an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight regulating circuitries.

  16. Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons

    Directory of Open Access Journals (Sweden)

    Ammy M. Santiago

    2016-10-01

    Full Text Available Objective: Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN, a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE and -inhibited (GI neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN, glucose sensing neurons and estrogen receptor (ER distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE. Methods: Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. Results: We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. Conclusion: These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Author Video: Author Video Watch what authors say about their articles Keywords: 17β-estradiol, AMP-activated kinase, Glucose excited neurons, Glucose inhibited neurons, Ventromedial hypothalamic nucleus, Sexual dimorphism

  17. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

  18. Hypothalamic amenorrhea in young women with underlying polycystic ovary syndrome.

    Science.gov (United States)

    Sum, Melissa; Warren, Michelle P

    2009-12-01

    The purpose of this study was to compare the hormonal/clinical profiles and markers of bone health of women with hypothalamic amenorrhea (HA) to women with suspected HA and underlying polycystic ovary syndrome (PCOS). The results indicate that compared to women with HA, women with HA and underlying PCOS exhibit higher body mass index (BMI), bone mineral densities, and incidence of hyperandrogenism, that they may exhibit increased hyperandrogenism and irregular menses with weight gain, and that they remain at similar risk for osteopenia and osteoporosis.

  19. Hepatic vagotomy alters limbic and hypothalamic neuropeptide responses to insulin-dependent diabetes and voluntary lard ingestion

    NARCIS (Netherlands)

    la Fleur, Susanne E.; Manalo, Sotara L.; Roy, Monica; Houshyar, Hani; Dallman, Mary F.

    2005-01-01

    Hypothalamic anorexigenic [corticotropin-releasing factor (CRF) and proopiomelanocortin] peptides decrease and the orexigen, neuropeptide Y, increases with diabetic hyperphagia. However, when diabetic rats are allowed to eat lard (saturated fat) as well as chow, both caloric intake and hypothalamic

  20. Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Vidarsdottir, S.; Graaf, de C.; Stafleu, A.; Osch, M.J.P.; Viergever, M.A.; Pijl, H.; Grond, van der J.

    2007-01-01

    Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion. Am J Physiol Endocrinol Metab 293: E754-E758, 2007. First published June 12, 2007; doi:10.1152/ajpendo.00231.2007. - We previously showed that hypothalamic neuronal activity, as measured by the blood

  1. Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Vidarsdottir, S.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Viergever, M.A.; Pijl, H.; Grond, J. van der

    2007-01-01

    We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load,

  2. Hypophysitis, Panhypopituitarism, and Hypothalamitis in a Scottish Terrier Dog.

    Science.gov (United States)

    Polledo, L; Oliveira, M; Adamany, J; Graham, P; Baiker, K

    2017-09-01

    A 6-year old male neutered Scottish Terrier was referred with a 1 week history of progressive lethargy and anorexia. Neurological examination localized a lesion to the forebrain and hormonal testing showed panhypopituitarism. Magnetic resonance imaging (MRI) of the brain revealed a rounded, well-defined, suprasellar central mass. The mass was slightly hyperintense to the cortical grey matter on T2-weighted (T2W), hypointense on T1-weighted (T1W) images and without T2* signal void. There was a central fusiform enhancement of the mass after contrast administration which raised the suspicion of a pituitary neoplasm. Rapid deterioration of the dog prevented further clinical investigations. Histopathologic examination revealed a lymphocytic panhypophysitis of unknown origin suspected autoimmune involving the hypothalamus (hypothalamitis). This is a unique case report of a dog presenting with inflammatory hypophysitis and hypothalamitis of suspected autoimmune origin with detailed clinical, MRI, histology and immunohistochemistry findings. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  3. Hypothalamic growth hormone releasing factor deficiency following cranial irradiation

    International Nuclear Information System (INIS)

    Ahmed, S.R.; Shalet, S.M.

    1984-01-01

    The effect of synthetic human pancreatic tumour GH releasing factor (hp GRF1-44) on GH release has been studied in 10 patients with radiation-induced GH deficiency and four normal subjects. All 10 patients showed subnormal GH responses to both an ITT (median peak GH 3.2 mU/1) and to arginine stimulation (median peak GH 2.9 mU/1), although the remainder of pituitary function was intact. Following an acute intravenous bolus (100 μg) of hp GRF1-44, there was no GH response in two patients and a subnormal but definite GH response in a further four. The remaining four patients showed a significant GH response (median peak GH level 29 mU/1; range 22-57 mU/1) to hp GRF1-44, similar in magnitude and timing to that seen in th four normals. This strongly suggests that in these four subjects, the discrepancy in GH responses to hp GRF1-44, ITT and to arginine was a result of radiation-induced hypothalamic damage leading to a deficiency of endogenous GRF. The availability of synthetic hp GRF capable of stimulating GH secretion means that the distinction between hypothalamic and pituitary causes of GH deficiency will be of considerable therapeutic importance in the future. (author)

  4. Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.

    Science.gov (United States)

    Shin, Mi-Seon; Chang, Hyukki; Namkoong, Churl; Kang, Gil Myoung; Kim, Hyun-Kyong; Gil, So Young; Yu, Ji Hee; Park, Kyeong Han; Kim, Min-Seon

    2013-01-01

    Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland and hypothalamus of mammals. However, its physiological role in neuroendocrine function is largely unknown. In the present study, we investigated the effects of intracerebroventricular (ICV) administration of clusterin on plasma pituitary hormone levels in normal rats. Single ICV injection of clusterin provoked neurohormonal changes seen under acute stress condition: increased plasma adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin expression levels were upregulated following a restraint stress, suggesting an involvement of endogenous clusterin in stress-induced neurohormonal changes. In the pituitary intermediate lobe, clusterin was coexpressed with proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC expressing AtT-20 pituitary cells increased basal and corticotropin-releasing hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels. Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a CRH-dependent manner, indicating that increased clusterin under stressful conditions may augment CRH-stimulated ACTH production and release. In summary, hypothalamic and pituitary clusterin may function as a modulator of neurohormonal responses under stressful conditions. © 2013 S. Karger AG, Basel.

  5. Early effects of cranial irradiation on hypothalamic-pituitary function

    International Nuclear Information System (INIS)

    Lam, K.S.; Tse, V.K.; Wang, C.; Yeung, R.T.; Ma, J.T.; Ho, J.H.

    1987-01-01

    Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT

  6. MRI of the hypothalamic-pituitary axis in children

    International Nuclear Information System (INIS)

    Argyropoulou, Maria I.; Kiortsis, Dimitrios Nikiforos

    2005-01-01

    In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults. (orig.)

  7. MRI of the hypothalamic-pituitary axis in children

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios Nikiforos [University of Ioannina, Department of Physiology, Medical School, Ioannina (Greece)

    2005-11-01

    In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults. (orig.)

  8. Functional hypothalamic amenorrhea and its influence on women's health.

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    Meczekalski, B; Katulski, K; Czyzyk, A; Podfigurna-Stopa, A; Maciejewska-Jeske, M

    2014-11-01

    Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea. There are three types of FHA: weight loss-related, stress-related, and exercise-related amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). The final consequences are complex hormonal changes manifested by profound hypoestrogenism. Additionally, these patients present mild hypercortisolemia, low serum insulin levels, low insulin-like growth factor 1 (IGF-1) and low total triiodothyronine. The aim of this work is to review the available data concerning the effects of FHA on different aspects of women's health. Functional hypothalamic amenorrhea is related to profound impairment of reproductive functions including anovulation and infertility. Women's health in this disorder is disturbed in several aspects including the skeletal system, cardiovascular system, and mental problems. Patients manifest a decrease in bone mass density, which is related to an increase in fracture risk. Therefore, osteopenia and osteoporosis are the main long-term complications of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in the lipid profile. FHA patients present significantly higher depression and anxiety and also sexual problems compared to healthy subjects. FHA patients should be carefully diagnosed and properly managed to prevent both short- and long-term medical consequences.

  9. Leptin is an effective treatment for hypothalamic amenorrhea.

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    Chou, Sharon H; Chamberland, John P; Liu, Xiaowen; Matarese, Giuseppe; Gao, Chuanyun; Stefanakis, Rianna; Brinkoetter, Mary T; Gong, Huizhi; Arampatzi, Kalliopi; Mantzoros, Christos S

    2011-04-19

    Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.

  10. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

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    Cornelia eSchöne

    2012-11-01

    Full Text Available Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx, are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters. Indeed, most hypothalamic neurons, including hcrt/orx cells, contain fast transmitters glutamate and GABA, as well as several neuropeptides. What are the roles and relations between different transmitters expressed by the same neuron? Here, we consider signaling codes for releasing different transmitters in relation to transmitter and receptor diversity in behaviorally-defined, widely-projecting peptidergic neurons, such as hcrt/orx cells. We then discuss latest optogenetic studies of endogenous transmitter release from defined sets of axons in situ, which suggest that recently-characterized vital peptidergic neurons (e.g. hcrt/orx, proopiomelanocortin , and agouti-related peptide cells, as well as classical modulatory neurons (e.g. dopamine and acetylcholine cells, all use fast transmitters to control their postsynaptic targets. These optogenetic insights are complemented by recent observations of behavioral deficiencies caused by genetic ablation of fast transmission from specific neuropeptidergic and aminergic neurons. Powerful and fast (millisecond-scale GABAergic and glutamatergic signaling from neurons previously considered to be primarily modulatory raises new questions about the roles of slower co-transmitters they co-express.

  11. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance

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    Loh, Kim; Fukushima, Atsushi; Zhang, Xinmei; Galic, Sandra; Briggs, Dana; Enriori, Pablo J.; Simonds, Stephanie; Wiede, Florian; Reichenbach, Alexander; Hauser, Christine; Sims, Natalie A.; Bence, Kendra K.; Zhang, Sheng; Zhang, Zhong-Yin; Kahn, Barbara B.; Neel, Benjamin G.; Andrews, Zane B.; Cowley, Michael A.; Tiganis, Tony

    2011-01-01

    SUMMARY In obesity, anorectic responses to leptin are diminished, giving rise to the concept of ‘leptin resistance’. Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high fat diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity. PMID:22000926

  12. A treasure trove of hypothalamic neurocircuitries governing body weight homeostasis.

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    Vianna, Claudia R; Coppari, Roberto

    2011-01-01

    Changes in physical activities and feeding habits have transformed the historically rare disease of obesity into a modern metabolic pandemic. Obesity occurs when energy intake exceeds energy expenditure over time. This energy imbalance significantly increases the risk for cardiovascular disease and type 2 diabetes mellitus and as such represents an enormous socioeconomic burden and health threat. To combat obesity, a better understanding of the molecular mechanisms and neurocircuitries underlying normal body weight homeostasis is required. In the 1940s, pioneering lesion experiments unveiled the importance of medial and lateral hypothalamic structures. In the 1980s and 1990s, several neuropeptides and peripheral hormones critical for appropriate feeding behavior, energy expenditure, and hence body weight homeostasis were identified. In the 2000s, results from metabolic analyses of genetically engineered mice bearing mutations only in selected neuronal groups greatly advanced our knowledge of the peripheral/brain feedback-loop modalities by which central neurons control energy balance. In this review, we will summarize these recent progresses with particular emphasis on the biochemical identities of hypothalamic neurons and molecular components underlying normal appetite, energy expenditure, and body weight homeostasis. We will also parse which of those neurons and molecules are critical components of homeostatic adaptive pathways against obesity induced by hypercaloric feeding.

  13. Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

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    Federica Guaraldi

    2015-05-01

    Full Text Available Background: Traumatic brain injury (TBI is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A. The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.

  14. Glucose and hypothalamic astrocytes: More than a fueling role?

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    Leloup, C; Allard, C; Carneiro, L; Fioramonti, X; Collins, S; Pénicaud, L

    2016-05-26

    Brain plays a central role in energy homeostasis continuously integrating numerous peripheral signals such as circulating nutrients, and in particular blood glucose level, a variable that must be highly regulated. Then, the brain orchestrates adaptive responses to modulate food intake and peripheral organs activity in order to achieve the fine tuning of glycemia. More than fifty years ago, the presence of glucose-sensitive neurons was discovered in the hypothalamus, but what makes them specific and identifiable still remains disconnected from their electrophysiological signature. On the other hand, astrocytes represent the major class of macroglial cells and are now recognized to support an increasing number of neuronal functions. One of these functions consists in the regulation of energy homeostasis through neuronal fueling and nutrient sensing. Twenty years ago, we discovered that the glucose transporter GLUT2, the canonical "glucosensor" of the pancreatic beta-cell together with the glucokinase, was also present in astrocytes and participated in hypothalamic glucose sensing. Since then, many studies have identified other actors and emphasized the astroglial participation in this mechanism. Growing evidence suggest that astrocytes form a complex network and have to be considered as spatially coordinated and regulated metabolic units. In this review we aim to provide an updated view of the molecular and respective cellular pathways involved in hypothalamic glucose sensing, and their relevance in physiological and pathological states. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Sweet taste signaling functions as a hypothalamic glucose sensor

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    Xueying Ren

    2009-06-01

    Full Text Available Brain glucosensing is essential for normal body glucose homeostasis and neuronal function. However, the exact signaling mechanisms involved in the neuronal sensing of extracellular glucose levels remain poorly understood. Of particular interest is the identification of candidate membrane molecular sensors allowing neurons to change firing rates independently of intracellular glucose metabolism. Here we describe for the first time the expression of the taste receptor genes Tas1r1, Tas1r2 and Tas1r3, and their associated G-protein genes, in the mammalian brain. Neuronal expression of taste genes was detected in different nutrient-sensing forebrain regions, including the paraventricular and arcuate nuclei of the hypothalamus, the CA fields and dentate gyrus of the hippocampus, the habenula, and cortex. Expression was also observed in the intra-ventricular epithelial cells of the choroid plexus. These same regions were found to express the corresponding gene products that form the heterodimeric T1R2/T1R3 and T1R1/T1R3 sweet and L-amino acid taste G-protein coupled receptors, respectively. These regions were also found to express the taste G-protein α-Gustducin. Moreover, in vivo studies in mice demonstrate that the hypothalamic expression of taste-related genes is regulated by the nutritional state of the animal, with food deprivation significantly increasing expression levels of Tas1r1 and Tas1r2 in hypothalamus, but not in cortex. Furthermore, exposing mouse hypothalamic cells to a low-glucose medium, while maintaining normal L-amino acid concentrations, specifically resulted in higher expression levels of the sweet-associated gene Tas1r2. This latter effect was reversed by adding the non-metabolizable artificial sweetener sucralose to the low-glucose medium, indicating that taste-like signaling in hypothalamic neurons does not require intracellular glucose oxidation. Our findings suggest that the G-protein coupled sweet receptor T1R2/T1R3 is a

  16. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.

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    Zhang, Yalin; Kim, Min Soo; Jia, Baosen; Yan, Jingqi; Zuniga-Hertz, Juan Pablo; Han, Cheng; Cai, Dongsheng

    2017-08-03

    It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.

  17. Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents

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    Ja Hye Kim

    2013-12-01

    Full Text Available The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11β-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding, effective treatment for hypothalamic obesity has not yet been developed. Therefore, understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology, endocrine characteristics, and treatment strategies of hypothalamic obesity.

  18. Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

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    Ji-Ah Kang

    Full Text Available The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

  19. [Patients with functional hypothalamic amenorrhea are characterized by low serum inhibin B concentrations].

    Science.gov (United States)

    Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Meczekalski, Błazej; Petraglia, Felice

    2010-05-01

    Functional hypothalamic disturbances may be the cause of secondary amenorrhea and are related to aberration in both the pattern of pulsatility and amplitude in the release of gonadotropin-releasing hormone (GnRH) in hypothalamus. Inhibin B, as an ovarian peptide plays a crucial role in reproduction function throughout regulation of folliculotropin (FSH) pituitary production and inhibiting GnRH secretion during the menstrual cycle. To measure and estimate serum inhibin B concentration in patients with functional hypothalamic amenorrhea. Material and methods. The study included 41 women suffering from functional hypothalamic amenorrhea. Secondary amenorrhea was defined as the lack of menstruation lasting at least 90 days not due to pregnancy, characterized by low serum concentrations of lutropin (LH < 5 mIU/ml)) and typical for functional hypothalamic disturbances anamnestic investigation. The control group consists of 40 healthy women with normal menstrual cycles and Body Mass Index (BMI between 18.5- 24.9 kg/m2). Medical history, examination and laboratory analysis of LH, FSH, estradiol (E), prolactin, testosterone and inhibin B were performed (ELISA--enzyme-linked immunosorbent assay). There are statistically lower serum inhibin B, FSH, LH, estradiol and prolactin concentrations in patients with functional hypothalamic amenorrhea in comparison to healthy women. Positive correlation between serum concentration of inhibin B and estradiol concentration was found in patients with functional hypothalamic amenorrhea. Patients with functional hypothalamic amenorrhea are characterized by statistical significant decrease in serum inhibin B concentration in comparison to the control group.

  20. Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

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    Berga, S L; Loucks-Daniels, T L; Adler, L J; Chrousos, G P; Cameron, J L; Matthews, K A; Marcus, M D

    2000-04-01

    Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

  1. Hypothalamic digoxin, hemispheric dominance, and neurobiology of love and affection.

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    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-05-01

    The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neuronal transmission. The digoxin status and neurotransmitter patterns were studied in individuals with a predilection to fall in love. It was also studied in individuals with differing hemispheric dominance to find out the role of cerebral dominance in this respect. In individuals with a predilection to fall in love there was decreased digoxin synthesis, increased membrane Na+-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern correlated with that obtained in left hemispheric chemical dominance. Hemispheric dominance and hypothalamic digoxin could regulate the predisposition to fall in love.

  2. Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment

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    Robert H. Lustig

    2011-11-01

    Full Text Available Obesity is a common complication after craniopharyngioma therapy, occurring in up to 75% of survivors. Its weight gain is unlike that of normal obesity, in that it occurs even with caloric restriction, and attempts at lifestyle modification are useless to prevent or treat the obesity. The pathogenesis of this condition involves the inability to transduce afferent hormonal signals of adiposity, in effect mimicking a state of CNS starvation. Efferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis. Lifestyle intervention is essentially useless in this syndrome, termed hypothalamic obesity. Pharmacologic treatment is also difficult, consisting of adrenergics to mimic sympathetic activity, or suppression of insulin secretion with octreotide, or both. Recently, bariatric surgery (Roux-en-Y gastric bypass, laparoscopic gastric banding, truncal vagotomy have also been attempted with variable results. Early and intensive management is required to mitigate the obesity and its negative consequences.

  3. The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome.

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    Wang, Jeff G; Lobo, Rogerio A

    2008-04-01

    Polycystic ovarian morphology (PCOM) is occasionally observed in women with hypothalamic amenorrhea (HA). Although these women with HA/PCOM meet two of the Rotterdam criteria, they are excluded from the diagnosis of polycystic ovary syndrome (PCOS) by having HA. We explored the coexistence of these two disorders in women with HA/PCOM by analyzing their androgen response to gonadotropins and by following their clinical characteristics over time. Baseline and dynamic endocrine profiles during controlled ovarian hyperstimulation for women with HA/PCOM [n = 6, median (interquartile range) age 30 yr (28-31), body mass index (BMI) 19.2 kg/m(2) (18.0-19.2)] were retrospectively compared with those of women with PCOS [n = 10, age 33 (31-34), BMI 24.8 (23.2-27.6)] and normoovulatory controls [n = 20, age 33 (31-35), BMI 21.5(20.3-23.1)]. Long-term outcomes for five women with HA/PCOM were followed during their spontaneous recovery from HA. With the exception of decreased LH [0.7 (0.3-0.8) vs. 6.0 IU/liter (4.8-7.4); P = 0.003], FSH [3.9 (2.5-5.7) vs. 7.5 IU/liter (5.3-9.5); P < 0.025], and estradiol [20 (14-24) vs. 32 pg/ml (20-39); P < 0.027], baseline endocrine profiles of women with HA/PCOM did not differ significantly from those of normoovulatory controls in terms of 17alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, and total testosterone. However, controlled ovarian hyperstimulation with similar doses of gonadotropins resulted in an excess of androgen production compared with the controls [Deltaandrostenedione per dominant follicle 0.30 (0.23-0.37) vs. 0.10 ng/ml (0.05-0.18), P = 0.005; Deltatestosterone per dominant follicle 16 (7-24) vs. 6 ng/dl (2-12), P = 0.04], and these levels were comparable to those of women with PCOS. Recovery from HA/PCOM in some patients was associated with the development of oligomenorrhea and symptoms of androgen excess. Women with HA/PCOM may have inherently hyperandrogenic ovaries but

  4. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

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    Khaled Abdallah

    Full Text Available Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG, into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project. These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

  5. Thiamine Deficiency Induces Anorexia by Inhibiting Hypothalamic AMPK

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    Liu, Mei; Alimov, Alexander; Wang, Haiping; Frank, Jacqueline A.; Katz, Wendy; Xu, Mei; Ke, Zun-Ji; Luo, Jia

    2014-01-01

    Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. Thiamine deficiency (TD) can cause a number of disorders in humans, such as Beriberi and Wernicke-Korsakoff syndrome. We demonstrated here that TD caused anorexia in C57BL/6 mice. After feeding a TD diet for 16 days, the mice displayed a significant decrease in food intake and an increase in resting energy expenditure (REE), which resulted in a severe weight loss. At the 22nd day, the food intake was reduced by 69% and 74% for male and female mice, respectively in TD group. The REE increased by 9 folds in TD group. The loss of body weight (17–24%) was similar between male and female animals and mainly resulted from the reduction of fat mass (49% decrease). Re-supplementation of thiamine (benfotiamine) restored animal's appetite, leading to a total recovery of body weight. The hypothalamic AMPK is a critical regulator of food intake. TD inhibited the phosphorylation of AMPK in the arcuate nucleus (ARN) and paraventricular nucleus (PVN) of the hypothalamus without affecting its expression. TD-induced inhibition of AMPK phosphorylation was reversed once thiamine was re-supplemented. In contrast, TD increased AMPK phosphorylation in the skeletal muscle and upregulated the uncoupling protein (UCP)-1 in brown adipose tissues which was consistent with increased basal energy expenditure. Re-administration of thiamine stabilized AMPK phosphorylation in the skeletal muscle as well as energy expenditure. Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight. PMID:24607345

  6. Heightened cortisol response to exercise challenge in women with functional hypothalamic amenorrhea.

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    Sanders, Kristen M; Kawwass, Jennifer F; Loucks, Tammy; Berga, Sarah L

    2018-02-01

    Functional hypothalamic amenorrhea is characterized by anovulation caused by reduced gonadotropin-releasing hormone drive and is associated with hypercortisolemia that has been linked to heightened hypothalamic-pituitary-adrenal reactivity to common psychological and metabolic challenges. We hypothesized that women with functional hypothalamic amenorrhea would display greater cortisol responses to exercise challenge than ovulatory women with eumenorrhea. We completed a cross-sectional comparison of 9 women with functional hypothalamic amenorrhea and 11 women with eumenorrhea who were of reproductive age, who weighed 90-110% ideal body weight, who did not exercise excessively, and who had no formal psychiatric diagnosis. Subjects completed a 20-minute submaximal exercise challenge using a cycle ergometer in a research exercise laboratory. Heart rate and circulatory cortisol, glucose, and lactate were measured at 10-minute intervals before, during, and after the exercise challenge. Baseline (t= -10 minutes) cortisol, glucose, lactate, and heart rate were comparable between groups. Glucose levels rose modestly during exercise by 2.9% in women with eumenorrhea (P=.4) but declined by 10.6% in functional hypothalamic amenorrhea (P<.03). The nadir in glucose levels in functional hypothalamic amenorrhea occurred at the end of the 20-minute exercise challenge (t= +20 min). Lactate levels rose comparably in both groups (P<.01). Heart rate increased significantly with exercise in both groups (P<.01), but the increase was smaller in subjects with functional hypothalamic amenorrhea (P<.01). Cortisol levels increased during the exercise challenge in both groups (P<.01) and peaked 10 minutes after the exercise ended (t= +30 min). At peak, subjects with functional hypothalamic amenorrhea displayed higher cortisol levels (147±22 [standard error of the mean] ng/mL) than women with eumenorrhea (96±12 ng/mL; P=.05). The mean percent increase over baseline was 62% in women with

  7. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

    Science.gov (United States)

    Oyola, Mario G; Handa, Robert J

    2017-09-01

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  8. Cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus in the rat: role of the hypothalamic paraventricular nucleus.

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    Tetsuya Kawabe

    Full Text Available The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA. The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA, neuropeptide Y (NPY, or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN. Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4 receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67, NPY, and beta-endorphin. These results indicated that: 1 at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2 lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3 at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.

  9. HPG-axis hormones during puberty : A study on the association with hypothalamic and pituitary volumes

    NARCIS (Netherlands)

    Peper, Jiska S.; Brouwer, Rachel M.; van Leeuwen, Marieke; Schnack, Hugo G.; Boomsma, Dorret I.; Kahn, Rene S.; Pol, Hilleke E. Hulshoff

    Objective: During puberty, the hypothalamus-pituitary-gonadal (HPG) axis is activated, leading to increases in luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex steroids (testosterone and estradiol) levels. We aimed to study the association between hypothalamic and pituitary

  10. Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture

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    Andrea V. Rozo

    2017-07-01

    Conclusion: These observations suggest that the acute activation of GLP1R in neonates durably alters hypothalamic architecture to limit adult weight gain and adiposity, identifying GLP1R as a therapeutic target for obesity prevention.

  11. Brain Innate Immunity Regulates Hypothalamic Arcuate Neuronal Activity and Feeding Behavior

    NARCIS (Netherlands)

    Reis, Wagner L.; Yi, Chun-Xia; Gao, Yuanqing; Tschöp, Mathias H.; Stern, Javier E.

    2015-01-01

    Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake,

  12. Hypopituitarism after external irradiation. Evidence for both hypothalamic and pituitary origin

    International Nuclear Information System (INIS)

    Samaan, N.A.; Bakdash, M.M.; Caderao, J.B.; Cangir, A.; Jesse, R.H. Jr.; Ballantyne, A.J.

    1975-01-01

    Endocrine complications after radiotherapy for tumors of the head and neck are thought to be relatively rare. The availability of synthetic hypothalamic hormones for clinical investigations and the radioimmunoassay of hormones have enabled us to study function of the hypothalamic pituitary axis in 15 patients who had radiotherapy for nasopharyngeal cancer. Fourteen had evidence of endocrine deficiency. Twelve patients had evidence of hypothalamic dysfunction, 7 developed primary pituitary hormone deficiencies, and 3 developed primary hypothyroidism. These results indicate that (1) secondary hypopituitarism due to a hypothalamic lesion after radiotherapy for nasopharyngeal cancer may be more common than suspected in the past; (2) primary hypopituitarism after irradiation of extracranial tumors can occur; and (3) primary hypothyroidism may result from irradiation of regional neck nodes

  13. Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

    Science.gov (United States)

    Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

    2015-07-21

    Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake

    OpenAIRE

    Gardiner, JV; Bataveljic, A; Patel, NA; Bewick, GA; Roy, D; Campbell, D; Greenwood, HC; Murphy, KG; Hameed, S; Jethwa, PH; Ebling, FJP; Vickers, SP; Cheetham, S; Ghatei, MA; Bloom, SR

    2009-01-01

    OBJECTIVE Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanis...

  15. Radioimmunoassay in assessment of function of the hypothalamo-neurohypophyseal system in patients with hypothalamic syndromes

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Markov, V.V.; Rudichenko, V.M.

    1991-01-01

    Radioimmunoassay of vasopressin was conducted before and after drug tests and exercise for assessment of function of the hypothalamo-neurohypophyseal system in 165 patients with hypothalamic syndromes. It was shown that radioimmunoassay gave the adequate information for assessment of function of hypothalamo-neurohypophyseal system on the base of study of basal and stimulated vasopressin secretion. It permits to make an individual choice of the most effective drug for therapy of the hypothalamic syndrome of neuroendocrine-metabolic type

  16. Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences.

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    Sei Higuchi

    Full Text Available In this study, we examined alterations in the hypothalamic reward system related to high-fat diet (HFD preferences. We previously reported that hypothalamic 2-arachidonoylglycerol (2-AG and glial fibrillary acid protein (GFAP were increased after conditioning to the rewarding properties of a HFD. Here, we hypothesized that increased 2-AG influences the hypothalamic reward system.The conditioned place preference test (CPP test was used to evaluate HFD preferences. Hypothalamic 2-AG was quantified by gas chromatography-mass spectrometry. The expression of GFAP was examined by immunostaining and western blotting.Consumption of a HFD over either 3 or 7 days increased HFD preferences and transiently increased hypothalamic 2-AG levels. HFD consumption over 14 days similarly increased HFD preferences but elicited a long-lasting increase in hypothalamic 2-AG and GFAP levels. The cannabinoid 1 receptor antagonist O-2050 reduced preferences for HFDs after 3, 7, or 14 days of HFD consumption and reduced expression of GFAP after 14 days of HFD consumption. The astrocyte metabolic inhibitor Fluorocitrate blocked HFD preferences after 14 days of HFD consumption.High levels of 2-AG appear to induce HFD preferences, and activate hypothalamic astrocytes via the cannabinoid system. We propose that there may be two distinct stages in the development of HFD preferences. The induction stage involves a transient increase in 2-AG, whereas the maintenance stage involves a long lasting increase in 2-AG levels and activation of astrocytes. Accordingly, hypothalamic 2-AG may influence the development of HFD preferences.

  17. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance

    OpenAIRE

    Kaushik, Susmita; Rodriguez-Navarro, Jose Antonio; Arias, Esperanza; Kiffin, Roberta; Sahu, Srabani; Schwartz, Gary J.; Cuervo, Ana Maria; Singh, Rajat

    2011-01-01

    Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here, we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the...

  18. Proliferative hypothalamic neurospheres express NPY, AGRP, POMC, CART and Orexin-A and differentiate to functional neurons.

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    Lígia Sousa-Ferreira

    Full Text Available Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents. The aim of the present work was to evaluate the expression of feeding-related neuropeptides in hypothalamic progenitor cells and their capacity to differentiate to functional neurons which have been described to be affected by hypothalamic dysfunction. Our study shows that hypothalamic progenitor cells from rat embryos grow as floating neurospheres and express the feeding-related neuropeptides Neuropeptide Y (NPY, Agouti-related Protein (AGRP, Pro-OpioMelanocortin (POMC, Cocaine-and-Amphetamine Responsive Transcript (CART and Orexin-A/Hypocretin-1. Moreover the relative mRNA expression of NPY and POMC increases during the expansion of hypothalamic neurospheres in proliferative conditions.Mature neurons were obtained from the differentiation of hypothalamic progenitor cells including NPY, AGRP, POMC, CART and Orexin-A positive neurons. Furthermore the relative mRNA expression of NPY, CART and Orexin-A increases after the differentiation of hypothalamic neurospheres. Similarly to the adult hypothalamic neurons the neurospheres-derived neurons express the glutamate transporter EAAT3. The orexigenic and anorexigenic phenotype of these neurons was identified by functional response to ghrelin and leptin hormones, respectively. This work demonstrates the presence of appetite-related neuropeptides in hypothalamic progenitor cells and neurons obtained from the differentiation of hypothalamic neurospheres, including the neuronal phenotypes that have been described by others as being affected by hypothalamic neurodegeneration. These in vitro models can be used to study hypothalamic progenitor cells aiming a therapeutic intervention to

  19. Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability.

    Science.gov (United States)

    Hamada, Nanako; Negishi, Yutaka; Mizuno, Makoto; Miya, Fuyuki; Hattori, Ayako; Okamoto, Nobuhiko; Kato, Mitsuhiro; Tsunoda, Tatsuhiko; Yamasaki, Mami; Kanemura, Yonehiro; Kosaki, Kenjiro; Tabata, Hidenori; Saitoh, Shinji; Nagata, Koh-Ichi

    2017-01-01

    We analyzed the role of a heterotrimeric G-protein, Gi2, in the development of the cerebral cortex. Acute knockdown of the α-subunit (Gαi2) with in utero electroporation caused delayed radial migration of excitatory neurons during corticogenesis, perhaps because of impaired morphology. The migration phenotype was rescued by an RNAi-resistant version of Gαi2. On the other hand, silencing of Gαi2 did not affect axon elongation, dendritic arbor formation or neurogenesis at ventricular zone in vivo. When behavior analyses were conducted with acute Gαi2-knockdown mice, they showed defects in social interaction, novelty recognition and active avoidance learning as well as increased anxiety. Subsequently, using whole-exome sequencing analysis, we identified a de novo heterozygous missense mutation (c.680C>T; p.Ala227Val) in the GNAI2 gene encoding Gαi2 in an individual with periventricular nodular heterotopia and intellectual disability. Collectively, the phenotypes in the knockdown experiments suggest a role of Gαi2 in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders. © 2016 International Society for Neurochemistry.

  20. Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia.

    Science.gov (United States)

    Broix, Loïc; Jagline, Hélène; Ivanova, Ekaterina; Schmucker, Stéphane; Drouot, Nathalie; Clayton-Smith, Jill; Pagnamenta, Alistair T; Metcalfe, Kay A; Isidor, Bertrand; Louvier, Ulrike Walther; Poduri, Annapurna; Taylor, Jenny C; Tilly, Peggy; Poirier, Karine; Saillour, Yoann; Lebrun, Nicolas; Stemmelen, Tristan; Rudolf, Gabrielle; Muraca, Giuseppe; Saintpierre, Benjamin; Elmorjani, Adrienne; Moïse, Martin; Weirauch, Nathalie Bednarek; Guerrini, Renzo; Boland, Anne; Olaso, Robert; Masson, Cecile; Tripathy, Ratna; Keays, David; Beldjord, Cherif; Nguyen, Laurent; Godin, Juliette; Kini, Usha; Nischké, Patrick; Deleuze, Jean-François; Bahi-Buisson, Nadia; Sumara, Izabela; Hinckelmann, Maria-Victoria; Chelly, Jamel

    2016-11-01

    Neurodevelopmental disorders with periventricular nodular heterotopia (PNH) are etiologically heterogeneous, and their genetic causes remain in many cases unknown. Here we show that missense mutations in NEDD4L mapping to the HECT domain of the encoded E3 ubiquitin ligase lead to PNH associated with toe syndactyly, cleft palate and neurodevelopmental delay. Cellular and expression data showed sensitivity of PNH-associated mutants to proteasome degradation. Moreover, an in utero electroporation approach showed that PNH-related mutants and excess wild-type NEDD4L affect neurogenesis, neuronal positioning and terminal translocation. Further investigations, including rapamycin-based experiments, found differential deregulation of pathways involved. Excess wild-type NEDD4L leads to disruption of Dab1 and mTORC1 pathways, while PNH-related mutations are associated with deregulation of mTORC1 and AKT activities. Altogether, these data provide insights into the critical role of NEDD4L in the regulation of mTOR pathways and their contributions in cortical development.

  1. Region-specific connectivity in patients with periventricular nodular heterotopia and epilepsy: A study combining diffusion tensor imaging and functional MRI.

    Science.gov (United States)

    Liu, Wenyu; An, Dongmei; Tong, Xin; Niu, Running; Gong, Qiyong; Zhou, Dong

    2017-10-01

    Periventricular nodular heterotopia (PNH) is an important cause of chronic epilepsy. The purpose of this study was to evaluate region-specific connectivity in PNH patients with epilepsy and assess correlation between connectivity strength and clinical factors including duration and prognosis. Diffusion tensor imaging (DTI) and resting state functional MRI (fMRI) were performed in 28 subjects (mean age 27.4years; range 9-56years). The structural connectivity of fiber bundles passing through the manually-selected segmented nodules and other brain regions were analyzed by tractography. Cortical lobes showing functional correlations to nodules were also determined. For all heterotopic gray matter nodules, including at least one in each subject, the most frequent segments to which nodular heterotopia showed structural (132/151) and functional (146/151) connectivity were discrete regions of the ipsilateral overlying cortex. Agreement between diffusion tensor tractography and functional connectivity analyses was conserved in 81% of all nodules (122/151). In patients with longer duration or refractory epilepsy, the connectivity was significantly stronger, particularly to the frontal and temporal lobes (P<0.05). Nodules in PNH were structurally and functionally connected to the cortex. The extent is stronger in patients with longstanding or intractable epilepsy. These findings suggest the region-specific interactions may help better evaluate prognosis and seek medical or surgical interventions of PNH-related epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. A Dual Phenotype of Periventricular Nodular Heterotopia and Frontometaphyseal Dysplasia in One Patient Caused by a Single FLNA Mutation Leading to Two Functionally Different Aberrant Transcripts

    Science.gov (United States)

    Zenker, Martin; Rauch, Anita; Winterpacht, Andreas; Tagariello, Andreas; Kraus, Cornelia; Rupprecht, Thomas; Sticht, Heinrich; Reis, André

    2004-01-01

    Two disorders, periventricular nodular heterotopia (PVNH) and a group of skeletal dysplasias belonging to the oto-palato-digital (OPD) spectrum, are caused by FLNA mutations. They are considered mutually exclusive because of the different presumed effects of the respective FLNA gene mutations, leading to loss of function (PVNH) and gain of function (OPD), respectively. We describe here the first patient manifesting PVNH in combination with frontometaphyseal dysplasia, a skeletal dysplasia of the OPD-spectrum. A novel de novo mutation, 7315C→A in exon 45 of the FLNA gene, was identified. It leads to two aberrant transcripts, one full-length transcript with the point mutation causing a substitution of a highly conserved leucine residue (L2439M) and a second shortened transcript lacking 21 bp due to the creation of an ectopic splice donor site in exon 45. We propose that the dual phenotype is caused by two functionally different, aberrant filamin A proteins and therefore represents an exceptional model case of allelic gain-of-function and loss-of-function phenotypes due to a single mutational event. PMID:14988809

  3. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation.

    Directory of Open Access Journals (Sweden)

    Hai Zhang

    2011-07-01

    Full Text Available Hypoxia-inducible factor (HIF is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.

  4. Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice

    Science.gov (United States)

    Foglesong, Grant D.; Huang, Wei; Liu, Xianglan; Slater, Andrew M.; Siu, Jason; Yildiz, Vedat; Salton, Stephen R. J.

    2016-01-01

    Environmental enrichment (EE), a housing condition providing complex physical, social, and cognitive stimulation, leads to improved metabolic health and resistance to diet-induced obesity and cancer. One underlying mechanism is the activation of the hypothalamic-sympathoneural-adipocyte axis with hypothalamic brain-derived neurotrophic factor (BDNF) as the key mediator. VGF, a peptide precursor particularly abundant in the hypothalamus, was up-regulated by EE. Overexpressing BDNF or acute injection of BDNF protein to the hypothalamus up-regulated VGF, whereas suppressing BDNF signaling down-regulated VGF expression. Moreover, hypothalamic VGF expression was regulated by leptin, melanocortin receptor agonist, and food deprivation mostly paralleled to BDNF expression. Recombinant adeno-associated virus-mediated gene transfer of Cre recombinase to floxed VGF mice specifically decreased VGF expression in the hypothalamus. In contrast to the lean and hypermetabolic phenotype of homozygous germline VGF knockout mice, specific knockdown of hypothalamic VGF in male adult mice led to increased adiposity, decreased core body temperature, reduced energy expenditure, and impaired glucose tolerance, as well as disturbance of molecular features of brown and white adipose tissues without effects on food intake. However, VGF knockdown failed to block the EE-induced BDNF up-regulation or decrease of adiposity indicating a minor role of VGF in the hypothalamic-sympathoneural-adipocyte axis. Taken together, our results suggest hypothalamic VGF responds to environmental demands and plays an important role in energy balance and glycemic control likely acting in the melanocortin pathway downstream of BDNF. PMID:26730934

  5. Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation

    Science.gov (United States)

    Zhang, Hai; Zhang, Guo; Gonzalez, Frank J.; Park, Sung-min; Cai, Dongsheng

    2011-01-01

    Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance. PMID:21814490

  6. Gelastic seizures associated with hypothalamic hamartomas. An update in the clinical presentation, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    José F. Tellez-Zenteno

    2008-10-01

    Full Text Available José F. Tellez-Zenteno1, Cesar Serrano-Almeida2, Farzad Moien-Afshari11Division of Neurology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, CanadaAbstract: Gelastic seizures are epileptic events characterized by bouts of laughter. Laughter-like vocalization is usually combined with facial contraction in the form of a smile. Autonomic features such as flushing, tachycardia, and altered respiration are widely recognized. Conscious state may not be impaired, although this is often difficult to asses particularly in young children. Gelastic seizures have been associated classically to hypothalamic hamartomas, although different extrahypothalamic localizations have been described. Hypothalamic hamartomas are rare congenital lesions presenting with the classic triad of gelastic epilepsy, precocious puberty and developmental delay. The clinical course of patients with gelastic seizures associated with hypothalamic hamartomas is progressive, commencing with gelastic seizures in infancy, deteriorating into more complex seizure disorder resulting in intractable epilepsy. Electrophysiological, radiological, and pathophysiological studies have confirmed the intrinsic epileptogenicity of the hypothalamic hamartoma. Currently the most effective surgical approach is the trancallosal anterior interforniceal approach, however newer approaches including the endoscopic and other treatment such as radiosurgery and gamma knife have been used with success. This review focuses on the syndrome of gelastic seizures associated with hypothalamic hamartomas, but it also reviews other concepts such as status gelasticus and some aspects of gelastic seizures in other locations.Keywords: epilepsy, gelastic seizures, epilepsy surgery, hypothalamic hamartoma, intractable epilepsy

  7. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

    Directory of Open Access Journals (Sweden)

    Joseph W McFadden

    Full Text Available Modification of hypothalamic fatty acid (FA metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1 and fatty acid oxidation (FAOx, exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS, and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.

  8. Hypothalamic hamartoma with precocious puberty: a case report.

    Science.gov (United States)

    Amin, M S; Kader, M A; Huq, F I; Khan, N A

    2012-07-01

    Hypothalamic hamartoma (HH) is one of the most important causes of central precocious puberty in male children. Hamartomas are malformations composed of ectopic gonadotropic hormone (GnRH) neurons which secrete pulsatile gonadotropin releasing hormone. They are generally observed in children under 3 years. A case of 11/3 year-old male child presented with premature development of secondary sexual characters i.e., growth of pubic and axillary hair, enlargement of penis and acne over the face for the last 5 months. On physical examination, his height was 1.02 m and his weight 18kg, enlarged penile length of which 58mm; testicles were enlarged in size right one measuring 32X25mm and the left 30X23mm. His hematological and other biochemical investigations revealed no abnormality. Plain radiographic examination revealed radiological bone age of about 8-9 years. Endocrinological findings were as follows: Follicle stimulating hormone (FSH): 1.5mIU/ml, Luteinizing hormone (LH): 9.1mIU/ml, Testosterone: 701ng/dl (Testosterone level less than 30ng/dl in prepubertal age). Thyroid function tests were normal. Patient showed no adrenal pathology on ultrasound and his testicular parenchyma was homogeneous echotexture with the size of 30X22X16mm on the right (volume 5.4ml) and 30X20X15mm on the left (volume 4.6ml). With above physical & endocrinological findings and age of the child, it was suspected as a case of central precocious puberty. Subsequently MR imaging of the brain done & showed an oval non-enhancing pedunculated hypothalamic mass arising from the tubercinereum that was iso to hypointense to brain parenchyma on T1 - and intermediate signal on T2-weighted images, 20X10X10mm in diameter, extending into suprasellar cistern. During follow up after 06 months of starting conservative medication with gonadotropin-releasing hormone (GnRH) analog (Leuprolide acetate), his progression of puberty has been arrested and the testosterone level 18ng/dl, which is normal for his age.

  9. Reproductive performance of male mice after hypothalamic ghrelin administration.

    Science.gov (United States)

    Poretti, Maria Belen; Frautschi, Camila; Luque, Eugenia Mercedes; Bianconi, Santiago; Martini, Ana Carolina; Stutz, Graciela; Vincenti, Laura Maria; Santillán, María Emilia; Ponzio, Marina Flavia; Schiöth, Helgi; Fiol De Cuneo, Marta Haydee; Carlini, Valeria Paola

    2018-05-23

    It has been demonstrated that food intake and reproductive physiology are both simultaneously modulated to optimize reproductive success under fluctuating metabolic conditions. Ghrelin (Ghr) is an orexigenic peptide identified as the endogenous ligand of the growth hormone secretagogue receptor that is being investigated for its potential role on reproduction. Considering that data available so far are still limited and characterization of Ghr action mechanism on the reproductive system has not been fully elucidated, we studied the hypothalamus participation in Ghr effects on sperm functional activity, plasma levels of gonodotropins and histological morphology in mice testes after hypothalamic infusion of 0.3 or 3.0 nmol/day Ghr or artificial cerebrospinal fluid (ACSF) at different treatment periods. We found that Ghr 3.0 nmol/day administration for 42 days significantly reduced sperm concentration (Ghr 3.0 nmol/day=14.05±2.44 x106/ml vs. ACSF=20.33±1.35 x106/ml, p< 0.05) and motility (Ghr 3.0 nmol/day=59.40±4.20% vs. ACSF=75.80±1.40%, p< 0.05). In addition, histological studies showed a significant decrease percentage of spermatogonia (Ghr 3.0 nmol/day=6,76±0,68% vs. ACSF=9,56±0,41%, p< 0.05) and sperm (Ghr 3.0 nmol/day=24,24±1,92% vs. ACSF=31,20±3,06%, p< 0.05). These results were associated with a significant reduction in luteinizing hormone and testosterone plasma levels (p<0.05). As Ghr is an orexigenic peptide, body weight and food intake were measured. Results showed that Ghr increases both parameters; however, the effect did not last beyond the first week of treatment. Results presented in this work confirm that central Ghr administration impairs spermatogenesis and suggest that this effect is mediated by inhibition of hypothalamic-pituitary-gonadal axis.

  10. Amino acid sensing in hypothalamic tanycytes via umami taste receptors.

    Science.gov (United States)

    Lazutkaite, Greta; Soldà, Alice; Lossow, Kristina; Meyerhof, Wolfgang; Dale, Nicholas

    2017-11-01

    Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety. Ca 2+ imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids. The downstream pathway of the responses was determined using ATP receptor antagonists and channel blockers. The receptors were characterized using mice lacking the Tas1r1 gene, as well as an mGluR4 receptor antagonist. Amino acids such as Arg, Lys, and Ala evoke Ca 2+ signals in tanycytes and evoke the release of ATP via pannexin 1 and CalHM1, which amplifies the signal via a P2 receptor dependent mechanism. Tanycytes from mice lacking the Tas1r1 gene had diminished responses to lysine and arginine but not alanine. Antagonists of mGluR4 greatly reduced the responses to alanine and lysine. Two receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  11. Hypothalamic digoxin, hemispheric chemical dominance, and eating behavior.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-08-01

    The isoprenoid pathway produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in eating disorders. The patterns were compared in those with right hemispheric and left hemispheric dominance. The serum HMG CoA reductase activity, RBC membrane Na+-K+ ATPase activity, serum digoxin, magnesium, tryptophan catabolites (serotonin, quinolinic acid, strychnine, and nicotine), and tyrosine catabolites (morphine, dopamine, and noradrenaline) were measured in anorexia nervosa, bulimia nervosa, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. Digoxin synthesis was increased with upregulated tryptophan catabolism and downregulated tyrosine catabolism in those with anorexia nervosa and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism and upregulated tyrosine catabolism in those with bulimia nervosa and left hemispheric chemical dominance. The membrane Na+-K+ ATPase activity and serum magnesium were decreased in anorexia nervosa and right hemispheric chemical dominance while they were increased in bulimia nervosa and left hemispheric chemical dominance. Hypothalamic digoxin and hemispheric chemical dominance play a central role in the regulation of eating behavior. Anorexia nervosa represents the right hemispheric chemically dominant/hyperdigoxinemic state and bulimia nervosa the left hemispheric chemically dominant/hypodigoxinemic state.

  12. Hypothalamic-pituitary-testicular system following testicular X-irradiation

    International Nuclear Information System (INIS)

    Verjans, H.L.; Eik-Nes, K.B.

    1976-01-01

    Testes of adult, male rats were exposed to a total dose of 1500 R of X-irradiation. Testicular weight decreased from day 8 after X-ray treatment. This decrease was, however, precded by an increment of the testis weight on day 4 following treatment. X-ray treatment of testes was associated with significant increase in serum FSH. Testicular irradiation had, however, no effect on ventral prostate and seminal vesicles weights. Serum testosterone increased only on day 1, 2 and 4 after irradiation, while serum LH levels tended to increase from day 8 post-irradiation. These changes were not significant, however, when compared with non-irradiated controls. At 7, 13 and 20 days following 1500 R of bilateral, testicular X-irradiation, the hypothalamic-pituitary unit was still capable of responding to exogenous gonadotrophin releasing factor. Serum FSH may in male rats be regulated at least partly by circulating steroids of testicular origin and partly by an unknown factor of non-interstitial cell nature. (author)

  13. Hypothalamic-Pituitary Function in Brain Death: A Review.

    Science.gov (United States)

    Nair-Collins, Michael; Northrup, Jesse; Olcese, James

    2016-01-01

    The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord. © The Author(s) 2014.

  14. Melatonin controls seasonal breeding by a network of hypothalamic targets

    DEFF Research Database (Denmark)

    Revel, Florent G; Masson-Pévet, Mireille; Pévet, Paul

    2009-01-01

    In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible for the sea......In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible...... for the seasonal timing of reproduction, but the anatomical substrates and the cellular mechanisms through which melatonin modulates seasonal functions remain imprecise. Recently, several genes have been identified as being regulated by the photoperiod in the brain of seasonal mammals. These genes are thought....../GPR54 system and to the RFamide-related peptides.Interestingly, these systems involve different hypothalamic nuclei, suggesting that several brain loci may be crucial for melatonin to regulate reproduction, and thus represent key starting points to identify the long-sought-after mode and site...

  15. Ginseng and the hypothalamic-pituitary control of stress.

    Science.gov (United States)

    Fulder, S J

    1981-01-01

    There are a group of so-called tonic remedies in Far Eastern medicine which are traditionally viewed as harmonizing or adjustive. Ginseng and eleutherococcus are the best known, and there is evidence that they increase arousal, stamina and stress resistance. We have attempted to explore the relationship between the behavioral and the stress effects, and to relate this to traditional concepts. In one series of experiments mice were given ginseng throughout their lifespan. At intervals their behavior response to mild stress was examined and found to be exaggerated compared to controls without ginseng. However, normal ambulatory behavior in the absence of stress was unaffected. A second series of experiments indicated that the binding of corticosteroid to certain brain regions was increased in adrenalectomized rats given ginseng saponin, compared to saline treated controls. This can be interpreted as a result of an increase in hypothalamic-pituitary-adrenal sensitivity caused by ginseng saponin. This is in accord with traditional concepts of the use of these remedies.

  16. Hypothalamic eIF2α Signaling Regulates Food Intake

    Directory of Open Access Journals (Sweden)

    Anne-Catherine Maurin

    2014-02-01

    Full Text Available The reversible phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α is a highly conserved signal implicated in the cellular adaptation to numerous stresses such as the one caused by amino acid limitation. In response to dietary amino acid deficiency, the brain-specific activation of the eIF2α kinase GCN2 leads to food intake inhibition. We report here that GCN2 is rapidly activated in the mediobasal hypothalamus (MBH after consumption of a leucine-deficient diet. Furthermore, knockdown of GCN2 in this particular area shows that MBH GCN2 activity controls the onset of the aversive response. Importantly, pharmacological experiments demonstrate that the sole phosphorylation of eIF2α in the MBH is sufficient to regulate food intake. eIF2α signaling being at the crossroad of stress pathways activated in several pathological states, our study indicates that hypothalamic eIF2α phosphorylation could play a critical role in the onset of anorexia associated with certain diseases.

  17. Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex

    Science.gov (United States)

    Remedios, Ryan; Kennedy, Ann; Zelikowsky, Moriel; Grewe, Benjamin F.; Schnitzer, Mark J.; Anderson, David J.

    2017-10-01

    All animals possess a repertoire of innate (or instinctive) behaviours, which can be performed without training. Whether such behaviours are mediated by anatomically distinct and/or genetically specified neural pathways remains unknown. Here we report that neural representations within the mouse hypothalamus, that underlie innate social behaviours, are shaped by social experience. Oestrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents. We used microendoscopy to image Esr1+ neuronal activity in the VMHvl of male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male versus female conspecifics. However, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific neuronal ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not to mount or attack conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual experience with a female was sufficient to promote the separation of male and female ensembles and to induce an attack response 24 h later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviours. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a ‘hard-wired’ system.

  18. Neonatal ghrelin programs development of hypothalamic feeding circuits

    Science.gov (United States)

    Steculorum, Sophie M.; Collden, Gustav; Coupe, Berengere; Croizier, Sophie; Lockie, Sarah; Andrews, Zane B.; Jarosch, Florian; Klussmann, Sven; Bouret, Sebastien G.

    2015-01-01

    A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and neurobiological contribution of ghrelin during development by specifically blocking ghrelin action during early postnatal development in mice. Ghrelin blockade in neonatal mice resulted in enhanced ARH neural projections and long-term metabolic effects, including increased body weight, visceral fat, and blood glucose levels and decreased leptin sensitivity. In addition, chronic administration of ghrelin during postnatal life impaired the normal development of ARH projections and caused metabolic dysfunction. Consistent with these observations, direct exposure of postnatal ARH neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these data reveal that ghrelin plays an inhibitory role in the development of hypothalamic neural circuits and suggest that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation. PMID:25607843

  19. Childhood Parental Loss and Adult Hypothalamic-Pituitary-Adrenal Function

    Science.gov (United States)

    Tyrka, Audrey R.; Wier, Lauren; Price, Lawrence H.; Ross, Nicole; Anderson, George M.; Wilkinson, Charles W.; Carpenter, Linda L.

    2009-01-01

    Background Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function which could predispose to the development of psychiatric disorders. Methods Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared to a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, a measure of parental care, sex, and age on the hormone responses to the Dex/CRH test. Results Parental loss was associated with increased cortisol responses to the test, particularly in males. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. ACTH responses to the Dex/CRH test did not differ significantly as a function of parental loss. Conclusions These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function. PMID:18339361

  20. Functional hypothalamic amenorrhea and its psychological correlates: a controlled comparison.

    Science.gov (United States)

    Pentz, Ivana; Nakić Radoš, Sandra

    2017-04-01

    The goal of the study was to examine differences between adolescents and young women with functional hypothalamic amenorrhea (FHA) and control groups in personality traits, eating attitudes and behaviours, and perception of parental behaviour. The FHA is stress-induced anovulation, both related to metabolic challenges, such as excessive exercise and malnutrition, and psychogenic challenges, such as perfectionism and poor coping strategies. Three groups of adolescents and young women participated in the study: the FHA group (N = 25), the organic anovulation group (N = 21) and the eumenorrheic group with regular menstrual cycle (N = 20). Questionnaires on multidimensional perfectionism, self-control methods, eating attitudes and behaviours and perception of parental behaviour were administered. A clinical interview (SCID) was conducted with each participant. The FHA group had higher levels of perfectionism traits, i.e. higher levels of concerns over mistakes and personal standards, compared to control groups. The FHA group did not engage in disordered eating behaviours more often in comparison with control groups, but reported more prevalent history of anorexia nervosa. The FHA group did not differ from controls in perception of parental rejection, emotional warmth or overprotection. The findings suggest that FHA can be characterised by the subtle psychological differences in personality traits, so the patients need to be diagnosed carefully.

  1. Retino-hypothalamic regulation of light-induced murine sleep

    Directory of Open Access Journals (Sweden)

    Fanuel eMuindi

    2014-08-01

    Full Text Available The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area and the suprachiasmatic nucleus. We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages.

  2. Hypothalamic endoplasmic reticulum stress of overtrained mice after recovery

    Directory of Open Access Journals (Sweden)

    Ana P. Pinto

    2017-05-01

    Full Text Available Abstract AIMS knowing the relationship between endoplasmic reticulum (ER stress and inflammation and based on the fact that downhill running-based overtraining (OT model increases hypothalamus levels of some pro-inflammatory cytokines, we verified the effects of three OT protocols on the levels of BiP, pIRE-1 (Ser734, pPERK (Thr981, pelF2alpha (Ser52, ATF-6 and GRP-94 proteins in the mouse hypothalamus after two weeks of recovery. METHODS the mice were randomized into control (CT, overtrained by downhill running (OTR/down, overtrained by uphill running (OTR/up and overtrained by running without inclination (OTR groups. After 2-week total recovery period (i.e., week 10, hypothalamus was removed and used for immunoblotting. RESULTS the OTR/down group exhibited high levels of BiP and ATF6. The other OT protocols showed higher levels of pPERK (Th981 and pelf-2alpha (Ser52 when compared with the CT group. CONCLUSION the current results suggest that after a 2-week total recovery period, the overtrained groups increased partially their ER stress protein levels, but without hypothalamic inflammation, which characterizes a physiological condition related to an adaptation mechanism.

  3. Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline.

    Science.gov (United States)

    Gordon, Catherine M; Ackerman, Kathryn E; Berga, Sarah L; Kaplan, Jay R; Mastorakos, George; Misra, Madhusmita; Murad, M Hassan; Santoro, Nanette F; Warren, Michelle P

    2017-05-01

    The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation. Copyright © 2017 Endocrine Society

  4. [A case of multiple sclerosis with hypothalamic amenorrhea].

    Science.gov (United States)

    Miyamoto, T; Miyamoto, M; Yokota, N; Kubo, J; Hirata, K

    2000-03-01

    We present a 31-year-old woman of multiple sclerosis. At age 28, she was admitted with complaints of echolalia and a gradual onset of weakness affecting the right upper and bilateral lower limbs. Brain MRI showed high intensity areas in the bilateral frontal gyri, lobuli paracentralis, and left anterior thalamus. Although she had been in remission for 3 years, she developed dysesthesia of left upper and lower limbs. Cervical T2 weighted MRI showed a new high signal intensity lesion in the spinal cord from the C2 to C3 level. The combination of the cerebral, thalamic and spinal cord lesions with remission and excerbations allowed the diagnosis of clinically MS to be made. She suffered amenorrhea from the onset of her illness. Serum prolactin was within the normal range. The LH and FSH basal secretions were decreased and there were low delayed secretions of LH and FSH after intravenous injection of 100 micrograms LHRH. We consider that her amenorrhea was caused by the hypothalamic lesion, supported by MR findings of dilatation of the third ventricle.

  5. Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations.

    Science.gov (United States)

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Warenik-Szymankiewicz, Alina; Genazzani, Andrea Riccardo

    2008-01-01

    Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA.

  6. ADHD-like behavior in a patient with hypothalamic hamartoma.

    Science.gov (United States)

    Katayama, Koujyu; Yamashita, Yushiro; Yatsuga, Shuichi; Koga, Yasutoshi; Matsuishi, Toyojiro

    2016-01-01

    We report a male patient with hypothalamic hamartoma (HH) who manifested central precocious puberty (CPP) at 4 years of age. Gonadotropin-releasing hormone (GnRH) analogue treatment was started at 6 years of age and his pubertal signs were suppressed. At 9 years of age, the patient was emotionally unstable, aggressive, and antisocial. He had severe attention deficit hyperactivity disorder (ADHD)-like behavior and conduct disorder. No seizure activity was observed. GnRH analogue treatment was discontinued for 8 months from 9 years and 4 months of age due to his mother's illness. During this period sexual urges were observed. Treatment with daily methylphenidate markedly improved his behavioral problems. However, his sexual urges were not suppressed until 3 months after the GnRH analogue treatment was restarted. The present case is unique because the patient's behavioral problems were observed despite the parahypothalamic type of HH and absence of seizures. This case is also rare because behavioral problems were observed without seizures, and no ADHD cases with hamartoma have been reported previously. Recently, clinical studies have described an association between psychiatric morbidity, including ADHD, and hyperandrogenism disorders. Our patient's ADHD-like symptoms might be due to hyperandrogenism. In such cases, GnRH analogue with methylphenidate could be effective for improving ADHD-like symptoms. Copyright © 2015. Published by Elsevier B.V.

  7. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

    Directory of Open Access Journals (Sweden)

    Wei eZhang

    2015-08-01

    Full Text Available Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis.

  8. A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

    Science.gov (United States)

    Kondoh, Y; Uemura, T; Murase, M; Yokoi, N; Ishikawa, M; Hirahara, F

    2001-10-01

    To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. Retrospective cohort study. Yokohama City University, Yokohama, Japan. Twenty-four women with progestin-negative hypothalamic amenorrhea. Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

  9. Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.

    Science.gov (United States)

    Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Kopchick, John J; List, Edward O; Berryman, Darlene E; Bartke, Andrzej; Miller, Richard A

    2015-12-01

    Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  10. Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids.

    Science.gov (United States)

    Choi, Sun Ju; Kim, Francis; Schwartz, Michael W; Wisse, Brent E

    2010-06-01

    Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1-7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P fatty acid (100, 250, or 500 microM for neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.

  11. Periventricular nodular and subcortical neuronal heterotopia in adult epileptic patients Heterotopía neuronal nodular y subcortical en pacientes adultos con epilepsia

    Directory of Open Access Journals (Sweden)

    Damián E. Consalvo

    2006-04-01

    Full Text Available Developmental malformations are brain abnormalities that occur during embryogenesis. Neuronal migration disorders, including heterotopic lesions, constitute one type of such abnormalities. The aim of the study was to compare the epileptic clinical patterns of patients with periventricular nodular heterotopia (PNH (G1 with those affected by subcortical heterotopia (SCH (G2 looking for differences between both groups which, eventually, might suggest the type of the underlying malformation. The variables studied in both groups were: type of the heterotopia depicted on MRI studies, sex, age, age at seizure onset, annual seizure frequency, localization of the ictal symptomatogenic zone, characteristics of the EEG, other associated anomalies on the magnetic resonance images (MRI besides the heterotopia, and response to treatment. The only difference found between both groups was the type of heterotopia as shown by MRI studies. The other assessed variables did not significantly (p>0.05 differ between groups. No differences in the clinical features characterizing epilepsy could be found in patients with PNH or SCH, being the images the only tool able to differentiate them.Las malformaciones de la corteza cerebral son un grupo de entidades que se producen durante las etapas del desarrollo embrionario y cuya manifestación clínica puede ser la epilepsia. Estas malformaciones pueden ser diagnosticadas in vivo a través de las imágenes por resonancia magnética (IRM. Un subtipo particular de éstas lo constituyen los trastornos en la migración neuronal, dentro de los cuales se ubican las heterotopías (HT. El objetivo del estudio fue comparar enfermos portadores de HT periventriculares (G1 con aquellos portadores de HT subcorticales (G2. Se analizaron las variables sexo, edad y edad de inicio de la epilepsia (EI en años, antecedentes familiares (AF o prenatales (AP, frecuencia anual de crisis (FAC y características semiológicas de las crisis

  12. Altered microstructural connectivity of the superior and middle cerebellar peduncles are related to motor dysfunction in children with diffuse periventricular leucomalacia born preterm: A DTI tractography study

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shanshan, E-mail: jelly_66@126.com; Fan, Guo Guang, E-mail: cjr.fanguoguang@vip.163.com; Xu, Ke, E-mail: cjr.xuke@vip.163.com; Wang, Ci, E-mail: xiangxuehai19850224@yahoo.cn

    2014-06-15

    Purpose: To investigate the microstructural integrity of superior cerebellar peduncles (SCP) and middle cerebellar peduncles (MCP) by using DTI tractography method, and further to detect whether the microstructural integrity of these major cerebellar pathways is related to motor function in children with diffuse periventricular leucomalacia (PVL) born preterm. Materials and methods: 46 children with diffuse PVL (30 males and 16 females; age range 3–48 months; mean age 22.4 ± 6.7 months; mean gestational age 30.5 ± 2.2 weeks) and 40 healthy controls (27 males and 13 females; age range 3.5–48 months; mean age 22.1 ± 5.8 months) were enrolled in this study. DTI outcome measurements, fractional anisotropy (FA), for the SCP, MCP and cortical spinal tract (CST) were calculated. The gross motor function classification system (GMFCS) was used for assessing motor functions. Results: Compared to the controls, patients with diffuse PVL had a significantly lower FA in bilateral SCP, MCP and CST. There was a significant negative correlation between GMFCS levels and FA in bilateral SCP, MCP and CST in the patients group. In addition, significant inverse correlation of FA value was found between not only the contralateral but also the ipsilateral CST and SCP/MCP. Conclusions: These findings suggest that the injury of SCP and MCP may contribute to the motor dysfunction of diffuse PVL. Moreover, the correlations we found between supratentorial and subtentorial injured white matter extend our knowledge about the cerebro-cerebellar white matter interaction in children with diffuse PVL.

  13. Altered microstructural connectivity of the superior and middle cerebellar peduncles are related to motor dysfunction in children with diffuse periventricular leucomalacia born preterm: A DTI tractography study

    International Nuclear Information System (INIS)

    Wang, Shanshan; Fan, Guo Guang; Xu, Ke; Wang, Ci

    2014-01-01

    Purpose: To investigate the microstructural integrity of superior cerebellar peduncles (SCP) and middle cerebellar peduncles (MCP) by using DTI tractography method, and further to detect whether the microstructural integrity of these major cerebellar pathways is related to motor function in children with diffuse periventricular leucomalacia (PVL) born preterm. Materials and methods: 46 children with diffuse PVL (30 males and 16 females; age range 3–48 months; mean age 22.4 ± 6.7 months; mean gestational age 30.5 ± 2.2 weeks) and 40 healthy controls (27 males and 13 females; age range 3.5–48 months; mean age 22.1 ± 5.8 months) were enrolled in this study. DTI outcome measurements, fractional anisotropy (FA), for the SCP, MCP and cortical spinal tract (CST) were calculated. The gross motor function classification system (GMFCS) was used for assessing motor functions. Results: Compared to the controls, patients with diffuse PVL had a significantly lower FA in bilateral SCP, MCP and CST. There was a significant negative correlation between GMFCS levels and FA in bilateral SCP, MCP and CST in the patients group. In addition, significant inverse correlation of FA value was found between not only the contralateral but also the ipsilateral CST and SCP/MCP. Conclusions: These findings suggest that the injury of SCP and MCP may contribute to the motor dysfunction of diffuse PVL. Moreover, the correlations we found between supratentorial and subtentorial injured white matter extend our knowledge about the cerebro-cerebellar white matter interaction in children with diffuse PVL

  14. MRI measurements of the pons and cerebellum in children born preterm; associations with the severity of periventricular leukomalacia and perinatal risk factors

    International Nuclear Information System (INIS)

    Argyropoulou, M.I.; Xydis, V.; Argyropoulou, P.I.; Efremidis, S.C.; Drougia, A.; Andronikou, S.; Tzoufi, M.; Bassounas, A.

    2003-01-01

    Our purpose was to measure the size of the pons and cerebellum in preterm babies with periventricular leukomalacia (PVL), and to study their relationship with the severity of PVL and with perinatal risk factors. We examined 33 premature children, mean gestational age 31 weeks, range 26-36 weeks with PVL on MRI, and 27 full-term controls. On MRI at 0.4-5.5 years (mean 1.4 years) we measured the area of the corpus callosum and vermis, the anteroposterior diameter of the pons and the volume of the cerebellum. The area of the corpus callosum was used as a marker of white matter loss and PVL severity. All regional brain measurements except that of the vermis were significantly lower in patients than controls: corpus callosum (mm 2 ): 239.6±92.5 vs 434.8±126.8, P 3 ): 68.2±31.6 vs 100.6±28.3, P 2 ): 808.1±292.2 vs 942.2±246.2, NS. Significant reduction in the area of the vermis: 411.3±203.3 vs 935±252.6 mm 2 ; cerebellar volume: 16.3±12.5 vs 96.6±20.2 mm 3 ; and the diameter of the pons: 10.1±2.2 vs 17.5±1.3 mm (P <0.01) were observed in seven children with gestational age ≤28 weeks, severe hypotension and large patent ductus arteriosus (PDA). There was a significant correlation between the duration of mechanical ventilation and the size of the vermis, pons and cerebellum (R=-0.65, -0.57 and -0.73, respectively, P <0.01). (orig.)

  15. Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved

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    Mohan Narayanan

    2015-09-01

    Full Text Available Microcephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infection or hypoxic ischemic encephalopathy, or be a part of a genetic syndrome. There are over 1000 conditions listed in OMIM (Online Mendelian Inheritance in Man where microcephaly is a key finding; many of these are associated with specific somatic features and non-CNS anomalies. The term primary microcephaly is used when microcephaly and delayed development are the primary features, and they are not part of another recognized syndrome.   In this case report, we present the clinical features of siblings (brother and sister with primary microcephaly and delayed development, and subtle dysmorphic features. Both children had brain MRI studies that showed periventricular and subcortical T2/FLAIR hyperintensities, without signs of white matter volume loss, and no parenchymal calcifications by CT scan. The family was enrolled in a research study for whole exome sequencing of probands and parents. Analysis of variants determined that the children were compound heterozygotes for nonsense mutations, c.277C>T (p.Arg93* and c.397C>T (p.Arg133*, in the TRMT10A gene. Mutations in this gene have only recently been reported in children with microcephaly and early onset diabetes mellitus.   Our report adds to current knowledge of TRMT10A related neurodevelopmental disorders and demonstrates imaging findings suggestive of delayed or abnormal myelination of the white matter in this disorder. Accurate diagnosis through genomic testing, as in the children described here, allows for early detection and management of medical complications, such as diabetes mellitus.

  16. VMN hypothalamic dopamine and serotonin in anorectic septic rats.

    Science.gov (United States)

    Torelli, G F; Meguid, M M; Miyata, G; Fetissov, S O; Carter, J L; Kim, H J; Muscaritoli, M; Rossi Fanelli, F

    2000-03-01

    During sepsis, catabolism of proteins and associated changes in plasma amino acids occur. Tryptophan and tyrosine, and their derivatives serotonin (5-HT) and dopamine (DA), influence hypothalamic feeding-related areas and are associated with the onset of anorexia. We hypothesized that anorexia of sepsis is associated with changes in serotonin and dopamine in the ventromedial nucleus (VMN) of the hypothalamus. The aim of this study was to test our hypothesis by measuring intra-VMN changes of these two neurotransmitters at the onset of anorexia during sepsis. Fischer 344 male rats had an intracerebral guide cannula stereotaxically implanted into the VMN. Ten days later, in awake, overnight-food-deprived rats, a microdialysis probe was inserted through the in situ VMN cannula. Two hours thereafter, serial baseline serotonin and dopamine concentrations were measured. Then cecal ligation and puncture to induce sepsis or a control laparotomy was performed under isoflurane anesthesia. VMN microdialysis samples were serially collected every 30 min for 8 h after the surgical procedure to determine 5-HT and DA changes in response to sepsis. During the hypermetabolic response to sepsis, a strong association occurred between anorexia and a significant reduction of VMN dopamine concentration (P anorexia of sepsis. Six hours after operation, a single meal was offered for 20 min to assess the response of neurotransmitters to food ingestion. Food intake was minimal in anorectic septic rats (mean size of the after food-deprived meal in the Septic group was 0.03+/-0.01 g, that of the Control group was 1.27+/-0.14 g; P = 0.0001), while Control rats demonstrated anticipated changes in neurotransmitters in response to eating. We conclude that the onset of anorexia in septic rats is associated with a reduction in VMN dopamine.

  17. Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing.

    Science.gov (United States)

    Le Foll, Christelle; Irani, Boman G; Magnan, Christophe; Dunn-Meynell, Ambrose A; Levin, Barry E

    2009-09-01

    We assessed the mechanisms by which specialized hypothalamic ventromedial nucleus (VMN) neurons utilize both glucose and long-chain fatty acids as signaling molecules to alter their activity as a potential means of regulating energy homeostasis. Fura-2 calcium (Ca(2+)) and membrane potential dye imaging, together with pharmacological agents, were used to assess the mechanisms by which oleic acid (OA) alters the activity of dissociated VMN neurons from 3- to 4-wk-old rats. OA excited up to 43% and inhibited up to 29% of all VMN neurons independently of glucose concentrations. In those neurons excited by both 2.5 mM glucose and OA, OA had a concentration-dependent effective excitatory concentration (EC(50)) of 13.1 nM. Neurons inhibited by both 2.5 mM glucose and OA had an effective inhibitory concentration (IC(50)) of 93 nM. At 0.5 mM glucose, OA had markedly different effects on these same neurons. Inhibition of carnitine palmitoyltransferase, reactive oxygen species formation, long-chain acetyl-CoA synthetase and ATP-sensitive K(+) channel activity or activation of uncoupling protein 2 (UCP2) accounted for only approximately 20% of OA's excitatory effects and approximately 40% of its inhibitory effects. Inhibition of CD36, a fatty acid transporter that can alter cell function independently of intracellular fatty acid metabolism, reduced the effects of OA by up to 45%. Thus OA affects VMN neuronal activity through multiple pathways. In glucosensing neurons, its effects are glucose dependent. This glucose-OA interaction provides a potential mechanism whereby such "metabolic sensing" neurons can respond to differences in the metabolic states associated with fasting and feeding.

  18. Rapid dopaminergic modulation of the fish hypothalamic transcriptome and proteome.

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    Jason T Popesku

    2010-08-01

    Full Text Available Dopamine (DA is a major neurotransmitter playing an important role in the regulation of vertebrate reproduction. We developed a novel method for the comparison of transcriptomic and proteomic data obtained from in vivo experiments designed to study the neuroendocrine actions of DA.Female goldfish were injected (i.p. with DA agonists (D1-specific; SKF 38393, or D2-specific; LY 171555 and sacrificed after 5 h. Serum LH levels were reduced by 57% and 75% by SKF 38393 and LY 171555, respectively, indicating that the treatments produced physiologically relevant responses in vivo. Bioinformatic strategies and a ray-finned fish database were established for microarray and iTRAQ proteomic analysis of the hypothalamus, revealing a total of 3088 mRNAs and 42 proteins as being differentially regulated by the treatments. Twenty one proteins and mRNAs corresponding to these proteins appeared on both lists. Many of the mRNAs and proteins affected by the treatments were grouped into the Gene Ontology categorizations of protein complex, signal transduction, response to stimulus, and regulation of cellular processes. There was a 57% and 14% directional agreement between the differentially-regulated mRNAs and proteins for SKF 38393 and LY 171555, respectively.The results demonstrate the applicability of advanced high-throughput genomic and proteomic analyses in an amendable well-studied teleost model species whose genome has yet to be sequenced. We demonstrate that DA rapidly regulates multiple hypothalamic pathways and processes that are also known to be involved in pathologies of the central nervous system.

  19. Management of optic pathway and chiasmatic-hypothalamic gliomas in children with radiation therapy

    International Nuclear Information System (INIS)

    Erkal, Haldun Suekrue; Serin, Meltem; Cakmak, Ahmet

    1997-01-01

    Background and purpose: Optic pathway and chiasmatic-hypothalamic gliomas are rare childhood tumors. This study presents the experience in management of these tumors with radiation therapy. Materials and methods: Thirty-three children with the diagnosis of optic pathway and chiasmatic-hypothalamic gliomas were treated with radiation therapy from 1973 through 1994 in the Department of Radiation Oncology at Ankara University Faculty of Medicine. Twenty-four children had optic pathway gliomas and nine had chiasmatic-hypothalamic gliomas. Evidence of neurofibromatosis was present in six children. Subtotal resection was performed in 22 children and a biopsy in seven. The most common prescription for total tumor dose was 50 Gy, delivered in 2 Gy daily fractions. Follow-up ranged from 0.5 to 16.1 years (mean, 13.6 years). Results: Overall, progression-free and cause-specific survival probabilities for the entire group were 93%, 82% and 93%, respectively, at 5 years and 79%, 77% and 88%, respectively, at 10 years. Differences in overall, progression-free and cause-specific survival probabilities between optic pathway and chiasmatic-hypothalamic gliomas were not statistically significant. Absence of evidence of neurofibromatosis correlated with significantly better progression-free and cause-specific survival probabilities. Conclusion: Radiation therapy is effective in stabilization or improvement of vision and prevention of tumor progression in both optic pathway and chiasmatic-hypothalamic gliomas

  20. Altered hypothalamic protein expression in a rat model of Huntington's disease.

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    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  1. Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning.

    Science.gov (United States)

    Begum, Ghazala; Stevens, Adam; Smith, Emma Bolton; Connor, Kristin; Challis, John R G; Bloomfield, Frank; White, Anne

    2012-04-01

    Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63% decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.

  2. Stereotaxic approach to hypothalamic nuclei of the shiba goat with radiographic monitoring

    International Nuclear Information System (INIS)

    Mori, Y.; Takeuchi, Y.; Shimada, M.; Hayashi, S.; Hoshino, K.

    1990-01-01

    Practical method was devised for precise approach to hypothalamic nuclei in the Shiba goat. A stereotaxic instrument and a brain atlas with stereotaxic coordinates were developed. For an accurate placement of probes into specific hypothalamic regions a radiographic method was employed in which radio-opaque material was injected into the lateral ventricle and the ventricular outline was depicted. A sagittal diagram showing the arrangement of hypothalamic nuclei in relation to the brain ventricular system was constructed from the transverse stereotaxic atlas. This diagram was revealed extremely useful in pinpointing the target on the radiographs of lateral view. Precision of this method was evaluated in female Shiba goats (n = 4) by comparing radiographically estimated positions of hypothalamic nuclei with those histologically determined. Despite of cranial variability among individual animals these two parameters matched well each other in all the nuclei examined. Furthermore, chronic cannulae were implanted into different hypothalamic structures of one goat and the accuracy of their placement was confirmed histologically. Thus, it was revealed that the stereotaxy by aid of radiography herein described was accurate enough to apply to various neuroendocrinological studies in the Shiba goat

  3. Chronic exercise reduces hypothalamic transforming growth factor-β1 in middle-aged obese mice.

    Science.gov (United States)

    Silva, Vagner R R; Katashima, Carlos K; Lenhare, Luciene; Silva, Carla G B; Morari, Joseane; Camargo, Rafael L; Velloso, Licio A; Saad, Mario A; da Silva, Adelino S R; Pauli, Jose Rodrigo; Ropelle, Eduardo Rochete

    2017-08-28

    Obesity and aging are associated with hypothalamic inflammation, hyperphagia and abnormalities in the thermogenesis control. It has been demonstrated that the association between aging and obesity induces hypothalamic inflammation and metabolic disorders, at least in part, through the atypical hypothalamic transforming growth factor-β (TGF-β1). Physical exercise has been used to modulate several metabolic parameters. Thus, the aim of this study was to evaluate the impact of chronic exercise on TGF-β1 expression in the hypothalamus of Middle-Aged mice submitted to a one year of high-fat diet (HFD) treatment. We observed that long-term of HFD-feeding induced hypothalamic TGF-β1 accumulation, potentiated the hypothalamic inflammation, body weight gain and defective thermogenesis of Middle-Aged mice when compared to Middle-Aged animals fed on chow diet. As expected, chronic exercise induced negative energy balance, reduced food consumption and increasing the energy expenditure, which promotes body weight loss. Interestingly, exercise training reduced the TGF-β1 expression and IkB-α ser32 phosphorylation in the hypothalamus of Middle-Aged obese mice. Taken together our study demonstrated that chronic exercise suppressed the TGF-β1/IkB-α axis in the hypothalamus and improved the energy homeostasis in an animal model of obesity-associated to aging.

  4. Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents

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    Sarah M Burke

    2014-05-01

    Full Text Available The odorous steroid androstadienone, a putative male chemo-signal, was previously reported to evoke sex differences in hypothalamic activation in adult heterosexual men and women. In order to investigate whether puberty modulated this sex difference in response to androstadienone we measured the hypothalamic responsiveness to this chemo-signal in 39 prepubertal and 41 adolescent boys and girls by means of functional magnetic resonance imaging. We then investigated whether 36 prepubertal children and 38 adolescents diagnosed with Gender Dysphoria (GD; DSM-5 exhibited sex-atypical (in accordance with their experienced gender, rather than sex-typical (in accordance with their natal sex hypothalamic activations during olfactory stimulation with androstadienone. We found that the sex difference in responsiveness to androstadienone was already present in prepubertal control children and thus likely developed during early perinatal development instead of during sexual maturation. Adolescent girls and boys with GD both responded remarkably like their experienced gender, thus sex-atypical. In contrast, prepubertal girls with GD showed neither a typically male nor female hypothalamic activation pattern and prepubertal boys with GD had hypothalamic activations in response to androstadienone that were similar to control boys, thus sex-typical. We present here a unique data set of boys and girls diagnosed with GD at two different developmental stages, showing that these children possess certain sex-atypical functional brain characteristics and may have undergone atypical sexual differentiation of the brain.

  5. Kisspeptin levels in idiopathic hypogonadotropic hypogonadism diagnosed male patients and its relation with glucose-insulin dynamic.

    Science.gov (United States)

    Öztin, Hasan; Çağıltay, Eylem; Çağlayan, Sinan; Kaplan, Mustafa; Akpak, Yaşam Kemal; Karaca, Nilay; Tığlıoğlu, Mesut

    2016-12-01

    Male hypogonadism is defined as the deficiency of testosterone or sperm production synthesized by testicles or the deficiency of both. The reasons for hypogonadism may be primary, meaning testicular or secondary, meaning hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons. Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing follicular stimulant hormone (FSH), mainly luteinizing hormone (LH). GnRH omitted is under the effect of many hormonal or stimulating factors. Kisspeptin is present in many places of the body, mostly in hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Kisspeptin has a suppressor effect on the metastasis of many tumors such as breast cancer and malign melanoma metastases, and is called "metastin" for this reason. Kisspeptin is a strong stimulant of GnRH. In idiopathic hypogonadotropic hypogonadism (IHH) etiology, there is gonadotropic hormone release indeficiency which cannot be clearly described. A total of 30 male hypogonatropic hypogonadism diagnosed patients over 30 years of age who have applied to Haydarpasa Education Hospital Endocrinology and Metabolic Diseases Service were included in the study. Compared to the control group, the effect of kisspeptin on male patients with hypogonatropic hypogonadism and on insulin resistance developing in hypogonadism patients was investigated in our study. A statistically significant difference was detected between average kisspeptin measurements of the groups (p hypogonadism and has less effect on insulin resistance.

  6. Hypothalamic pituitary abnormalities in tubercular meningitis at the time of diagnosis.

    Science.gov (United States)

    Dhanwal, Dinesh Kumar; Vyas, Anirudh; Sharma, Ashok; Saxena, Alpana

    2010-12-01

    Tubercular meningitis (TBM) is the most dreaded form of extra pulmonary tuberculosis associated with high morbidity and mortality. Various hypothalamic pituitary hormonal abnormalities have been reported to occur years after recovery from disease but there are no systematic studies in the literature to evaluate the pituitary hypothalamic dysfunction in patients with TBM at the time of presentation. Therefore, the present study was designed to evaluate hypothalamic pituitary abnormalities in newly diagnosed patients with TBM. Patient case series. This prospective study included 75 untreated adult patients with TBM diagnosed as "definite", "highly probable" and "probable" TBM by Ahuja's criteria and in clinical stage 1, 2 or 3 at the time of presentation to hospital. Basal hormonal profile was measured by electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH), follicular stimulating hormone (FSH), prolactin (PRL), thyrotropin (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4). All patients were subjected to MRI to image brain and hypothalamic pituitary axis and CT for adrenal glands. Thirty-two (42.7%) cases showed relative or absolute cortisol insufficiency. Twenty-three (30.7%) cases showed central hypothyroidism and 37 (49.3%) cases had hyperprolactinemia. No patient had evidence of diabetes insipidus. Multiple hormone deficiency was seen in 22 (29.3%) cases. MRI of hypothalamic pituitary axis using dynamic scanning and thin cuts revealed abnormalities in 10 (13.3%) of the cases. CT adrenal gland was normal in all the patients. Tubercular meningitis is associated with both hormonal and structural abnormalities in the hypothalamic pituitary axis at the time of diagnosis.

  7. Anti-aging drugs reduce hypothalamic inflammation in a sex-specific manner.

    Science.gov (United States)

    Sadagurski, Marianna; Cady, Gillian; Miller, Richard A

    2017-08-01

    Aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF-1 signals. Early-life exposure to GH by injection, or to nutrient restriction in the first 3 weeks of life, also modulate both lifespan and the pace of hypothalamic inflammation. Three drugs extend lifespan of UM-HET3 mice in a sex-specific way: acarbose (ACA), 17-α-estradiol (17αE2), and nordihydroguaiaretic acid (NDGA), with more dramatic longevity increases in males in each case. In this study, we examined the effect of these anti-aging drugs on neuro-inflammation in hypothalamus and hippocampus. We found that age-associated hypothalamic inflammation is reduced in males but not in females at 12 months of age by ACA and 17αE2 and at 22 months of age in NDGA-treated mice. The three drugs blocked indices of hypothalamic reactive gliosis associated with aging, such as Iba-1-positive microglia and GFAP-positive astrocytes, as well as age-associated overproduction of TNF-α. This effect was not observed in drug-treated female mice or in the hippocampus of the drug-treated animals. On the other hand, caloric restriction (CR; an intervention that extends the lifespan in both sexes) significantly reduced hypothalamic microglia and TNF-α in both sexes at 12 months of age. Together, these results suggest that the extent of drug-induced changes in hypothalamic inflammatory processes is sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity and that mimics the changes seen, in both sexes, of long-lived nutrient restricted or mutant mice. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  8. Metabolic Impact on the Hypothalamic Kisspeptin-Kiss1r Signaling Pathway

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    Fazal Wahab

    2018-03-01

    Full Text Available A large body of data has established the hypothalamic kisspeptin (KP and its receptor, KISS1R, as major players in the activation of the neuroendocrine reproductive axis at the time of puberty and maintenance of reproductive capacity in the adult. Due to its strategic location, this ligand-receptor pair acts as an integrator of cues from gonadal steroids as well as of circadian and seasonal variation-related information on the reproductive axis. Besides these cues, the activity of the hypothalamic KP signaling is very sensitive to the current metabolic status of the body. In conditions of energy imbalance, either positive or negative, a number of alterations in the hypothalamic KP signaling pathway have been documented in different mammalian models including nonhuman primates and human. Deficiency of metabolic fuels during fasting causes a marked reduction of Kiss1 gene transcript levels in the hypothalamus and, hence, decreases the output of KP-containing neurons. Food intake or exogenous supply of metabolic cues, such as leptin, reverses metabolic insufficiency-related changes in the hypothalamic KP signaling. Likewise, alterations in Kiss1 expression have also been reported in other situations of energy imbalance like diabetes and obesity. Information related to the body’s current metabolic status reaches to KP neurons both directly as well as indirectly via a complex network of other neurons. In this review article, we have provided an updated summary of the available literature on the regulation of the hypothalamic KP-Kiss1r signaling by metabolic cues. In particular, the potential mechanisms of metabolic impact on the hypothalamic KP-Kiss1r signaling, in light of available evidence, are discussed.

  9. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights.

    Science.gov (United States)

    Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence

    2018-04-01

    Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly

  10. Increased concentration of. cap alpha. - and. gamma. -endorphin in post mortem hypothalamic tissue of schizophrenic patients

    Energy Technology Data Exchange (ETDEWEB)

    Wiegant, V.M.; Verhoef, C.J.; Burbach, J.P.H.; de Wied, D.

    1988-01-01

    The concentrations of ..cap alpha..-, ..beta..- and ..gamma..-endorphin were determined by radioimmunoassay in HPLC fractionated extracts of post mortem hypothalamic tissue obtained from schizophrenic patients and controls. The hypothalamic concentration of ..cap alpha..- and ..gamma..-endorphin was significantly higher in patients than in controls. No difference was found in the concentration of ..beta..-endorphin, the putative precursor of ..cap alpha..- and ..gamma..-endorphins. These results suggest a deviant metabolism of ..beta..-endorphin in the brain of schizophrenic patients. Whether this phenomenon is related to the psychopathology, or is a consequence of ante mortem farmacotherapy, remains to be established.

  11. Effect of treatment modality on the hypothalamic-pituitary function of patients treated with radiation therapy for pituitary adenomas: Hypothalamic dose and endocrine outcomes.

    Directory of Open Access Journals (Sweden)

    Andrew eElson

    2014-04-01

    Full Text Available Background: Both fractionated external beam radiotherapy and single fraction radiosurgery for pituitary adenomas are associated with the risk of hypothalamic-pituitary (HP axis dysfunction.Objective: To analyze the effect of treatment modality (Linac, TomoTherapy, or Gamma Knife on hypothalamic dose and correlate these with HP-Axis deficits after radiotherapy.Methods:Radiation plans of patients treated postoperatively for pituitary adenomas using Linac-based 3D Conformal Radiotherapy (CRT (n=11, TomoTherapy-based Intensity Modulated Radiation Therapy (IMRT (n=10, or Gamma Knife Stereotactic Radiosurgery (SRS(n=12 were retrospectively reviewed. Dose to the hypothalamus was analyzed and postradiotherapy hormone function including growth hormone (GH, thyroid (TSH, adrenal (ACTH, prolactin (PRL, and gonadotropins (FSH/LH were assessed. Results:Post-radiation, 13 of 27 (48% patients eligible for analysis developed at least one new hormone deficit, of which 8 of 11 (72% occurred in the Linac group, 4 of 8 (50% occurred in the TomoTherapy group, and 1 of 8 (12.5% occurred in the Gamma Knife group. Compared with fractionated techniques, Gamma Knife showed improved hypothalamic sparing for DMax Hypo, and V12Gy. For fractionated modalities, TomoTherapy showed improved dosimetric characteristics over Linac-based treatment with hypothalamic DMean (44.8 Gy vs. 26.8 Gy p=0.02, DMax (49.8 Gy vs. 39.1 Gy p=0.04, and V12Gy (100% vs. 76% p=0.004.Conclusion:Maximal dosimetric avoidance of the hypothalamus was achieved using Gamma Knife-based radiosurgery followed by TomoTherapy-based IMRT, and Linac-based 3D conformal radiation therapy, respectively.

  12. Genetics Home Reference: periventricular heterotopia

    Science.gov (United States)

    ... of the two sex chromosomes . The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ...

  13. Prolactin-sensitive neurons express estrogen receptor-α and depend on sex hormones for normal responsiveness to prolactin.

    Science.gov (United States)

    Furigo, Isadora C; Kim, Ki Woo; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; de Alencar, Amanda; Pedroso, João A B; Metzger, Martin; Donato, Jose

    2014-05-30

    Estrogens and prolactin share important target tissues, including the gonads, brain, liver, kidneys and some types of cancer cells. Herein, we sought anatomical and functional evidence of possible crosstalk between prolactin and estrogens in the mouse brain. First, we determined the distribution of prolactin-responsive neurons that express the estrogen receptor α (ERα). A large number of prolactin-induced pSTAT5-immunoreactive neurons expressing ERα mRNA were observed in several brain areas, including the anteroventral periventricular nucleus, medial preoptic nucleus, arcuate nucleus of the hypothalamus, ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH), medial nucleus of the amygdala and nucleus of the solitary tract. However, although the medial preoptic area, periventricular nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus, retrochiasmatic area, dorsomedial subdivision of the VMH, lateral hypothalamic area, dorsomedial nucleus of the hypothalamus and ventral premammillary nucleus contained significant numbers of prolactin-responsive neurons, these areas showed very few pSTAT5-immunoreactive cells expressing ERα mRNA. Second, we evaluated prolactin sensitivity in ovariectomized mice and observed that sex hormones are required for a normal responsiveness to prolactin as ovariectomized mice showed a lower number of prolactin-induced pSTAT5 immunoreactive neurons in all analyzed brain nuclei compared to gonad-intact females. In addition, we performed hypothalamic gene expression analyses to determine possible post-ovariectomy changes in components of prolactin signaling. We observed no significant changes in the mRNA expression of prolactin receptor, STAT5a or STAT5b. In summary, sex hormones exert a permissive role in maintaining the brain's prolactin sensitivity, most likely through post-transcriptional mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Direct versus indirect actions of ghrelin on hypothalamic NPY neurons.

    Science.gov (United States)

    Hashiguchi, Hiroshi; Sheng, Zhenyu; Routh, Vanessa; Gerzanich, Volodymyr; Simard, J Marc; Bryan, Joseph

    2017-01-01

    Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices. Depolarization resulted from a decreased input resistance (IR) in ~70% of neurons (15/22) or an increased IR in the remainder (7/22), consistent with the opening or closing of ion channels, respectively. Although tetrodotoxin (TTX) blockade of presynaptic action potentials reduced ghrelin-induced changes in MP and IR, ghrelin still significantly depolarized the MP and decreased IR in TTX-treated neurons, suggesting that ghrelin directly opens cation channel(s) in NPY neurons. In isolated NPY-GFP neurons, ghrelin produced a sustained rise of [Ca2+]c, with an EC50 ~110 pM. Pharmacologic studies confirmed that the direct action of ghrelin was through occupation of the growth hormone secretagogue receptor, GHS-R, and demonstrated the importance of the adenylate cyclase/cAMP/protein kinase A (PKA) and phospholipase C/inositol triphosphate (PLC/IP3) pathways as activators of 5' AMP-activated protein kinase (AMPK). Activation of isolated neurons was not affected by CNQX or TTX, but reducing [Na+]o suppressed activation, suggesting a role for Na+-permeable cation channels. SUR1 and two channel partners, Kir6.2 and Trpm4, were identified immunologically in NPY-GFP neurons in situ. The actions of SUR1 and Trpm4 modulators were informative: like ghrelin, diazoxide, a SUR1 agonist, elevated [Ca2+]c and glibenclamide, a SUR1 antagonist, partially suppressed ghrelin action, while 9-phenanthrol and flufenamic acid, selective Trpm4 antagonists, blocked ghrelin actions on isolated neurons. Ghrelin activation was unaffected by nifedipine and

  15. Fluoxetine Induces Proliferation and Inhibits Differentiation of Hypothalamic Neuroprogenitor Cells In Vitro

    Science.gov (United States)

    Sousa-Ferreira, Lígia; Aveleira, Célia; Botelho, Mariana; Álvaro, Ana Rita; Pereira de Almeida, Luís; Cavadas, Cláudia

    2014-01-01

    A significant number of children undergo maternal exposure to antidepressants and they often present low birth weight. Therefore, it is important to understand how selective serotonin reuptake inhibitors (SSRIs) affect the development of the hypothalamus, the key center for metabolism regulation. In this study we investigated the proliferative actions of fluoxetine in fetal hypothalamic neuroprogenitor cells and demonstrate that fluoxetine induces the proliferation of these cells, as shown by increased neurospheres size and number of proliferative cells (Ki-67+ cells). Moreover, fluoxetine inhibits the differentiation of hypothalamic neuroprogenitor cells, as demonstrated by decreased number of mature neurons (Neu-N+ cells) and increased number of undifferentiated cells (SOX-2+ cells). Additionally, fluoxetine-induced proliferation and maintenance of hypothalamic neuroprogenitor cells leads to changes in the mRNA levels of appetite regulator neuropeptides, including Neuropeptide Y (NPY) and Cocaine-and-Amphetamine-Regulated-Transcript (CART). This study provides the first evidence that SSRIs affect the development of hypothalamic neuroprogenitor cells in vitro with consequent alterations on appetite neuropeptides. PMID:24598761

  16. Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.

    Science.gov (United States)

    Takahashi, Hiroyuki; Takata, Fuyuko; Matsumoto, Junichi; Machida, Takashi; Yamauchi, Atsushi; Dohgu, Shinya; Kataoka, Yasufumi

    2015-02-20

    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 β (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 β 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Spontaneous remission of chiasmatic/hypothalamic masses in neurofibromatosis type 1: report of two cases

    International Nuclear Information System (INIS)

    Gottschalk, S.; Tavakolian, R.; Lehmann, R.; Buske, A.; Tinschert, S.

    1999-01-01

    We report two children with neurofibromatosis type 1 showing enhancing masses on MRI suggesting neoplasms in the chiasm and hypothalamic region. In both patients no visual or endocrinal dysfunction was present. On serial MRI spontaneous partial remission was found, implying that a cautious approach to therapeutic management of similar cases should be taken. (orig.) (orig.)

  18. Childhood Craniopharyngioma with Hypothalamic Obesity - No Long-term Weight Reduction due to Rehabilitation Programs

    NARCIS (Netherlands)

    Sterkenburg, A. S.; Hoffmann, A.; Gebhardt, U.; Waldeck, E.; Springer, S.; Mueller, H. L.

    2014-01-01

    Background: Severe obesity due to hypothalamic involvement has major impact on prognosis in long-term survivors of childhood craniopharyngioma. The long-term effects of rehabilitation efforts on weight development and obesity in these patients are not analyzed up to now. Patients and Methods: 108

  19. Dehydration-induced release of vasopressin involves activation of hypothalamic histaminergic neurons.

    Science.gov (United States)

    Kjaer, A; Knigge, U; Rouleau, A; Garbarg, M; Warberg, J

    1994-08-01

    The hypothalamic neurotransmitter histamine (HA) induces arginine vasopressin (AVP) release when administered centrally. We studied and characterized this effect of HA with respect to receptor involvement. In addition, we studied the possible role of hypothalamic histaminergic neurons in the mediation of a physiological stimulus (dehydration) for AVP secretion. Intracerebroventricular administration of HA, the H1-receptor agonists 2(3-bromophenyl)HA and 2-thiazolylethylamine, or the H2-receptor agonists amthamine or 4-methyl-HA stimulated AVP secretion. The stimulatory action of HA on AVP was inhibited by pretreatment with the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine. Twenty-four hours of dehydration elevated the plasma osmolality from 298 +/- 3 to 310 +/- 3 mmol/liter and increased the plasma AVP concentration 4-fold. The hypothalamic content of HA and its metabolite tele-methyl-HA was elevated in response to dehydration, indicating an increased synthesis and release of hypothalamic HA. Dehydration-induced AVP secretion was lowered when neuronal HA synthesis was inhibited by the administration of (S) alpha-fluoromethylhistidine or when the animals were pretreated with the H3-receptor agonist R(alpha)methylhistamine, which inhibits the release and synthesis of HA, the H1-receptor antagonists mepyramine and cetirizine, or the H2-receptor antagonists cimetidine and ranitidine. We conclude that HA, via activation of both H1- and H2-receptors, stimulates AVP release and that HA is a physiological regulator of AVP secretion.

  20. Mechanisms underlying prorenin actions on hypothalamic neurons implicated in cardiometabolic control

    Directory of Open Access Journals (Sweden)

    Soledad Pitra

    2016-10-01

    Conclusions: We identified novel neuronal targets and cellular mechanisms underlying PR/PRR actions in critical hypothalamic neurons involved in cardiometabolic regulation. This fundamental mechanistic information regarding central PR/PRR actions is essential for the development of novel RAS-based therapeutic targets for the treatment of cardiometabolic disorders in obesity and hypertension.

  1. An indirect action contributes to c-fos induction in paraventricular hypothalamic nucleus by neuropeptide Y

    Science.gov (United States)

    Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively...

  2. Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence

    NARCIS (Netherlands)

    Laceulle, O.M.; Nederhof, Esther; van Aken, M.A.G.; Ormel, Johan

    2017-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during

  3. Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia

    NARCIS (Netherlands)

    Unmehopa, Unga A.; van Heerikhuize, Joop J.; Spijkstra, Wenda; Woods, John W.; Howard, Andrew D.; Zycband, Emanuel; Feighner, Scott D.; Hreniuk, Donna L.; Palyha, Oksana C.; Guan, Xiao-Ming; Macneil, Douglas J.; van der Ploeg, Lex H. T.; Swaab, Dick F.

    2005-01-01

    Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R

  4. Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia.

    NARCIS (Netherlands)

    Unmehopa, U.A.; Heerikhuize, J.J. van; Spijkstra, W.; Woods, J.W.; Howard, A.D.; Zycband, E.; Feighner, S.D.; Hreniuk, D.L.; Palyha, O.C.; Guan, X.-M.; MacNeil, D.J.; Ploeg, L.H.T.; Swaab, D.F.

    2005-01-01

    Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R

  5. Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

    Science.gov (United States)

    Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

    2015-01-01

    Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

  6. Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction : a case study

    NARCIS (Netherlands)

    van Breda, E.; Keizer, H.A.; Kuipers, H.; Wolffenbuttel, B.H.R.

    The data of the present case demonstrate that the abuse of androgenic anabolic steroids (AAS) may lead to serious health effects. Although most clinical attention is usually directed towards peripheral side effects, the most serious central side effect, hypothalamic-pituitary-dysfunction, is often

  7. Adaptive Response in Female Modeling of the Hypothalamic-pituitary-gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

  8. Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children

    Science.gov (United States)

    Lopez-Duran, Nestor L.; Olson, Sheryl L.; Hajal, Nastassia J.; Felt, Barbara T.; Vazquez, Delia M.

    2009-01-01

    The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to…

  9. An updated view of hypothalamic-vascular-pituitary unit function and plasticity.

    Science.gov (United States)

    Le Tissier, Paul; Campos, Pauline; Lafont, Chrystel; Romanò, Nicola; Hodson, David J; Mollard, Patrice

    2017-05-01

    The discoveries of novel functional adaptations of the hypothalamus and anterior pituitary gland for physiological regulation have transformed our understanding of their interaction. The activity of a small proportion of hypothalamic neurons can control complex hormonal signalling, which is disconnected from a simple stimulus and the subsequent hormone secretion relationship and is dependent on physiological status. The interrelationship of the terminals of hypothalamic neurons and pituitary cells with the vasculature has an important role in determining the pattern of neurohormone exposure. Cells in the pituitary gland form networks with distinct organizational motifs that are related to the duration and pattern of output, and modifications of these networks occur in different physiological states, can persist after cessation of demand and result in enhanced function. Consequently, the hypothalamus and pituitary can no longer be considered as having a simple stratified relationship: with the vasculature they form a tripartite system, which must function in concert for appropriate hypothalamic regulation of physiological processes, such as reproduction. An improved understanding of the mechanisms underlying these regulatory features has implications for current and future therapies that correct defects in hypothalamic-pituitary axes. In addition, recapitulating proper network organization will be an important challenge for regenerative stem cell treatment.

  10. Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis

    NARCIS (Netherlands)

    Dekkers, J. C.; Geenen, R.; Godaert, G. L.; Glaudemans, K. A.; Lafeber, F. P.; van Doornen, L. J.; Bijlsma, J. W.

    2001-01-01

    There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1

  11. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  12. Revised criteria for PCOS in WHO Group II anovulatory infertility – a revival of hypothalamic amenorrhoea?

    DEFF Research Database (Denmark)

    Lauritsen, Mette Petri; Pinborg, Anja; Loft, Anne

    2015-01-01

    OBJECTIVE: To evaluate revised criteria for polycystic ovarian morphology (PCOM) in the diagnosis of polycystic ovary syndrome (PCOS) in anovulatory infertility. DESIGN: Prospective cohort study. PATIENTS: WHO Group II anovulatory infertile women (n = 75). MEASUREMENTS: Clinical, sonographic......, but according to AMH levels, the ovaries remain multifollicular. PERSPECTIVES: A better distinction between hypothalamic amenorrhoea and PCOS could improve treatment strategies for anovulatory infertility....

  13. Hypothalamic gene expression of appetite regulators in a cancer-cachectic mouse model [Dataset 1

    NARCIS (Netherlands)

    Dwarkasing, Jvalini; Dijk, Francina J.; Boekschoten, Mark; Faber, Joyce; Argilès, Josep M.; Lavianio, Alessandro; Muller, Michael; Witkamp, Renger; Norren, van Klaske

    2013-01-01

    Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have

  14. Hypothalamic food intake regulation in a cancer-cachectic mouse model

    NARCIS (Netherlands)

    Dwarkasing, J.T.; Dijk, van M.; Dijk, F.J.; Boekschoten, M.V.; Faber, J.; Argiles, J.M.; Laviano, A.; Müller, M.R.; Witkamp, R.F.; Norren, van K.

    2014-01-01

    Background Appetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an

  15. Hypothalamic gene expression of appetite regulators in a cancer-cachectic mouse model [Dataset 2

    NARCIS (Netherlands)

    Dwarkasing, Jvalini; Dijk, Francina J.; Boekschoten, Mark; Faber, Joyce; Argilès, Josep M.; Lavianio, Alessandro; Muller, Michael; Witkamp, Renger; Norren, van Klaske

    2013-01-01

    Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have

  16. Single-session Gamma Knife radiosurgery for optic pathway/hypothalamic gliomas.

    Science.gov (United States)

    El-Shehaby, Amr M N; Reda, Wael A; Abdel Karim, Khaled M; Emad Eldin, Reem M; Nabeel, Ahmed M

    2016-12-01

    OBJECTIVE Because of their critical and central location, it is deemed necessary to fractionate when considering irradiating optic pathway/hypothalamic gliomas. Stereotactic fractionated radiotherapy is considered safer when dealing with gliomas in this location. In this study, the safety and efficacy of single-session stereotactic radiosurgery for optic pathway/hypothalamic gliomas were reviewed. METHODS Between December 2004 and June 2014, 22 patients with optic pathway/hypothalamic gliomas were treated by single-session Gamma Knife radiosurgery. Twenty patients were available for follow-up for a minimum of 1 year after treatment. The patients were 5 to 43 years (median 16 years) of age. The tumor volume was 0.15 to 18.2 cm 3 (median 3.1 cm 3 ). The prescription dose ranged from 8 to 14 Gy (median 11.5 Gy). RESULTS The mean follow-up period was 43 months. Five tumors involved the optic nerve only, and 15 tumors involved the chiasm/hypothalamus. Two patients died during the follow-up period. The tumors shrank in 12 cases, remained stable in 6 cases, and progressed in 2 cases, thereby making the tumor control rate 90%. Vision remained stable in 12 cases, improved in 6 cases, and worsened in 2 cases in which there was tumor progression. Progression-free survival was 83% at 3 years. CONCLUSIONS The initial results indicate that single-session Gamma Knife radiosurgery is a safe and effective treatment option for optic pathway/hypothalamic gliomas.

  17. The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord

    NARCIS (Netherlands)

    Luiten, P.G.M.; Horst, G.J. ter; Karst, H.; Steffens, A.B.

    1985-01-01

    By application of the anterograde transport technique of Phaseolus vulgaris leuco-agglutinin the descending autonomic projection of the paraventricular hypothalamic nucleus was investigated. The Phaseolus lectin technique allowed the detection of the cells of origin in the paraventricular PVN, the

  18. Childhood Craniopharyngioma with Hypothalamic Obesity - No Long-term Weight Reduction due to Rehabilitation Programs

    NARCIS (Netherlands)

    Sterkenburg, A. S.; Hoffmann, A.; Gebhardt, U.; Waldeck, E.; Springer, S.; Mueller, H. L.

    Background: Severe obesity due to hypothalamic involvement has major impact on prognosis in long-term survivors of childhood craniopharyngioma. The long-term effects of rehabilitation efforts on weight development and obesity in these patients are not analyzed up to now. Patients and Methods: 108

  19. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

    Directory of Open Access Journals (Sweden)

    Sainte-Rose Christian

    2009-04-01

    Full Text Available Abstract Background Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA. As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. Methods 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement, grade 1 (n = 8, compression without involvement, or grade 2 (n = 12, severe involvement. Results Despite having similar body mass indexes (BMI, the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, The data for the whole population before and 6–18 months after surgery showed increases in BMI (P Conclusion The hypothalamic involvement by the craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement.

  20. Oxytocin and Naltrexone Successfully Treat Hypothalamic Obesity in a Boy Post-Craniopharyngioma Resection.

    Science.gov (United States)

    Hsu, Eugenie A; Miller, Jennifer L; Perez, Francisco A; Roth, Christian L

    2018-02-01

    Hypothalamic obesity, a treatment-resistant condition common to survivors of craniopharyngioma (CP), is strongly associated with a poor quality of life in this population. Oxytocin (OT), a hypothalamic neuropeptide, has been shown to play a role in the regulation of energy balance and to have anorexigenic effects in animal studies. Naltrexone (NAL), an opiate antagonist, has been shown to deter hedonic eating and to potentiate OT's effects. In this parent-observed study, we tested the administration of intranasal OT for 10 weeks (phase 1), followed by a combination of intranasal OT and NAL for 38 weeks (phase 2) in a 13-year-old male with confirmed hypothalamic obesity and hyperphagia post-CP resection. Treatment resulted in 1) reduction in body mass index (BMI) z score from 1.77 to 1.49 over 10 weeks during phase 1; 2) reduction in BMI z score from 1.49 to 0.82 over 38 weeks during phase 2; 3) reduced hyperphagia during phases 1 and 2; 4) continued hedonic high-carbohydrate food-seeking in the absence of hunger during phases 1 and 2; and 5) sustained weight reduction during decreased parental monitoring and free access to unlocked food in the home during the last 10 weeks of phase 2. This successful intervention of CP-related hypothalamic obesity and hyperphagia by OT alone and in combination with NAL is promising for conducting future studies of this treatment-recalcitrant form of obesity. Copyright © 2017 Endocrine Society

  1. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5bet...

  2. Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression

    NARCIS (Netherlands)

    Wu, Xueyan; Balesar, R.A.; Lu, Jing; Farajnia, Sahar; Zhu, Qiongbin; Huang, Manli; Bao, Ai-Min; Swaab, D.F.

    2017-01-01

    In depression, disrupted circadian rhythms reflect abnormalities in the central circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN). Although many SCN neurons are said to be GABAergic, it was not yet known whether and how SCN GABA changes occur in the SCN in depression. We,

  3. Exercise protects against high-fat diet-induced hypothalamic inflammation

    NARCIS (Netherlands)

    Yi, Chun-Xia; Al-Massadi, Omar; Donelan, Elizabeth; Lehti, Maarit; Weber, Jon; Ress, Chandler; Trivedi, Chitrang; Müller, Timo D.; Woods, Stephen C.; Hofmann, Susanna M.

    2012-01-01

    Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing

  4. Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha

    NARCIS (Netherlands)

    Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P.; Li, Dan L.; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F.; Tschöp, Matthias H.; Clegg, Deborah J.

    2014-01-01

    High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha

  5. Exercise protects against high-fat diet-induced hypothalamic inflammation.

    Science.gov (United States)

    Yi, Chun-Xia; Al-Massadi, Omar; Donelan, Elizabeth; Lehti, Maarit; Weber, Jon; Ress, Chandler; Trivedi, Chitrang; Müller, Timo D; Woods, Stephen C; Hofmann, Susanna M

    2012-06-25

    Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing local production of specific interleukins and cytokines, and these in turn may further promote systemic metabolic disease. Whether or how this microglial activation can be averted or reversed is unknown. Since running exercise improves systemic metabolic health and has been found to promote neuronal survival as well as the recovery of brain functions after injury, we hypothesized that regular treadmill running may blunt the effect of western diet on hypothalamic inflammation. Using low-density lipoprotein receptor deficient (l dlr-/-) mice to better reflect human lipid metabolism, we first confirmed that microglial activation in the hypothalamus is severely increased upon exposure to a high-fat, or "western", diet. Moderate, but regular, treadmill running exercise markedly decreased hypothalamic inflammation in these mice. Furthermore, the observed decline in microglial activation was associated with an improvement of glucose tolerance. Our findings support the hypothesis that hypothalamic inflammation can be reversed by exercise and suggest that interventions to avert or reverse neuronal damage may offer relevant potential in obesity treatment and prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain)

    NARCIS (Netherlands)

    Bohus, B.; Wimersma Greidanus, T.B. van; Wied, D. de

    Behavioral and endocrine profiles were established of homozygous (HO-DI) and heterozygous (HE-DI) rats with hereditary hypothalamic diabetes insipidus in comparison to Wistar strain rats. HO-DI rats were inferior in acquiring and maintaining active and passive avoidance behavior. Behavioral deficits

  7. Hypothalamic obesity after treatment for craniopharyngioma: the importance of the home environment.

    Science.gov (United States)

    Meijneke, Ruud W H; Schouten-van Meeteren, Antoinette Y N; de Boer, Nienke Y; van Zundert, Suzanne; van Trotsenburg, Paul A S; Stoelinga, Femke; van Santen, Hanneke M

    2015-01-01

    Hypothalamic obesity after treatment for craniopharyngioma is a well-recognized, severe problem. Treatment of hypothalamic obesity is difficult and often frustrating for the patient, the parents and the professional care-giver. Because hypothalamic obesity is caused by an underlying medical disorder, it is often assumed that regular diet and exercise are not beneficial to reduce the extraordinarily high body mass index, and in fact, lifestyle interventions have been shown to be insufficient in case of extreme hypothalamic obesity. Nevertheless, it is important to realize that also in this situation, informal care delivered by the family and appropriate parenting styles are required to minimize the obesity problem. We present a case in which weight gain in the home situation was considered unstoppable, and a very early mortality due to complications of the severe increasing obesity was considered inevitable. A permissive approach toward food intake became leading with rapid weight increase since a restrictive lifestyle was considered a senseless burden for the child. By admission to our hospital for a longer period of time, weight reduction was realized, and the merely permissive approach could be changed into active purposeful care by adequate information, instruction, guidance and encouragement of the affected child and her parents. This case illustrates that, although this type of obesity has a pathological origin, parental and environmental influences remain of extreme importance.

  8. Mindful Parenting Predicts Mothers' and Infants' Hypothalamic-Pituitary-Adrenal Activity during a Dyadic Stressor

    Science.gov (United States)

    Laurent, Heidemarie K.; Duncan, Larissa G.; Lightcap, April; Khan, Faaiza

    2017-01-01

    Mindfulness in the parenting relationship has been proposed to help both parents and children better regulate stress, though this has not yet been shown at the physiological level. In this study, we tested relations between maternal mindfulness in parenting and both mothers' and their infants' hypothalamic-pituitary-adrenal (HPA) axis activity…

  9. Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents

    NARCIS (Netherlands)

    Burke, S.M.; Cohen-Kettenis, P.T.; Veltman, D.J.; Klink, D.T.; Bakker, J.

    2014-01-01

    The odorous steroid androstadienone, a putative male chemo-signal, was previously reported to evoke sex differences in hypothalamic activation in adult heterosexual men and women. In order to investigate whether puberty modulated this sex difference in response to androstadienone, we measured the

  10. Hypercortisolemia Is Associated with Severity of Bone Loss and Depression in Hypothalamic Amenorrhea and Anorexia Nervosa

    OpenAIRE

    Lawson, Elizabeth A.; Donoho, Daniel; Miller, Karen K.; Misra, Madhusmita; Meenaghan, Erinne; Lydecker, Janet; Wexler, Tamara; Herzog, David B.; Klibanski, Anne

    2009-01-01

    Context: Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are associated with low bone density, anxiety, and depression. Women with AN and HA have elevated cortisol levels. Significant hypercortisolemia, as in Cushing’s disease, causes bone loss. It is unknown whether anxiety and depression and/or cortisol dysregulation contribute to low bone density in AN or HA.

  11. Discrepancies between genital responses and subjective sexual function during testosterone substitution in women with hypothalamic amenorrhea

    NARCIS (Netherlands)

    Tuiten, A.; Laan, E.; Panhuysen, G.; Everaerd, W.; de Haan, E.; Koppeschaar, H.; Vroon, P.

    1996-01-01

    Psychosexual dysfunction is often suggested the cause of the disturbed eating habits associated with hypothalamic secondary amenorrhea. In contrast, we explored the possibility that impaired sexual function may result from reduced levels of testosterone in amenorrheic subjects as a consequence of

  12. Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use: the TRAILS study

    NARCIS (Netherlands)

    Prince van Leeuwen, A.; Creemers, H.E.; Greaves-Lord, K.; Verhulst, F.C.; Ormel, J.; Huizink, A.C.

    2011-01-01

    Aims: To investigate the relationship of life-time and repeated cannabis use with hypothalamic-pituitary-adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents. Design: Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco

  13. Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use : the TRAILS study

    NARCIS (Netherlands)

    van Leeuwen, Andrea Prince; Creemers, Hanneke E.; Greaves-Lord, Kirstin; Verhulst, Frank C.; Ormel, Johan; Huizink, Anja C.

    Aims To investigate the relationship of life-time and repeated cannabis use with hypothalamic-pituitary-adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents. Design Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco use

  14. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine

  15. The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

    NARCIS (Netherlands)

    P.C. Guest (Paul); D. Martins-de-Souza (Daniel); H. Rahmoune (Hassan); S. Bahn (Sabine); P.C. Guest (Paul)

    2013-01-01

    textabstractOver the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in

  16. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  17. Litter size variation in hypothalamic gene expression determines adult metabolic phenotype in Brandt's voles (Lasiopodomys brandtii.

    Directory of Open Access Journals (Sweden)

    Xue-Ying Zhang

    Full Text Available Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10-12 and small (3-4 litter sizes, of Brandt's voles (Lasiopodomys brandtii, a rodent species from Inner Mongolia grassland in China.Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3 mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP mRNA increased in the offspring from small litters.These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

  18. Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with postnatal nutritional environment.

    Directory of Open Access Journals (Sweden)

    Hui Chen

    Full Text Available OBJECTIVE: Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY and suppressor proopiomelanocortin (POMC in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD consumption are unclear. RESEARCH DESIGN AND METHODS: Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control. At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid metabolic markers were measured. RESULTS: Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain. CONCLUSIONS: Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanism. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring.

  19. Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamsters

    DEFF Research Database (Denmark)

    Ansel, L; Bolborea, M; Bentsen, A H

    2010-01-01

    ). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids...

  20. Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis.

    Science.gov (United States)

    Stark, Romana; Reichenbach, Alex; Andrews, Zane B

    2015-12-15

    The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin

  1. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    Directory of Open Access Journals (Sweden)

    Alvarez-Bolado Gonzalo

    2012-01-01

    Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly

  2. Participation of hypothalamic CB1 receptors in reproductive axis disruption during immune challenge.

    Science.gov (United States)

    Surkin, P N; Di Rosso, M E; Correa, F; Elverdin, J C; Genaro, A M; De Laurentiis, A; Fernández-Solari, J

    2017-08-01

    Immune challenge inhibits reproductive function and endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the eCB system mediates the inhibition of hormones that control reproduction as a result of immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on the hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated i.c.v. administration with a CB1 antagonist/inverse agonist (AM251) (500 ng/5 μL), followed by an i.p. injection of lipopolysaccharide (LPS) (5 mg/kg) 15 minutes later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 minutes post-LPS. The plasma concentration of tumour necrosis factor α and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 180 minutes post i.p. administration of LPS. However, cytokine mRNA expression in the hypothalamus increased only 180 minutes post-LPS, suggesting an inflammatory delay in this organ. CB1 receptor blockade with AM251 increased LPS inflammatory effects, particularly in the hypothalamus. LPS also inhibited the HPG axis by decreasing gonadotrophin-releasing hormone hypothalamic content and plasma levels of luteinising hormone and testosterone. These disruptor effects were accompanied by decreased hypothalamic Kiss1 mRNA expression and prostaglandin E2 content, as well as by increased gonadotrophin-inhibitory hormone (Rfrp3) mRNA expression. All these disruptive effects were prevented by the presence of AM251. In summary, our results suggest that, in male rats, eCB mediate immune challenge-inhibitory effects on reproductive axis at least partially via hypothalamic CB1 activation. In addition, this receptor also participates in homeostasis recovery by modulating the inflammatory process taking place after LPS

  3. Nutrient sensing and insulin signaling in neuropeptide-expressing immortalized, hypothalamic neurons: A cellular model of insulin resistance.

    Science.gov (United States)

    Fick, Laura J; Belsham, Denise D

    2010-08-15

    Obesity and type 2 diabetes mellitus represent a significant global health crisis. These two interrelated diseases are typified by perturbed insulin signaling in the hypothalamus. Using novel hypothalamic cell lines, we have begun to elucidate the molecular and intracellular mechanisms involved in the hypothalamic control of energy homeostasis and insulin resistance. In this review, we present evidence of insulin and glucose signaling pathways that lead to changes in neuropeptide gene expression. We have identified some of the molecular mechanisms involved in the control of de novo hypothalamic insulin mRNA expression. And finally, we have defined key mechanisms involved in the etiology of cellular insulin resistance in hypothalamic neurons that may play a fundamental role in cases of high levels of insulin or saturated fatty acids, often linked to the exacerbation of obesity and diabetes.

  4. The hypothalamic- pituitary -adrenal -leptin axis and metabolic health: A systems approach to resilience, robustness and control

    NARCIS (Netherlands)

    Aschbacher, K.; Rodriguez-Fernandez, M.; Wietmarschen, H. van; Tomiyama, A.; Jain, S.; Epel, E.; Doyle III, F.J.; Greef, J. van der

    2014-01-01

    Glucocorticoids contribute to obesity and metabolic syndrome; however, the mechanisms are unclear, and prognostic measures are unavailable. A systems level understanding of the hypothalamic-pituitary-adrenal (HPA) -leptin axis may reveal novel insights. Eighteen obese premenopausal women provided

  5. Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome

    NARCIS (Netherlands)

    A. Lukoshe (Akvile); Van Dijk, S.E. (Suzanne E.); G.E. van den Bosch (Gerbrich); A. van der Lugt (Aad); T.J.H. White (Tonya); A.C.S. Hokken-Koelega (Anita)

    2017-01-01

    textabstractBackground: Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional

  6. Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area – an anterograde tract-tracing study

    OpenAIRE

    Rege Sugárka Papp; Rege Sugárka Papp; Miklos ePalkovits; Miklos ePalkovits

    2014-01-01

    The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribu...

  7. Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area—an anterograde tract-tracing study

    OpenAIRE

    Papp, Rege S.; Palkovits, Miklós

    2014-01-01

    The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribu...

  8. Microglia Dictate the Impact of Saturated Fat Consumption on Hypothalamic Inflammation and Neuronal Function

    Directory of Open Access Journals (Sweden)

    Martin Valdearcos

    2014-12-01

    Full Text Available Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH. Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs, only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.

  9. Peculiarities of hypothalamic-pituitary thyroid function in children born from the Chornobyl NPP accident survivors

    International Nuclear Information System (INIS)

    Kopylova, O.V.; Stepanenko, O.A.

    2015-01-01

    The 168 children born to parents exposed after the Chernobyl accident were examined to study the hypothalamic-pituitary-thyroid system function in descendants of the Chernobyl survivors. Clinical, hormonal, ultrasound examinations and challenge test with tyroliberynum were conducted. Some abnormalities that might explain the functional strain of the hypothalamic-pituitary system were identified being of a great role in origination and progress of thyroid disease. The prolonged strain leads to decreased production of thyroid hormone, which causes an increased secretion of thyroid stimulating hormone. Under the influence of TSH the thyroid gland in the first stage becomes increased in its mass, which leads to the formation of endemic goiter. Stable and permanent thyroid gland enlargement often leads to formation of the nodular goiter and other proliferative processes, namely to carcinogenesis

  10. Cellular activation of hypothalamic hypocretin/orexin neurons facilitates short-term spatial memory in mice.

    Science.gov (United States)

    Aitta-Aho, Teemu; Pappa, Elpiniki; Burdakov, Denis; Apergis-Schoute, John

    2016-12-01

    The hypothalamic hypocretin/orexin (HO) system holds a central role in the regulation of several physiological functions critical for food-seeking behavior including mnemonic processes for effective foraging behavior. It is unclear however whether physiological increases in HO neuronal activity can support such processes. Using a designer rM3Ds receptor activation approach increasing HO neuronal activity resulted in improved short-term memory for novel locations. When tested on a non-spatial novelty object recognition task no significant difference was detected between groups indicating that hypothalamic HO neuronal activation can selectively facilitate short-term spatial memory for potentially supporting memory for locations during active exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy.

    Science.gov (United States)

    Inge, Thomas H; Pfluger, Paul; Zeller, Meg; Rose, Susan R; Burget, Lukas; Sundararajan, Sumana; Daniels, Stephen R; Tschöp, Matthias H

    2007-08-01

    A 14-year-old boy presented with daytime somnolence, intermittent emesis and hypothyroidism. Neuroimaging revealed a calcified suprasellar intracranial mass, suspected to be a craniopharyngioma. Subtotal resection of the tumor confirmed the diagnosis. Extreme obesity (BMI >60 kg/m(2)) and hyperinsulinemia followed tumor resection and cranial irradiation. Dietary interventions were unsuccessful, and pharmacologic intervention (i.e. octreotide) only slowed the rate of weight gain. Radiography documented the suprasellar mass. Following surgical resection and radiotherapy, hypothalamic-pituitary deficiencies were found. Preprandial and postprandial excursions of insulin, active ghrelin and leptin were measured before and after gastric bypass surgery. Panhypopituitarism, hypothalamic obesity and hyperinsulinemia following craniopharyngioma therapy. Severe caloric restriction, octreotide, and pituitary hormone replacement did not produce weight loss. Gastric bypass surgery led to reduced food cravings, significant weight loss, and amelioration of obesity-related comorbidities. Correction of fasting hyperinsulinemia, normalization of postprandial insulin responses, and reductions in active ghrelin and leptin concentrations were also observed.

  12. Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

    DEFF Research Database (Denmark)

    van Opstal, Anna M.; Akintola, Abimbola A.; Elst, Marjan van der

    2017-01-01

    The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this s......The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease...... effect. Our data provide proof of concept for future experiments testing the potential of intranasal application of insulin to ameliorate defective homeostatic control in patients with type 2 diabetes....

  13. Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity

    DEFF Research Database (Denmark)

    Andersson, Ulrika; Treebak, Jonas Thue; Nielsen, Jakob Nis

    2005-01-01

    . In recovery, glucose feeding increased plasma glucose and insulin concentrations whereas ghrelin and PYY decreased to (ghrelin) or below (PPY) resting levels. It is concluded that 1 h of strenuous exercise in rats does not elicit significant changes in hypothalamic AMPK activity despite an increase in plasma...... ghrelin. Thus, changes in energy metabolism during or after exercise are likely not coordinated by changes in hypothalamic AMPK activity.......Recent studies have demonstrated that AMP-activated protein kinase (AMPK) in the hypothalamus is involved in the regulation of food intake. Because exercise is known to influence appetite and cause substrate depletion, it may also influence AMPK in the hypothalamus. Male rats that either rested...

  14. The dorso-lateral recess of the hypothalamic ventricle in neonatal rats.

    Science.gov (United States)

    Menéndez, A; Alvarez-Uría, M

    1987-10-01

    Light and electron microscopy of the hypothalamic ventricle in neonatal rats demonstrate morphological specializations of the ventricular wall at the level of the premammillary region of the third ventricle. The morphological features are: (1) A ventricular recess that we have called the "hypothalamic dorso-lateral recess" (HDR). (2) The presence of intraventricular capillaries near the dorso-lateral recess. (3) The HDR possessing a specialized ependymal lining; this consists of non-ciliated cells with short microvilli and bleb-like processes. (4) The existence of cerebrospinal fluid-contacting neurons within the HDR. (5) The presence of numerous phagocytic supraependymal cells. The HDR is not found in adult rats. This indicates that the dorso-lateral recess may play a physiological role during development.

  15. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

    LENUS (Irish Health Repository)

    Dinan, Timothy G

    2012-02-03

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  16. Function of hypothalamic-hypophyseal-ovarian system in radiation treatment of patients with cervical cancer

    International Nuclear Information System (INIS)

    Modnikov, O.P.

    1984-01-01

    Radioimmunoassay of the hypothalamic-hypophyseal-ovarian interrelationships was performed in 87 patients with cervical cancer and 37 practically healthy women. The basal level of the follicle-stimulating hormone (ESH), luteinizing hormone (LH) and estradiol as well as their response to the administration of the releasing factor of the hypothalamus (luliberin) were studied. Some disorders that manifested thermselved in the decreased level of estradiol, were established in the patients with cervical cancer even before irradiation. Concomitant radiation therapy resulted in pronounced changes in the activities of the hypothalamic-hypophyseal-ovarian system that manifested themselves in the lowered rate of LH increment in response to the administration of luliberin and the absence of estradiol response to the load. These changes persisted long after the termination of concomitant radiation therapy

  17. Hypothalamic glucose-sensing: role of Glia-to-neuron signaling.

    Science.gov (United States)

    Tonon, M C; Lanfray, D; Castel, H; Vaudry, H; Morin, F

    2013-12-01

    The hypothalamus senses hormones and nutrients in order to regulate energy balance. In particular, detection of hypothalamic glucose levels has been shown to regulate both feeding behavior and peripheral glucose homeostasis, and impairment of this regulatory system is believed to be involved in the development of obesity and diabetes. Several data clearly demonstrate that glial cells are key elements in the perception of glucose, constituting with neurons a "glucose-sensing unit". Characterization of this interplay between glia and neurons represents an exciting challenge, and will undoubtedly contribute to identify new candidates for therapeutic intervention. The purpose of this review is to summarize the current data that stress the importance of glia in central glucose-sensing. The nature of the glia-to-neuron signaling is discussed, with a special focus on the endozepine ODN, a potent anorexigenic peptide that is highly expressed in hypothalamic glia. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Increased Hypothalamic Inflammation Associated with the Susceptibility to Obesity in Rats Exposed to High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Xiaoke Wang

    2012-01-01

    Full Text Available Inflammation has been implicated in the hypothalamic leptin and insulin resistance resulting defective food intake during high fat diet period. To investigate hypothalamic inflammation in dietary induced obesity (DIO and obesity resistant (DIO-R rats, we established rat models of DIO and DIO-R by feeding high fat diet for 10 weeks. Then we switched half of DIO and DIO-R rats to chow food and the other half to high fat diet for the following 8 weeks to explore hypothalamic inflammation response to the low fat diet intervention. Body weight, caloric intake, HOMA-IR, as well as the mRNA expression of hypothalamic TLR4, NF-κB, TNF-α, IL-1β, and IL-6 in DIO/HF rats were significantly increased compared to DIO-R/HF and CF rats, whereas IL-10 mRNA expression was lower in both DIO/HF and DIO-R/HF rats compared with CF rats. Switching to chow food from high fat diet reduced the body weight and improved insulin sensitivity but not affecting the expressions of studied inflammatory genes in DIO rats. Take together, upregulated hypothalamic inflammation may contribute to the overeating and development of obesity susceptibility induced by high fat diet. Switching to chow food had limited role in correcting hypothalamic inflammation in DIO rats during the intervention period.

  19. Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes*

    Science.gov (United States)

    Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

    2013-01-01

    Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID:24240094

  20. Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes.

    Science.gov (United States)

    Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

    2013-12-27

    Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance.

  1. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

    Directory of Open Access Journals (Sweden)

    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  2. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) Syndrome: A Case Report

    OpenAIRE

    Bagheri; Pourbakhtyaran; Talebi Kiasari; Taherkhanchi; Salarian; Sadeghi

    2016-01-01

    Introduction Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare disease. To date, there have been only few reported cases of ROHHAD syndrome. Case Presentation We report a 5-year-old- Iranian girl who had normal growth and development until her 4th year of life. At that time, the patient developed weight gain, constipation, coldness in the extremities, and hyperhidros...

  3. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake.

    Science.gov (United States)

    Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

    2015-01-01

    Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites) from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS) as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC) and agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,…), neurotransmitters and nutrients (glucose, lipids,…). The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes. In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  4. Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function.

    Science.gov (United States)

    Eachus, Helen; Bright, Charlotte; Cunliffe, Vincent T; Placzek, Marysia; Wood, Jonathan D; Watt, Penelope J

    2017-06-01

    Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that the role of DISC1 in stress responses is evolutionarily conserved and that DISC1 is essential for normal functioning of the HPI axis. Adult zebrafish homozygous mutant for disc1 show aberrant behavioural responses to stress. Our studies reveal that in the embryo, disc1 is expressed in neural progenitor cells of the hypothalamus, a conserved region of the vertebrate brain that centrally controls responses to environmental stressors. In disc1 mutant embryos, proliferating rx3+ hypothalamic progenitors are not maintained normally and neuronal differentiation is compromised: rx3-derived ff1b+ neurons, implicated in anxiety-related behaviours, and corticotrophin releasing hormone (crh) neurons, key regulators of the stress axis, develop abnormally, and rx3-derived pomc+ neurons are disorganised. Abnormal hypothalamic development is associated with dysfunctional behavioural and neuroendocrine stress responses. In contrast to wild type siblings, disc1 mutant larvae show altered crh levels, fail to upregulate cortisol levels when under stress and do not modulate shoal cohesion, indicative of abnormal social behaviour. These data indicate that disc1 is essential for normal development of the hypothalamus and for the correct functioning of the HPA/HPI axis. © The Author 2017. Published by Oxford University Press.

  5. Hypothalamic food intake regulation in a cancer-cachectic mouse model

    OpenAIRE

    Dwarkasing, Jvalini T.; van Dijk, Miriam; Dijk, Francina J.; Boekschoten, Mark V.; Faber, Joyce; Argilès, Josep M.; Laviano, Alessandro; Müller, Michael; Witkamp, Renger F.; van Norren, Klaske

    2013-01-01

    Background Appetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an increased food intake subsequently to the loss of body weight. We hypothesise that in this model, appetite-regulating systems in the hypothalamus, which apparently fail in anorexia, are still able t...

  6. Hypothalamic gene expression of appetite regulators in a cancer-cachectic mouse model [Dataset 2

    OpenAIRE

    Dwarkasing, Jvalini; Dijk, Francina J.; Boekschoten, Mark; Faber, Joyce; Argilès, Josep M.; Lavianio, Alessandro; Muller, Michael; Witkamp, Renger; Norren, van, Klaske

    2013-01-01

    Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still ab...

  7. Hypothalamic Gene Transfer of BDNF Inhibits Breast Cancer Progression and Metastasis in Middle Age Obese Mice

    OpenAIRE

    Liu, Xianglan; McMurphy, Travis; Xiao, Run; Slater, Andrew; Huang, Wei; Cao, Lei

    2014-01-01

    Activation of the hypothalamus-adipocyte axis is associated with an antiobesity and anticancer phenotype in animal models of melanoma and colon cancer. Brain-derived neurotrophic factor (BDNF) is a key mediator in the hypothalamus leading to preferential sympathoneural activation of adipose tissue and the ensuing resistance to obesity and cancer. Here, we generated middle age obese mice by high fat diet feeding for a year and investigated the effects of hypothalamic gene transfer of BDNF on a...

  8. Hypothalamic gene expression of appetite regulators in a cancer-cachectic mouse model [Dataset 1

    OpenAIRE

    Dwarkasing, Jvalini; Dijk, Francina J.; Boekschoten, Mark; Faber, Joyce; Argilès, Josep M.; Lavianio, Alessandro; Muller, Michael; Witkamp, Renger; Norren, van, Klaske

    2013-01-01

    Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still ab...

  9. Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance

    Science.gov (United States)

    Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben

    2015-01-01

    Objective Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Methods Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. Results The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca2+-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. Conclusions This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia. PMID:26909312

  10. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

    OpenAIRE

    Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

    2009-01-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of ...

  11. Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice.

    Science.gov (United States)

    Sefton, Charlotte; Harno, Erika; Davies, Alison; Small, Helen; Allen, Tiffany-Jayne; Wray, Jonathan R; Lawrence, Catherine B; Coll, Anthony P; White, Anne

    2016-11-01

    Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances.

  12. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)

    OpenAIRE

    Lee, Richard; Sawa, Akira

    2014-01-01

    In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

  13. Hypothalamic Neuroendocrine Correlates of Cutaneous Burn Injury in the Rat. I. Scanning Electron Microscopy

    Science.gov (United States)

    1986-01-01

    cat [9], the rabbit [51], The emergence of a large population of neurons into the subhuman primates [10-12, 24, 25, 38--41], and the human as cerebral...active sub- normal hypothalamic fetal neurografts into the third cerebral stances has been well documented in mammalian cerebro - ventricular lumen of...in trauma. 10. Coates, P. W. Responses of tanycytes in primate third ventricle In: Mamlmalian Terimngenexsis, chapter 9, edited by L. Girar- to

  14. Treatments to Prevent Bone Loss in Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis

    OpenAIRE

    Altayar, Osama; Al Nofal, Alaa; Carranza Leon, B. Gisella; Prokop, Larry J.; Wang, Zhen; Murad, M. Hassan

    2017-01-01

    Objective: We conducted a systematic review and meta-analysis of studies that evaluated the effect of hormonal therapy [estrogen therapy including oral contraceptive pills (OCP)] and bisphosphonates in preventing bone loss in patients with functional hypothalamic amenorrhea (FHA). Methods: We searched several electronic databases for controlled and noncontrolled studies that enrolled females of any age presenting with FHA (including athletic, weight loss, and stress-associated amenorrhea/olig...

  15. Hyperandrogenism in female athletes with functional hypothalamic amenorrhea: a distinct phenotype

    OpenAIRE

    Javed, Asma; Kashyap, Rahul; Lteif, Aida N

    2015-01-01

    Asma Javed,1 Rahul Kashyap,2 Aida N Lteif1 1Pediatric and Adolescent Medicine, Division of Pediatric Endocrinology Mayo Clinic, Rochester, MN, USA; 2Department of Anesthesia and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA Objective: To compare the reproductive, metabolic, and skeletal profiles of young athletic women with functional hypothalamic amenorrhea (FHA) as well as clinical or biochemical hyperandrogenism (FHA-EX+HA) with body mass index matched women with FHA due to exe...

  16. Functional hypothalamic amenorrhea and its influence on women’s health

    OpenAIRE

    Meczekalski, B.; Katulski, K.; Czyzyk, A.; Podfigurna-Stopa, A.; Maciejewska-Jeske, M.

    2014-01-01

    Introduction Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea. There are three types of FHA: weight loss-related, stress-related, and exercise-related amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). The final consequences are complex hormonal changes manifested by profound hypoes...

  17. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

    Science.gov (United States)

    Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

    2007-04-01

    Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether

  18. Function and Innervation of the Locus Ceruleus in a Macaque Model of Functional Hypothalamic Amenorrhea

    OpenAIRE

    Bethea, Cynthia L; Kim, Aaron; Cameron, Judy L

    2012-01-01

    A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afte...

  19. Effects of Oral Contraceptives on Natriuretic Peptide Levels in Women with Hypothalamic Amenorrhea: A Pilot Study

    OpenAIRE

    Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K.

    2011-01-01

    Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60 – 75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives increases natriuretic peptide levels and that end-of-study free testosterone levels are inversely associated with NT-proBNP levels, consistent with the hypothesis that ...

  20. For Debate: Should Bariatric Surgery be Performed in Children and Adolescents with Hypothalamic Obesity?

    Science.gov (United States)

    Stolbova, Sarka; Benes, Marek; Petruzelkova, Lenka; Lebl, Jan; Kolouskova, Stanislava

    2017-06-01

    Hypothalamic dysfunction leading to severe obesity is a serious long-term consequence of paediatric craniopharyngioma. It compromises quality of life, leads to long-term metabolic hazards, and may shorten life expectancy. Therefore, a proactive approach is required. Conventional treatment of hypothalamic obesity is difficult and hardly successful. Experience with bariatric surgery is limited, especially in younger patients. Two retrospective studies recently reported on classic bariatric surgery in a small series of individuals after craniopharyngioma. Of these, one included nine paediatric patients who underwent laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) or biliopancreatic diversion (BPD). The immediate effects were promising: The mean weight loss was 20.9 kilograms at 6 months and 15.1 kilograms at 12 months. A duodenal-jejunal bypass sleeve (DBJS; EndoBarrier) is a mini-invasive, endoscopically placed and fully reversible bariatric procedure. We reported a boy diagnosed with craniopharyngioma at 10 years old who underwent surgery and radiotherapy. His body weight increased to 139 kilograms and body mass index (BMI) to 46.1 kg/m2 (+4.0 SD) within the subsequent 4.5 years. Fifteen months after DJBS placement, he lost 32.8 kilograms, and his BMI dropped to 32.7 kg/m2 (+2.9 SD). Thus, DJBS proved to be a promising procedure in the treatment of hypothalamic obesity. We suggest performing it in children and adolescents with hypothalamic obesity to prevent or attenuate its devastating long-term sequelae. Copyright© of YS Medical Media ltd.

  1. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance

    OpenAIRE

    López, Miguel; Varela, Luis; Vázquez, María J; Rodríguez-Cuenca, Sergio; González, Carmen R; Velagapudi, Vidya R; Morgan, Donald A; Schoenmakers, Erik; Agassandian, Khristofor; Lage, Ricardo; de Morentin, Pablo Blanco Martínez; Tovar, Sulay; Nogueiras, Rubén; Carling, David; Lelliott, Christopher

    2010-01-01

    Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here, we demonstrate that either whole body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipog...

  2. Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

    Science.gov (United States)

    De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A

    2012-10-01

    Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

  3. Anorexia and Impaired Glucose Metabolism in Mice With Hypothalamic Ablation of Glut4 Neurons

    OpenAIRE

    Ren, Hongxia; Lu, Taylor Y.; McGraw, Timothy E.; Accili, Domenico

    2014-01-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin?mediated cell ablation to selectively remove basal hypothalamic Glut4 ...

  4. ERK1/2 mediates glucose-regulated POMC gene expression in hypothalamic neurons.

    Science.gov (United States)

    Zhang, Juan; Zhou, Yunting; Chen, Cheng; Yu, Feiyuan; Wang, Yun; Gu, Jiang; Ma, Lian; Ho, Guyu

    2015-04-01

    Hypothalamic glucose-sensing neurons regulate the expression of genes encoding feeding-related neuropetides POMC, AgRP, and NPY - the key components governing metabolic homeostasis. AMP-activated protein kinase (AMPK) is postulated to be the molecular mediator relaying glucose signals to regulate the expression of these neuropeptides. Whether other signaling mediator(s) plays a role is not clear. In this study, we investigated the role of ERK1/2 using primary hypothalamic neurons as the model system. The primary neurons were differentiated from hypothalamic progenitor cells. The differentiated neurons possessed the characteristic neuronal cell morphology and expressed neuronal post-mitotic markers as well as leptin-regulated orexigenic POMC and anorexigenic AgRP/NPY genes. Treatment of cells with glucose dose-dependently increased POMC and decreased AgRP/NPY expression with a concurrent suppression of AMPK phosphorylation. In addition, glucose treatment dose-dependently increased the ERK1/2 phosphorylation. Blockade of ERK1/2 activity with its specific inhibitor PD98059 partially (approximately 50%) abolished glucose-induced POMC expression, but had little effect on AgRP/NPY expression. Conversely, blockade of AMPK activity with its specific inhibitor produced a partial (approximately 50%) reversion of low-glucose-suppressed POMC expression, but almost completely blunted the low-glucose-induced AgRP/NPY expression. The results indicate that ERK1/2 mediated POMC but not AgRP/NPY expression. Confirming the in vitro findings, i.c.v. administration of PD98059 in rats similarly attenuated glucose-induced POMC expression in the hypothalamus, but again had little effect on AgRP/NPY expression. The results are indicative of a novel role of ERK1/2 in glucose-regulated POMC expression and offer new mechanistic insights into hypothalamic glucose sensing. © 2015 Society for Endocrinology.

  5. Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA).

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    Genazzani, Alessandro D; Despini, Giulia; Czyzyk, Adam; Podfigurna, Agnieszka; Simoncini, Tommaso; Meczekalski, Blazej

    2017-12-01

    Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12 weeks of LAC (250 mg/die) and l-carnitine (500 mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n = 27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.

  6. O uso da fontanela posterior no diagnóstico ultra-sonográfico das hemorragias periintraventriculares Use of posterior fontanelle in the ultrasound diagnosis of intraventricular/periventricular hemorrhage

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    Luciana D. V. Gauzzi

    2008-12-01

    Full Text Available OBJETIVO: Avaliar o uso da fontanela posterior em recém-nascidos prematuros (OBJECTIVE: To evaluate the use of the posterior fontanelle in premature neonates (< 37 weeks with a birth weight < 1,500 g in the ultrasound diagnosis of intraventricular/periventricular hemorrhage and to assess whether the use of the anterior fontanelle associated with the posterior fontanelle changes the interrater agreement. METHODS: Eighty-five premature neonates were evaluated in this prospective study. Ultrasound was performed using the anterior fontanelle, and later, the posterior fontanelle. A consensus diagnosis between two raters was used to analyze the agreement between the anterior fontanelle alone and in association with the posterior fontanelle. If there was no consensus, a third observer was involved to decide. RESULTS: Agreement between the first two raters had a kappa of 0.80 (95%CI 0.76-0.84. However, when the anterior fontanelle was evaluated alone, kappa was 0.74 (95%CI 0.70-0.78. Thirty-seven hemispheres had grade II hemorrhage, of which 17 (45.9% had their diagnosis performed using the anterior fontanelle; in 10 (27%, diagnosis was suspected by the anterior fontanelle and confirmed by the posterior fontanelle; and in 10 (27%, diagnosis was exclusively performed using the posterior fontanelle. Of the 454 hemispheres, in 20 (4.4% the diagnosis of intraventricular hemorrhage was performed exclusively by the posterior fontanelle (p < 0.001. CONCLUSIONS: In this study, the anterior fontanelle associated with the posterior fontanelle was better than the use of the anterior fontanelle alone in the identification of intraventricular/periventricular hemorrhage. Ultrasound using the posterior fontanelle allowed diagnosis of unsuspected grade II hemorrhage by the anterior fontanelle. Use of the posterior fontanelle was also useful to clarify presence of hemorrhage in inconclusive examinations by the anterior fontanelle.

  7. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

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    Trivin, Christine; Busiah, Kanetee; Mahlaoui, Nizar; Recasens, Christophe; Souberbielle, Jean-Claude; Zerah, Michel; Sainte-Rose, Christian; Brauner, Raja

    2009-01-01

    Background Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA). As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R) and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. Methods 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement), grade 1 (n = 8, compression without involvement), or grade 2 (n = 12, severe involvement). Results Despite having similar body mass indexes (BMI), the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement. PMID:19341477

  8. Hypothalamic peroxisome proliferator-activated receptor gamma regulates ghrelin production and food intake.

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    Li, Qingjie; Yu, Quan; Lin, Li; Zhang, Heng; Peng, Miao; Jing, Chunxia; Xu, Geyang

    2018-04-09

    Peroxisome proliferator-activated receptor-γ (PPARγ) regulates fatty acid storage, glucose metabolism, and food intake. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate appetite. However, the effects of PPARγ on ghrelin production are still unclear. In the present study, the effects of PPARγ on ghrelin production were examined in lean- or high-fat diet-induced obese (DIO) C57BL/6J mice and mHypoE-42 cells, a hypothalamic cell line. 3rd intracerebroventricular injection of adenoviral-directed overexpression of PPARγ (Ad-PPARγ) reduced hypothalamic and plasma ghrelin, food intake in both lean C57BL/6J mice and diet-induced obese mice. These changes were associated with a significant increase in mechanistic target of rapamycin complex 1 (mTORC1) activity. Overexpression of PPARγ enhanced mTORC1 signaling and suppressed ghrelin production in cultured mHypoE-42 cells. Our results suggest that hypothalamic PPARγ plays a vital role in ghrelin production and food intake in mice. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Developmental programming of hypothalamic neuronal circuits: impact on energy balance control

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    Gali Ramamoorthy, Thanuja; Begum, Ghazala; Harno, Erika; White, Anne

    2015-01-01

    The prevalence of obesity in adults and children has increased globally at an alarming rate. Mounting evidence from both epidemiological studies and animal models indicates that adult obesity and associated metabolic disorders can be programmed by intrauterine and early postnatal environment- a phenomenon known as “fetal programming of adult disease.” Data from nutritional intervention studies in animals including maternal under- and over-nutrition support the developmental origins of obesity and metabolic syndrome. The hypothalamic neuronal circuits located in the arcuate nucleus controlling appetite and energy expenditure are set early in life and are perturbed by maternal nutritional insults. In this review, we focus on the effects of maternal nutrition in programming permanent changes in these hypothalamic circuits, with experimental evidence from animal models of maternal under- and over-nutrition. We discuss the epigenetic modifications which regulate hypothalamic gene expression as potential molecular mechanisms linking maternal diet during pregnancy to the offspring's risk of obesity at a later age. Understanding these mechanisms in key metabolic genes may provide insights into the development of preventative intervention strategies. PMID:25954145

  10. Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children.

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    Shaikh, M Guftar; Grundy, Richard G; Kirk, Jeremy M W

    2008-12-01

    Obesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight. To investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO). This was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO). A total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (Pfasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood-brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.

  11. Role of Hypothalamic Melanocortin System in Adaptation of Food Intake to Food Protein Increase in Mice

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    Pillot, Bruno; Duraffourd, Céline; Bégeot, Martine; Joly, Aurélie; Luquet, Serge; Houberdon, Isabelle; Naville, Danielle; Vigier, Michèle; Gautier-Stein, Amandine; Magnan, Christophe; Mithieux, Gilles

    2011-01-01

    The hypothalamic melanocortin system—the melanocortin receptor of type 4 (MC4R) and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia), and agouti-related protein (AgRP, antagonist, inducing hyperphagia)—is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED) in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compared to mice fed on an isocaloric starch-enriched diet, there was a paradoxical decrease in expression of the hypothalamic proopiomelanocortin gene, precursor of α-MSH, and increase in expression of the gene encoding AgRP. The hypophagia effect of PED took place in mice with invalidation of either MC4R or POMC, and was even strengthened in mice with ablation of the AgRP-expressing neurons. These data strongly suggest that the hypothalamic melanocortin system does not mediate the hunger-curbing effects induced by changes in the macronutrient composition of food. Rather, the role of this system might be to defend the body against the variations in food intake generated by the nutritional environment. PMID:21544212

  12. Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice.

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    Bruno Pillot

    Full Text Available The hypothalamic melanocortin system--the melanocortin receptor of type 4 (MC4R and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia, and agouti-related protein (AgRP, antagonist, inducing hyperphagia--is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compared to mice fed on an isocaloric starch-enriched diet, there was a paradoxical decrease in expression of the hypothalamic proopiomelanocortin gene, precursor of α-MSH, and increase in expression of the gene encoding AgRP. The hypophagia effect of PED took place in mice with invalidation of either MC4R or POMC, and was even strengthened in mice with ablation of the AgRP-expressing neurons. These data strongly suggest that the hypothalamic melanocortin system does not mediate the hunger-curbing effects induced by changes in the macronutrient composition of food. Rather, the role of this system might be to defend the body against the variations in food intake generated by the nutritional environment.

  13. Developmental programming of hypothalamic neuronal circuits: impact on energy balance control

    Directory of Open Access Journals (Sweden)

    Thanuja eGali Ramamoorthy

    2015-04-01

    Full Text Available The prevalence of obesity in adults and children has increased globally at an alarming rate. Mounting evidence from both epidemiological studies and animal models indicates that adult obesity and associated metabolic disorders can be programmed by intrauterine and early postnatal environment- a phenomenon known as fetal programming of adult disease. Data from nutritional intervention studies in animals including maternal under- and over-nutrition support the developmental origins of obesity and metabolic syndrome. The hypothalamic neuronal circuits located in the arcuate nucleus controlling appetite and energy expenditure are set early in life and are perturbed by maternal nutritional insults. In this review, we focus on the effects of maternal nutrition in programming permanent changes in these hypothalamic circuits, with experimental evidence from animal models of maternal under- and over-nutrition. We discuss the epigenetic modifications which regulate hypothalamic gene expression as potential molecular mechanisms linking maternal diet during pregnancy to the offspring’s risk of obesity at a later age. Understanding these mechanisms in key metabolic genes may provide insights into the development of preventative intervention strategies.

  14. A sexually dimorphic hypothalamic response to chronic high-fat diet consumption.

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    Morselli, E; Frank, A P; Palmer, B F; Rodriguez-Navas, C; Criollo, A; Clegg, D J

    2016-02-01

    In this review, we discuss the observations that, following chronic high-fat diet (HFD) exposure, male mice have higher levels of saturated fatty acids (FAs) and total sphingolipids, whereas lower amounts of polyunsaturated FAs in the central nervous system (CNS) than females. Furthermore, males, when compared with female mice, have higher levels of inflammatory markers in the hypothalamus following exposure to HFD. The increase in markers of inflammation in male mice is possibly due to the reductions in proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and estrogen receptor alpha (ERα), which is not recapitulated in female mice. Consistently, hypothalamic inflammation is induced both in male and female ERα total-body knockout mice when exposed to a HFD, thus confirming the key role of ERα in the regulation of HFD-induced hypothalamic inflammation. Finally, the HFD-induced depletion of hypothalamic ERα is associated with dysregulation in metabolic homeostasis, as evidenced by reductions in glucose tolerance and decrements in myocardial function.

  15. Hypothalamic amenorrhea in a Camurati-Engelmann disease--a case report.

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    Meczekalski, Blazej; Czyzyk, Adam; Podfigurna-Stopa, Agnieszka; Rydzewski, Bogdan; Sroczynski, Jakub; Lipinska, Małgorzata; Sokalski, Jerzy; Krawczynski, Maciej; Jamsheer, Aleksander; Katulski, Krzysztof; Genazzani, Alessandro

    2013-05-01

    A case report of a patient diagnosed with Camurati-Engelmann Disease (CED) in association with the functional hypothalamic amenorrhea disturbances. CED is a very rare genetically determined disorder classified as a type of bone dysplasia. Case report. Department of Gynecological Endocrinology, 3rd grade Medical University Hospital. Twenty-one years old female patient with CED admitted to the hospital because of primary amenorrhea. Her history revealed skeletal deformities and hearing impairment. Clinical examination, ultrasound, laboratory evaluations (including serum gonadotropins (FSH, LH) at basal state and after stimulation with gonadotropin-releasing hormone, serum basal estradiol) radiological studies (X-ray of the head, the lumbar spine and lower extremities; a computed tomography of the head), G-banding karyotype, polymerase chain reaction and DNA sequencing. Hormonal serum evaluations were made using an enzyme-linked immunosorbent assay. The exon 4 of the transforming growth factor beta 1 gene was amplified by a polymerase chain reaction and the product was directly sequenced. The hormonal analysis was characteristic for the hypogonadotropic hypogonadism. Radiological and molecular analyses confirmed CED diagnosis. The hypothalamic amenorrhea in a patient with CED may be explained as a consequence of fat hypotrophy and very low body mass index. Therefore, impairment within hypothalamic-pituitary axis in patients with CED should be treated with special attention.

  16. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

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    Allison eGraebner

    2015-08-01

    Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

  17. NEUROANATOMICAL ASSOCIATION OF HYPOTHALAMIC HSD2-CONTAINING NEURONS WITH ERα, CATECHOLAMINES, OR OXYTOCIN: IMPLICATIONS FOR FEEDING?

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    Maegan L. Askew

    2015-06-01

    Full Text Available This study used immunohistochemical methods to investigate the possibility that hypothalamic neurons that contain 11-β-hydroxysteroid dehydrogenase type 2 (HSD2 are involved in the control of feeding by rats via neuroanatomical associations with the α subtype of estrogen receptor (ERα, catecholamines, and/or oxytocin. An aggregate of HSD2-containing neurons is located laterally in the hypothalamus, and the numbers of these neurons were greatly increased by estradiol treatment in ovariectomized rats compared to numbers in male rats and in ovariectomized rats that were not given estradiol. However, HSD2-containing neurons were anatomically segregated from ERα-containing neurons in the Ventromedial Hypothalamus and the Arcuate Nucleus. There was an absence of oxytocin-immunolabeled fibers in the area of HSD2-labeled neurons. Taken together, these findings provide no support for direct associations between hypothalamic HSD2 and ERα or oxytocin neurons in the control of feeding. In contrast, there was catecholamine-fiber labeling in the area of HSD2-labeled neurons, and these fibers occasionally were in close apposition to HSD2-labeled neurons. Therefore, we cannot rule out interactions between HSD2 and catecholamines in the control of feeding; however, given the relative sparseness of the appositions, any such interaction would appear to be modest. Thus, these studies do not conclusively identify a neuroanatomical substrate by which HSD2-containing neurons in the hypothalamus may alter feeding, and leave the functional role of hypothalamic HSD2-containing neurons subject to further investigation.

  18. Developmental changes in hypothalamic oxytocin and oxytocin receptor mRNA expression and their sensitivity to fasting in male and female rats.

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    Matsuzaki, Toshiya; Iwasa, Takeshi; Munkhzaya, Munkhsaikhan; Tungalagsuvd, Altankhuu; Kawami, Takako; Murakami, Masahiro; Yamasaki, Mikio; Yamamoto, Yuri; Kato, Takeshi; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2015-04-01

    Oxytocin (OT) affects the central nervous system and is involved in a variety of social and non-social behaviors. Recently, the role played by OT in energy metabolism and its organizational effects on estrogen receptor alpha (ER-α) during the neonatal period have gained attention. In this study, the developmental changes in the hypothalamic mRNA levels of OT, the OT receptor (OTR), and ER-α were evaluated in male and female rats. In addition, the fasting-induced changes in the hypothalamic mRNA levels of OT and the OTR were evaluated. Hypothalamic explants were taken from postnatal day (PND) 10, 20, and 30 rats, and the mRNA level of each molecule was measured. Hypothalamic OT mRNA expression increased throughout the developmental period in both sexes. The rats' hypothalamic OTR mRNA levels were highest on PND 10 and decreased throughout the developmental period. In the male rats, the hypothalamic mRNA levels of ER-α were higher on PND 30 than on PND 10. On the other hand, no significant differences in hypothalamic ER-α mRNA expression were detected among the examined time points in the female rats, although hypothalamic ER-α mRNA expression tended to be higher on PND 30 than on PND 10. Significant positive correlations were detected between hypothalamic OT and ER-α mRNA expression in both the male and female rats. Hypothalamic OT mRNA expression was not affected by fasting at any of the examined time points in either sex. These results indicate that hypothalamic OT expression is not sensitive to fasting during the developmental period. In addition, as a positive correlation was detected between hypothalamic OT and ER-α mRNA expression, these two molecules might interact with each other to induce appropriate neuronal development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Changes in the responsiveness of hypothalamic PK2 and PKR1 gene expression to fasting in developing male rats.

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    Iwasa, Takeshi; Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Kawami, Takako; Yamasaki, Mikio; Murakami, Masahiro; Kato, Takeshi; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2014-11-01

    Prokineticin (PK2) and its receptors (PKRs) are expressed in several regions of the central nervous system, including the hypothalamus. It has been reported that PK2 inhibits food intake via PKR1 and that the hypothalamic PK2 mRNA levels of adult rodents were reduced by food deprivation. However, some hypothalamic factors do not exhibit sensitivity to undernutrition in the early neonatal period, but subsequently become sensitive to it during the neonatal to pre-pubertal period. In this study, we investigated the changes in the sensitivity of hypothalamic PK2 and PKR1 mRNA expression to fasting during the developmental period in male rats. Under the fed conditions, the rats' hypothalamic PK2 and/or PKR1 mRNA levels were higher on postnatal day (PND) 10 than on PND20 or PND30. In addition, the hypothalamic PK2 and/or PKR1 mRNA levels of the male rats were higher than those of the females at all examined ages (PND10, 20, and 30). Hypothalamic PK2 mRNA expression was decreased by 24h fasting at PND10 and 30, but not at PND20. In addition, hypothalamic PKR1 mRNA expression was decreased by 24h fasting at PND10, but not at PND20 or 30. These results indicate that both PK2 and PKR1 are sensitive to nutritional status in male rats and that this sensitivity has already been established by the early neonatal period. It can be speculated that the PK2 system might compensate for the immaturity of other appetite regulatory factors in the early neonatal period. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  20. Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice.

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    Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

    2012-09-01

    Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

  1. Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia.

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    Tsunekawa, Taku; Banno, Ryoichi; Mizoguchi, Akira; Sugiyama, Mariko; Tominaga, Takashi; Onoue, Takeshi; Hagiwara, Daisuke; Ito, Yoshihiro; Iwama, Shintaro; Goto, Motomitsu; Suga, Hidetaka; Sugimura, Yoshihisa; Arima, Hiroshi

    2017-02-01

    Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT). In hypothalamic organotypic cultures, incubation with TNFα led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Hepatopulmonary syndrome caused by hypothalamic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma: a case report

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    Dai Jung

    2018-03-01

    Full Text Available Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD and diabetes mellitus (DM. We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection. Two years later, the craniopharyngioma recurred, and she underwent a second resection. Three years after her second operation, she was diagnosed with type 2 DM, after which she did not visit the outpatient clinic for 2 years and then suddenly reappeared with a weight loss of 25.8 kg that had occurred over 21 months. One month later, she presented to the Emergency Department with dyspnea. Laboratory findings revealed liver dysfunction and hypoxia with increased alveolar artery oxygen gradient. Liver biopsy showed portal hypertension and micronodular cirrhosis. Echocardiography and a lung perfusion scan demonstrated a right to left shunt. She was finally diagnosed with hepatopulmonary syndrome and is currently awaiting a donor for liver transplantation. Patients surviving craniopharyngioma need to be followed up carefully to detect signs of hypothalamic obesity and monitored for the development of other comorbidities such as DM, NAFLD, and hepatopulmonary syndrome.

  3. Hepatopulmonary syndrome caused by hypothalamic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma: a case report.

    Science.gov (United States)

    Jung, Dai; Seo, Go Hun; Kim, Yoon-Myung; Choi, Jin-Ho; Yoo, Han-Wook

    2018-03-01

    Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM). We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection. Two years later, the craniopharyngioma recurred, and she underwent a second resection. Three years after her second operation, she was diagnosed with type 2 DM, after which she did not visit the outpatient clinic for 2 years and then suddenly reappeared with a weight loss of 25.8 kg that had occurred over 21 months. One month later, she presented to the Emergency Department with dyspnea. Laboratory findings revealed liver dysfunction and hypoxia with increased alveolar artery oxygen gradient. Liver biopsy showed portal hypertension and micronodular cirrhosis. Echocardiography and a lung perfusion scan demonstrated a right to left shunt. She was finally diagnosed with hepatopulmonary syndrome and is currently awaiting a donor for liver transplantation. Patients surviving craniopharyngioma need to be followed up carefully to detect signs of hypothalamic obesity and monitored for the development of other comorbidities such as DM, NAFLD, and hepatopulmonary syndrome.

  4. Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia

    Directory of Open Access Journals (Sweden)

    Taku Tsunekawa

    2017-02-01

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD, remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3 was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT. In hypothalamic organotypic cultures, incubation with TNFα led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions.

  5. Reproductive responses of male Brandt's voles (Lasiopodomys brandtii) to 6-methoxybenzoxazolinone (6-MBOA) under short photoperiod.

    Science.gov (United States)

    Dai, Xin; Jiang, Lian Yu; Han, Mei; Ye, Man Hong; Wang, Ai Qin; Wei, Wan Hong; Yang, Sheng Mei

    2016-04-01

    The plant secondary metabolite 6-methoxybenzoxazolinone (6-MBOA) can stimulate and enhance animal reproduction. This compound has been successfully detected in Leymus chinensis, which is the main diet of Brandt's voles. The aim of this study was to investigate the effect of different 6-MBOA doses on the reproductive physiology of male Brandt's voles under a short photoperiod. The results showed that 6-MBOA administration increased relative testis weight, regardless of the dose, but it had little effect on the body mass. Low and middle doses of 6-MBOA increased the concentrations of luteinizing hormone and testosterone in the serum and the mRNA levels of StAR and CYP11a1 in the testes. However, 6-MBOA did not cause any significant increase in the mRNA levels of KiSS-1, GPR54, and GnRH compared to those in the control group. The mRNA level of KiSS-1 in the arcuate nucleus (ARC) was higher than that in the anteroventral periventricular nucleus (AVPV). Collectively, our results demonstrated that the number of KiSS-1-expressing neurons located in the ARC was the highest, and that 6-MBOA, which might modulate the reproductive activity along the hypothalamic-pituitary-gonadal axis, had a dose-dependent stimulatory effect on the reproductive activity of Brandt's voles under a short photoperiod. Our study provided insights into the mechanism of 6-MBOA action and the factors influencing the onset of reproduction in Brandt's voles.

  6. Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice

    Directory of Open Access Journals (Sweden)

    Anne K. McGavigan

    2017-03-01

    Full Text Available Bariatric surgery, such as vertical sleeve gastrectomy (VSG, causes remarkable improvements in cardiometabolic health, including hypertension remission. However, the mechanisms responsible remain undefined and poorly studied. Therefore, we developed and validated the first murine model of VSG that recapitulates the blood pressure-lowering effect of VSG using gold-standard radiotelemetry technology. We used this model to investigate several potential mechanisms, including body mass, brain endoplasmic reticulum (ER stress signaling and brain inflammatory signaling, which are all critical contributors to the pathogenesis of obesity-associated hypertension. Mice fed on a high-fat diet underwent sham or VSG surgery and radiotelemeter implantation. Sham mice were fed ad libitum or were food restricted to match their body mass to VSG-operated mice to determine the role of body mass in the ability of VSG to lower blood pressure. Blood pressure was then measured in freely moving unstressed mice by radiotelemetry. VSG decreased energy intake, body mass and fat mass. Mean arterial blood pressure (MAP was reduced in VSG-operated mice compared with both sham-operated groups. VSG-induced reductions in MAP were accompanied by a body mass-independent decrease in hypothalamic ER stress, hypothalamic inflammation and sympathetic nervous system tone. Assessment of gut microbial populations revealed VSG-induced increases in the relative abundance of Gammaproteobacteria and Enterococcus, and decreases in Adlercreutzia. These results suggest that VSG reduces blood pressure, but this is only partly due to the reduction in body weight. VSG-induced reductions in blood pressure may be driven by a decrease in hypothalamic ER stress and inflammatory signaling, and shifts in gut microbial populations.

  7. Reassessment of LRF radioimmunoassay in the plasma and hypothalamic extracts of rats and rams

    International Nuclear Information System (INIS)

    Caraty, A.; Reviers, M.-M. de; Pelletier, J.; Dubois, M.P.

    1980-01-01

    A highly sensitive and specific radioimmunoassay for LRF was applied to the measurement of endogenous LRF in various hypothalamic extracts. Specific antiserum was obtained by injecting LRF conjugated to human serum albumin with glutaraldehyde. Thyrotropin-releasing hormone, lysine vasopressin, oxytocin, noradrenaline, LH, FSH and cortical extracts did not appear to affect the assay, and the maximum cross-reaction observed with the LRF analogs tested was 8.5% with LRF 2-10. The best detection limit (0.4 pg/tube) was usually obtained when the labelled LRF had been purified by polyacrylamide gel electrophoresis. Within and between-assay coefficients of variation were 8.0 and 12.6% respectively (from B/Bo=20 to 80%). Synthetic LRF administered to rams by intravenous injection was readily detectable in the peripheral plasma. However, the direct measurement of plasma endogenous LRF may give misleading results due to non-specific interference by plasma factors. No endogenous LRF could be detected in plasma methanol or acetone extracts obtained from rats and rams in various physiological conditions. The inhibition curves parallel to the synthetic LRF curve were obtained by diluting the crude hypothalamic extracts of rams and rats, and a good correlation (r=0,997) with the Ramirez-McCann bioassay resulted, indicating that using radioimmunoassay to determine hypothalamic LRF content may be fruitful in studying hypothalamo-pituitary gonad interactions. The LRF content of rat and ovine hypothalami ranged from 2-8 to 20-80 ng of LRF, respectively

  8. Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y

    Science.gov (United States)

    Taksande, BG; Kotagale, NR; Nakhate, KT; Mali, PD; Kokare, DM; Hirani, K; Subhedar, NK; Chopde, CT; Ugale, RR

    2011-01-01

    BACKGROUND AND PURPOSE Agmatine, a multifaceted neurotransmitter, is abundantly expressed in the hypothalamic paraventricular nucleus (PVN). Our aim was to assess (i) the effect of agmatine on feeding behaviour and (ii) its association, if any, with neuropeptide Y (NPY). EXPERIMENTAL APPROACH Satiated rats fitted with intra-PVN cannulae were administered agmatine, alone or jointly with (i) α2-adrenoceptor agonist, clonidine, or antagonist, yohimbine; (ii) NPY, NPY Y1 receptor agonist, [Leu31, Pro34]-NPY, or antagonist, BIBP3226; or (iii) yohimbine and NPY. Cumulative food intake was monitored at different post-injection time points. Furthermore, the expression of hypothalamic NPY following i.p. treatment with agmatine, alone or in combination with yohimbine (i.p.), was evaluated by immunocytochemistry. KEY RESULTS Agmatine robustly increased feeding in a dose-dependent manner. While pretreatment with clonidine augmented, yohimbine attenuated the orexigenic response to agmatine. Similarly, NPY and [Leu31, Pro34]-NPY potentiated the agmatine-induced hyperphagia, whereas BIBP3226 inhibited it. Moreover, yohimbine attenuated the synergistic orexigenic effect induced by the combination of NPY and agmatine. Agmatine increased NPY immunoreactivity in the PVN fibres and in the cells of the hypothalamic arcuate nucleus (ARC) and this effect was prevented by pretreatment with yohimbine. NPY immunoreactivity in the fibres of the ARC, dorsomedial, ventromedial and lateral nuclei of the hypothalamus was not affected by any of the above treatments. CONCLUSIONS AND IMPLICATIONS The orexigenic effect of agmatine is coupled to increased NPY activity mediated by stimulation of α2-adrenoceptors within the PVN. This signifies the importance of agmatine or α2-adrenoceptor modulators in the development of novel therapeutic agents to treat feeding-related disorders. PMID:21564088

  9. Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits.

    Science.gov (United States)

    Maillard, Julien; Park, Soyoung; Croizier, Sophie; Vanacker, Charlotte; Cook, Joshua H; Prevot, Vincent; Tauber, Maithe; Bouret, Sebastien G

    2016-08-01

    Prader-Willi syndrome (PWS) is a genetic disorder characterized by a variety of physiological and behavioral dysregulations, including hyperphagia, a condition that can lead to life-threatening obesity. Feeding behavior is a highly complex process with multiple feedback loops that involve both peripheral and central systems. The arcuate nucleus of the hypothalamus (ARH) is critical for the regulation of homeostatic processes including feeding, and this nucleus develops during neonatal life under of the influence of both environmental and genetic factors. Although much attention has focused on the metabolic and behavioral outcomes of PWS, an understanding of its effects on the development of hypothalamic circuits remains elusive. Here, we show that mice lacking Magel2, one of the genes responsible for the etiology of PWS, display an abnormal development of ARH axonal projections. Notably, the density of anorexigenic α-melanocyte-stimulating hormone axons was reduced in adult Magel2-null mice, while the density of orexigenic agouti-related peptide fibers in the mutant mice appeared identical to that in control mice. On the basis of previous findings showing a pivotal role for metabolic hormones in hypothalamic development, we also measured leptin and ghrelin levels in Magel2-null and control neonates and found that mutant mice have normal leptin and ghrelin levels. In vitro experiments show that Magel2 directly promotes axon growth. Together, these findings suggest that a loss of Magel2 leads to the disruption of hypothalamic feeding circuits, an effect that appears to be independent of the neurodevelopmental effects of leptin and ghrelin and likely involves a direct neurotrophic effect of Magel2. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Hypothalamic expression of anorexigenic and orexigenic hormone receptors in obese females Neotomodon alstoni: effect of fasting.

    Science.gov (United States)

    Báez-Ruiz, Adrián; Luna-Moreno, Dalia; Carmona-Castro, Agustín; Cárdenas-Vázquez, René; Díaz-Muñoz, Mauricio; Carmona-Alcocer, Vania; Fuentes-Granados, Citlalli; Manuel, Miranda-Anaya

    2014-01-01

    Obesity is a world problem that requires a better understanding of its physiological and genetic basis, as well as the mechanisms by which the hypothalamus controls feeding behavior. The volcano mouse Neotomodon alstoni develops obesity in captivity when fed with regular chow diet, providing a novel model for the study of obesity. Females develop obesity more often than males; therefore, in this study, we analysed in females, in proestrous lean and obese, the differences in hypothalamus expression of receptors for leptin, ghrelin (growth hormone secretagogue receptor GHS-R), and VPAC, and correlates for plasma levels of total ghrelin. The main comparisons are between mice fed ad libitum and mice after 24 hours of fasting. Mice above 65 g body weight were considered obese, based on behavioral and physiological parameters such as food intake, plasma free fatty acids, and glucose tolerance. Hypothalamic tissue from obese and lean mice was analysed by western blot. Our results indicate that after ad libitum food access, obese mice show no significant differences in hypothalamic leptin receptors, but a significant increase of 60% in the GHS-R, and a nearly 62% decrease in VPAC2 was noted. After a 24-hour fast, plasma ghrelin increased nearly two fold in both lean and obese mice; increases of hypothalamic leptin receptors and GHS-R were also noted, while VPAC2 did not change significantly; levels of plasma free fatty acids were 50% less after fasting in obese than in lean animals. Our results indicate that in obese N. alstoni mice, the levels of orexigenic receptors in the hypothalamus correlate with overfeeding, and the fact that lean and obese females respond in different ways to a metabolic demand such as a 24-hour fast.

  11. Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice

    Science.gov (United States)

    Zhang, Rong; Asai, Masato; Mahoney, Carrie E; Joachim, Maria; Shen, Yuan; Gunner, Georgia; Majzoub, Joseph A

    2016-01-01

    A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, while extra-hypothalamic CRH plays a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma ACTH, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open field, elevated plus maze, holeboard, light-dark box, and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus, and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation. PMID:27595593

  12. Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward.

    Science.gov (United States)

    Kelley, Ann E; Baldo, Brian A; Pratt, Wayne E; Will, Matthew J

    2005-12-15

    Work over the past decade has supported the idea that discrete aspects of appetitive motivation are differentially mediated by separate but interacting neurochemical systems within the nucleus accumbens (Acb). We review herein a series of studies in rats comparing the effects of manipulating Acb amino acid, opioid, acetylcholine, and dopamine systems on tests of free-feeding and food-reinforced operant responding. Results from our laboratory and in the literature support three general conclusions: (1) GABA output neurons localized exclusively within the Acb shell directly influence hypothalamic effector mechanisms for feeding motor patterns, but do not participate in the execution of more complex food-seeking strategies; (2) enkephalinergic neurons distributed throughout the Acb and caudate-putamen mediate the hedonic impact of palatable (high sugar/fat) foods, and these neurons are under modulatory control by striatal cholinergic interneurons; and (3) dopamine transmission in the Acb governs general motoric and arousal processes related to response selection and invigoration, as well as motor learning-related plasticity. These dissociations may reflect the manner in which these neurochemical systems differentially access pallido-thalamo-cortical loops reaching the voluntary motor system (in the case of opioids and dopamine), versus more restricted efferent connections to hypothalamic motor/autonomic control columns (in the case of Acb shell GABA and glutamate systems). Moreover, we hypothesize that while these systems work in tandem to coordinate the anticipatory and consummatory phases of feeding with hypothalamic energy-sensing substrates, the striatal opioid network evolved a specialized capacity to promote overeating of energy-dense foods beyond acute homeostatic needs, to ensure an energy reserve for potential future famine.

  13. Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, A D; Stomati, M; Bersi, C; Luisi, S; Fedalti, M; Santuz, M; Esposito, G; Petraglia, F; Genazzani, A R

    2000-09-01

    Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.

  14. Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

    2001-09-01

    To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

  15. Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L

    2006-04-01

    The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

  16. Fetal alcohol programming of hypothalamic proopiomelanocortin system by epigenetic mechanisms and later life vulnerability to stress.

    Science.gov (United States)

    Bekdash, Rola; Zhang, Changqing; Sarkar, Dipak

    2014-09-01

    Hypothalamic proopiomelanocortin (POMC) neurons, one of the major regulators of the hypothalamic-pituitary-adrenal (HPA) axis, immune functions, and energy homeostasis, are vulnerable to the adverse effects of fetal alcohol exposure (FAE). These effects are manifested in POMC neurons by a decrease in Pomc gene expression, a decrement in the levels of its derived peptide β-endorphin and a dysregulation of the stress response in the adult offspring. The HPA axis is a major neuroendocrine system with pivotal physiological functions and mode of regulation. This system has been shown to be perturbed by prenatal alcohol exposure. It has been demonstrated that the perturbation of the HPA axis by FAE is long-lasting and is linked to molecular, neurophysiological, and behavioral changes in exposed individuals. Recently, we showed that the dysregulation of the POMC system function by FAE is induced by epigenetic mechanisms such as hypermethylation of Pomc gene promoter and an alteration in histone marks in POMC neurons. This developmental programming of the POMC system by FAE altered the transcriptome in POMC neurons and induced a hyperresponse to stress in adulthood. These long-lasting epigenetic changes influenced subsequent generations via the male germline. We also demonstrated that the epigenetic programming of the POMC system by FAE was reversed in adulthood with the application of the inhibitors of DNA methylation or histone modifications. Thus, prenatal environmental influences, such as alcohol exposure, could epigenetically modulate POMC neuronal circuits and function to shape adult behavioral patterns. Identifying specific epigenetic factors in hypothalamic POMC neurons that are modulated by fetal alcohol and target Pomc gene could be potentially useful for the development of new therapeutic approaches to treat stress-related diseases in patients with fetal alcohol spectrum disorders. Copyright © 2014 by the Research Society on Alcoholism.

  17. Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation therapy: a retrospective study

    International Nuclear Information System (INIS)

    Lam, K.S.; Ho, J.H.; Lee, A.W.; Tse, V.K.; Chan, P.K.; Wang, C.; Ma, J.T.; Yeung, R.T.

    1987-01-01

    Endocrine assessment was performed in 32 relapse-free southern Chinese patients 5-17 years following radiation therapy (RT) alone for early nasopharyngeal carcinoma (NPC). Initial screening was done using questionnaires emphasizing impaired sexual function and menstrual disturbance plus measurement of serum levels of thyroxine, free thyroxine index, thyrotropic hormone, prolactin, and additionally testosterone for males only. Those showing abnormalities were subjected to detailed pituitary function tests. Hypothalamic-pituitary dysfunction was found in 7 female patients and only 1 male patient. A delayed TSH response to thyrotropin releasing hormone suggesting a hypothalamic disorder was seen in 6 of the affected female patients, and hyperprolactinaemia in also 6. None of the patients had evidence of diabetes insipidus. Hypopituitarism became symptomatic 2-5 years after RT with a mean latent interval of 3.8 years. A practical protocol for regular endocrine assessment for NPC patients after RT has been proposed. Multiple linear regression analysis of the radiotherapeutic data from the 11 female patients indicates that the likelihood of late occurrence of symptomatic hypothalamic-pituitary dysfunction following RT is dependent on the TDF of the target dose to the nasopharyngeal region and the height of the upper margin of the opposed lateral facial fields above the diaphragma sellae (coefficient of multiple correlation = 0.9025). Except when the sphenoid sinus or the middle cranial fossa is involved, it is advisable to set the height of the upper margin of the lateral facial field at a level no higher than the diaphragma sellae. The hypothalamus and possibly the pituitary stalk as well may sustain permanent damage by doses of radiation within the conventional radiotherapeutic range for carcinomas

  18. Hypothalamic FTO is associated with the regulation of energy intake not feeding reward

    Directory of Open Access Journals (Sweden)

    Radomska Katarzyna J

    2009-10-01

    Full Text Available Abstract Background Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal. Results Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin. Conclusion We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.

  19. Hypothalamic neuronal toll-like receptor 2 protects against age-induced obesity

    OpenAIRE

    Shechter, Ravid; London, Anat; Kuperman, Yael; Ronen, Ayal; Rolls, Asya; Chen, Alon; Schwartz, Michal

    2013-01-01

    Toll-like receptors (TLRs) are traditionally associated with immune-mediated host defense. Here, we ascribe a novel extra-immune, hypothalamic-associated function to TLR2, a TLR-family member known to recognize lipid components, in the protection against obesity. We found that TLR2-deficient mice exhibited mature-onset obesity and susceptibility to high-fat diet (HFD)-induced weight gain, via modulation of food intake. Age-related obesity was still evident in chimeric mice, carrying comparabl...

  20. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

    Directory of Open Access Journals (Sweden)

    Jereme G. Spiers

    2015-01-01

    Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

  1. [The hypothalamic syndrome in childhood (its epidemiological and clinico-electrophysiological aspects)].

    Science.gov (United States)

    Solov'eva, A D; Vorob'eva, O V; Loseva, M M; Khaspekova, N B; Fedorova, V I; Musaeva, Z A; Filatova, E G

    1994-01-01

    The epidemiological survey covered 2000 city schoolchildren. They ranged in age from 7 to 15 years. Hypothalamic deficiency (HD) was detected in 5% of the examinees. Clinical and physiological findings on HD children are provided. They were found to have the history of hereditary or natal damage evidencing the acquired nature of the disease. Special emphasis is placed on HD manifestations in prepubertal and pubertal age. The authors show defective regulation of nonspecific brain systems in the form of predominant activation of the septohippocampal system and relative insufficiency of the brain stem mesencephalic reticular formation. Activation of cerebral ergotropic vegetative mechanisms combines with peripheral vegetative failure (sympathetic and parasympathetic), probably, of congenital origin.

  2. Supraependymal cells of hypothalamic third ventricle: identification as resident phagocytes of the brain.

    Science.gov (United States)

    Bleier, R; Albrecht, R; Cruce, J A

    1975-07-25

    Cells lying on the ventricular surface of the hypothalamic ependyma of the tegu lizard exhibit the pseudopodial and flaplike processes characteristic of macrophages found elsewhere. Since they ingest latex beads, they may be considered a resident phagocytic system of the brain. The importance of ependyma and ventricular phagocytes as a first line of defense against viral invasion of the brain, as well as their role in the pathogenesis of certain virus-related diseases, is suggested by a number of experimental and clinical observations.

  3. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

    Science.gov (United States)

    Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

    2015-09-04

    Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

  4. Involvement of CART in estradiol-induced anorexia.

    Science.gov (United States)

    Dandekar, Manoj P; Nakhate, Kartik T; Kokare, Dadasaheb M; Subhedar, Nishikant K

    2012-01-18

    Since estradiol exercises inhibitory effect on food intake, we wanted to find out if this influence of estradiol is mediated by cocaine- and amphetamine-regulated transcript peptide (CART), a well established anorectic agent in the brain. Ovariectomized (OVX) rats, replaced with estradiol to produce estrous-phase like conditions, showed a significant decrease in food intake as compared with that in OVX controls. Intracerebroventricular (icv) administration of CART (0.5-1 μg/rat) to OVX rats, resulted in a dose-dependent reduction in the food intake. The lower dose (0.25 μg) had no effect, and was considered subeffective. In estradiol replaced OVX rats, CART at subeffective dose, further reduced food intake. However, CART failed to reduce food intake in estradiol replaced OVX rats pretreated with anti-estrogenic agent tamoxifen (3 mg/kg, subcutaneous). Administration of CART antibody (1:500 dilution/rat, i.c.v.) significantly attenuated estradiol-induced anorexia in the OVX rats. While estradiol replacement significantly increased CART-immunoreactivity in the cells/fibers of paraventricular nucleus (PVN) of OVX rats, fibers in the anteroventral periventricular nucleus (AVPV), and cells/fibers in the arcuate nucleus (ARC) showed considerable reduction. These changes were attenuated following concurrent injection of tamoxifen to the estradiol replaced OVX rats. However, CART-immunoreactive cells/fibers in the periventricular area did not respond to any of the treatments. We suggest that estradiol treatment might influence the hypothalamic CART system in a site specific manner. While increased CART activity in the PVN might produce anorexia, reduction of CART in ARC and AVPV might represent a compensatory homeostatic response. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Short-Term High-Fat Diet Increases Leptin Activation of CART Neurons and Advances Puberty in Female Mice.

    Science.gov (United States)

    Venancio, Jade Cabestre; Margatho, Lisandra Oliveira; Rorato, Rodrigo; Rosales, Roberta Ribeiro Costa; Debarba, Lucas Kniess; Coletti, Ricardo; Antunes-Rodrigues, Jose; Elias, Carol F; Elias, Lucila Leico K

    2017-11-01

    Leptin is a permissive factor for puberty initiation, participating as a metabolic cue in the activation of the kisspeptin (Kiss1)-gonadotropin-releasing hormone neuronal circuitry; however, it has no direct effect on Kiss1 neurons. Leptin acts on hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons, participating in the regulation of energy homeostasis. We investigated the influence of a short-term high-fat diet (HFD) on the effect of leptin on puberty timing. Kiss1-hrGFP female mice received a HFD or regular diet (RD) after weaning at postnatal day (PN)21 and were studied at PN28 and PN32. The HFD increased body weight and plasma leptin concentrations and decreased the age at vaginal opening (HFD, 32 ± 0.53 days; RD, 38 ± 0.67 days). Similar colocalization of neurokinin B and dynorphin in Kiss1-hrGFP neurons of the arcuate nucleus (ARC) was observed between the HFD and RD groups. The HFD increased CART expression in the ARC and Kiss1 messenger RNA expression in the anteroventral periventricular (AVPV)/anterior periventricular (Pe). The HFD also increased the number of ARC CART neurons expressing leptin-induced phosphorylated STAT3 (signal transducer and activator of transcription 3) at PN32. Close apposition of CART fibers to Kiss1-hrGFP neurons was observed in the ARC of both RD- and HFD-fed mice. In conclusion, these data reinforce the notion that a HFD increases kisspeptin expression in the AVPV/Pe and advances puberty initiation. Furthermore, we have demonstrated that the HFD-induced earlier puberty is associated with an increase in CART expression in the ARC. Therefore, these data indicate that CART neurons in the ARC can mediate the effect of leptin on Kiss1 neurons in early puberty induced by a HFD. Copyright © 2017 Endocrine Society.

  6. Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study.

    Science.gov (United States)

    Steele, C A; Powell, J L; Kemp, G J; Halford, J C G; Wilding, J P; Harrold, J A; Kumar, S V D; Cuthbertson, D J; Cross, A A; Javadpour, M; MacFarlane, I A; Stancak, A A; Daousi, C

    2015-09-01

    Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.

  7. AgRP and NPY Expression in the Human Hypothalamic Infundibular Nucleus Correlate with Body Mass Index, Whereas Changes in alpha MSH Are Related to Type 2 Diabetes

    NARCIS (Netherlands)

    Alkemade, Anneke; Yi, Chun-Xia; Pei, Lei; Harakalova, Magdalena; Swaab, Dick F.; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

    2012-01-01

    Context: Rodent data show that altered hypothalamic signaling contributes to the development of obesity and insulin resistance. Objective: To determine differences in hypothalamic expression levels of neuropeptide Y (NPY), agouti-related peptide (AgRP), and alpha MSH in the infundibular nucleus, the

  8. Disabling amnestic syndrome following stereotactic laser ablation of a hypothalamic hamartoma in a patient with a prior temporal lobectomy

    Directory of Open Access Journals (Sweden)

    Sarah Zubkov

    2015-01-01

    Full Text Available A 19-year-old man with cortical dysplasia and intractable focal seizures underwent a right temporal lobectomy. A hypothalamic hamartoma was subsequently recognized, and he then underwent MRI-guided stereotactic laser ablation. Unfortunately, he sustained damage to the bilateral medial mammillary bodies and suffered significant memory loss. We review laser ablation therapy for hypothalamic hamartomas and the anatomy of the memory network. We postulate that his persistent memory disorder resulted from a combination of the right temporal lobectomy and injury to the bilateral medial mammillary bodies.

  9. Hypothalamic amenorrhea. The effects of environmental stresses on the reproductive system: a central effect of the central nervous system.

    Science.gov (United States)

    Warren, M P; Fried, J L

    2001-09-01

    Although the treatment of anovulation has become significantly more specialized and complex in the centuries since Hippocrates, a complete understanding of the causes and mechanisms of hypothalamic amenorrhea has not been achieved. Even the best research on hypothalamic amenorrhea is plagued by the lack of longitudinal studies, the use of different exercise models, the difficulty of controlling for caloric intake, and the fact that genetics may have a role in the disorder. Continuing research on metabolic rate, leptin, and other factors will ultimately answer many of the outstanding questions and will help to create better tools for treating this disorder.

  10. Electrophysiology of Hypothalamic Magnocellular Neurons In vitro: A Rhythmic Drive in Organotypic Cultures and Acute Slices.

    Science.gov (United States)

    Israel, Jean-Marc; Oliet, Stéphane H; Ciofi, Philippe

    2016-01-01

    Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains.

  11. Electrophysiology of hypothalamic magnocellular neurons in vitro: a rhythmic drive in organotypic cultures and acute slices

    Directory of Open Access Journals (Sweden)

    Jean-Marc eIsrael

    2016-03-01

    Full Text Available Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains.

  12. An 11-month-old girl with central precocious puberty caused by hypothalamic hamartoma

    Directory of Open Access Journals (Sweden)

    Da Young Yoon

    2016-12-01

    Full Text Available Central precocious puberty (CPP is caused by premature activation of the hypothalamic-gonadal axis, and must be treated adequately. In particular, CPP that occurs at a relatively young age or in boys is likely to be caused by an organic lesion. Hypothalamic hamartoma (HH is the most common organic cause of CPP. The present case report describes an 11-month-old female infant who presented with vaginal bleeding and rapidly progressive secondary sex characteristics from the age of 6 months. She was diagnosed with CPP following the detection of HH via magnetic resonance imaging. The infant girl was successfully treated with gonadotropin-releasing hormone agonist. After 6 months, her breast had regressed and clinical and radiological follow-up demonstrated stable findings with no evidence of tumor growth or secondary sexual characteristics until the fourth year after the initiation of treatment. This patient is the one of the youngest infants presenting with CPP and HH in Korea; treatment was successful over a relatively long follow-up period.

  13. The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

    2016-01-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

  14. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  15. On the acoustic wave sensor response to immortalized hypothalamic neurons at the device-liquid interface

    Directory of Open Access Journals (Sweden)

    Shilin Cheung

    2016-12-01

    Full Text Available The response of a thickness shear mode biosensor to immortalized murine hypothalamic neurons (mHypoE-38 and -46 cells under a variety of conditions and stimuli is discussed. Cellular studies which lead to the production of detectable neuronal responses include neuronal deposition, adhesion and proliferation, alteration in the extent of specific cell-surface interactions, actin filament and microtubule cytoskeletal disruptions, effects of cell depolarization, inhibition of the Na+-K+ pump via ouabain, effects of neuronal synchronization and the effects ligand-receptor interaction (glucagon. In the presence of cells, fs shifts are largely influenced by the damping of the TSM resonator. The formation of cell-surface interactions and hence the increase in coupling and acoustic energy dissipation can be modeled as an additional resistor in the BVD model. Further sensor and cellular changes can be obtained by negating the effects of damping from fs via the use of Rm and θmax. Keywords: Acoustic wave sensor, Hypothalamic neurons, Neuron cell-surface interaction

  16. The orexin neuropeptide system: Physical activity and hypothalamic function throughout the aging process.

    Directory of Open Access Journals (Sweden)

    Anastasia N Zink

    2014-11-01

    Full Text Available There is a rising medical need for novel therapeutic targets of physical activity. Physical activity spans from spontaneous, low intensity movements to voluntary, high-intensity exercise. Regulation of spontaneous and voluntary movement is distributed over many brain areas and neural substrates, but the specific cellular and molecular mechanisms responsible for mediating overall activity levels are not well understood. The hypothalamus plays a central role in the control of physical activity, which is executed through coordination of multiple signaling systems, including the orexin neuropeptides. Orexin producing neurons integrate physiological and metabolic information to coordinate multiple behavioral states and modulate physical activity in response to the environment. This review is organized around three questions: (1 How do orexin peptides modulate physical activity? (2 What are the effects of aging and lifestyle choices on physical activity? (3 What are the effects of aging on hypothalamic function and the orexin peptides? Discussion of these questions will provide a summary of the current state of knowledge regarding hypothalamic orexin regulation of physical activity during aging and provide a platform on which to develop improved clinical outcomes in age-associated obesity and metabolic syndromes.

  17. Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome.

    Science.gov (United States)

    Baskind, N Ellissa; Balen, Adam H

    2016-11-01

    Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous disorder linked with disturbances of reproductive, endocrine and metabolic function. The definition and aetiological hypotheses of PCOS are continually developing to incorporate evolving evidence of the syndrome, which appears to be both multifactorial and polygenic. The pathophysiology of PCOS encompasses inherent ovarian dysfunction that is strongly influenced by external factors including the hypothalamic-pituitary axis and hyperinsulinaemia. Neuroendocrine abnormalities including increased gonadotrophin-releasing hormone (GnRH) pulse frequency with consequent hypersecretion of luteinising hormone (LH) affects ovarian androgen synthesis, folliculogenesis and oocyte development. Disturbed ovarian-pituitary and hypothalamic feedback accentuates the gonadotrophin abnormalities, and there is emerging evidence putatively implicating dysfunction of the Kiss 1 system. Within the follicle subunit itself, there are intra-ovarian paracrine modulators, cytokines and growth factors, which appear to play a role. Adrenally derived androgens may also contribute to the pathogenesis of PCOS, but their role is less defined. Copyright © 2016. Published by Elsevier Ltd.

  18. Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

    Science.gov (United States)

    Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

    2018-04-16

    The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018. Published by Elsevier B.V.

  19. Astrocytes Modulate a Postsynaptic NMDA–GABAA-Receptor Crosstalk in Hypothalamic Neurosecretory Neurons

    Science.gov (United States)

    Potapenko, Evgeniy S.; Biancardi, Vinicia C.; Zhou, Yiqiang

    2013-01-01

    A dynamic balance between the excitatory and inhibitory neurotransmitters glutamate and GABA is critical for maintaining proper neuronal activity in the brain. This balance is partly achieved via presynaptic interactions between glutamatergic and GABAAergic synapses converging into the same targets. Here, we show that in hypothalamic magnocellular neurosecretory neurons (MNCs), a direct crosstalk between postsynaptic NMDA receptors (NMDARs) and GABAA receptors (GABAARs) contributes to the excitatory/inhibitory balance in this system. We found that activation of NMDARs by endogenous glutamate levels controlled by astrocyte glutamate transporters, evokes a transient and reversible potentiation of postsynaptic GABAARs. This inter-receptor crosstalk is calcium-dependent and involves a kinase-dependent phosphorylation mechanism, but does not require nitric oxide as an intermediary signal. Finally, we found the NMDAR–GABAAR crosstalk to be blunted in rats with heart failure, a pathological condition in which the hypothalamic glutamate–GABA balance is tipped toward an excitatory predominance. Together, our findings support a novel form of glutamate–GABA interactions in MNCs, which involves crosstalk between NMDA and GABAA postsynaptic receptors, whose strength is controlled by the activity of local astrocytes. We propose this inter-receptor crosstalk to act as a compensatory, counterbalancing mechanism to dampen glutamate-mediated overexcitation. Finally, we propose that an uncoupling between NMDARs and GABAARs may contribute to exacerbated neuronal activity and, consequently, sympathohumoral activation in such disease conditions as heart failure. PMID:23303942

  20. Malathion exposure modulates hypothalamic gene expression and induces dyslipedemia in Wistar rats.

    Science.gov (United States)

    Rezg, Raja; Mornagui, Bessem; Benahmed, Malika; Chouchane, Sonia Gharsalla; Belhajhmida, Nadia; Abdeladhim, Maha; Kamoun, Abdelaziz; El-fazaa, Saloua; Gharbi, Najoua

    2010-06-01

    Exposure to organophosphate (OP) pesticides is virtually ubiquitous. These inevitable agents are neurotoxicants, but recent evidence also points to lasting effects on carbohydrate metabolism. The aim of this study was to investigate the effects of 32 repeated treatment days with malathion, an OP insecticide, on some molecular and metabolic parameters. Malathion at 100 mg/kg was administered by gavage in Wistar rats. Results of this study indicate a significant decrease in hypothalamic corticotropin-releasing hormone mRNA, of malathion-treated rats. This result, in accordance with that of diabetic type 2 rat model, may be due to very potent negative feedback effects of glucocorticoids on hypothalamo-pituitary-adrenal (HPA) axis activity. In addition, we have recorded a significant increase in hypothalamic inducible NO synthase mRNA which probably enhances the negative feedback. These alterations are accompanied with hypertriglyceridemia that may be a favourable condition to insulin resistance. Thus, results of the present study suggest that malathion can be considered as an important risk factor in the development of diabetes type 2, which prevalence increased substantially in our country and around the world. Clearly, we need to focus further research on the specific incidences of hazardous food chemical contaminant that might be contributing to epidemic health perspectives. Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.

  1. Hypothalamic PGC-1α Protects Against High-Fat Diet Exposure by Regulating ERα

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    Eugenia Morselli

    2014-10-01

    Full Text Available High-fat diets (HFDs lead to obesity and inflammation in the central nervous system (CNS. Estrogens and estrogen receptor α (ERα protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

  2. Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα.

    Science.gov (United States)

    Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P; Li, Dan L; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F; Tschöp, Matthias H; Clegg, Deborah J

    2014-10-23

    High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor α (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

  3. Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome.

    Science.gov (United States)

    Armario, Antonio

    2010-07-01

    Addictive drugs (opiates, ethanol, cannabinoids (CBs), nicotine, cocaine, amphetamines) induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, with the subsequent release of adrenocorticotropic hormone and glucocorticoids. The sequence of events leading to HPA activation appears to start within the brain, suggesting that activation is not secondary to peripheral homeostatic alterations. The precise neurochemical mechanisms and brain pathways involved are markedly dependent on the particular drug, although it is assumed that information eventually converges into the hypothalamic paraventricular nucleus (PVN). Whereas some drugs may act on the hypothalamus or directly within PVN neurons (i.e. ethanol), others exert their primary action outside the PVN (i.e. CBs, nicotine, cocaine). Corticotropin-releasing hormone (CRH) has a critical role in most cases, but the changes in c-fos and CRH gene expression in the PVN also reveal differences among drugs. More studies are needed to understand how addictive drugs act on this important neuroendocrine system and their functional consequences. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Optogenetic Activation of a Lateral Hypothalamic-Ventral Tegmental Drive-Reward Pathway.

    Science.gov (United States)

    Gigante, Eduardo D; Benaliouad, Faiza; Zamora-Olivencia, Veronica; Wise, Roy A

    2016-01-01

    Electrical stimulation of the lateral hypothalamus can motivate feeding or can serve as a reward in its own right. It remains unclear whether the same or independent but anatomically overlapping circuitries mediate the two effects. Electrical stimulation findings implicate medial forebrain bundle (MFB) fibers of passage in both effects, and optogenetic studies confirm a contribution from fibers originating in the lateral hypothalamic area and projecting to or through the ventral tegmental area. Here we report that optogenetic activation of ventral tegmental fibers from cells of origin in more anterior or posterior portions of the MFB failed to induce either reward or feeding. The feeding and reward induced by optogenetic activation of fibers from the lateral hypothalamic cells of origin were influenced similarly by variations in stimulation pulse width and pulse frequency, consistent with the hypothesis of a common substrate for the two effects. There were, however, several cases where feeding but not self-stimulation or self-stimulation but not feeding were induced, consistent with the hypothesis that distinct but anatomically overlapping systems mediate the two effects. Thus while optogenetic stimulation provides a more selective tool for characterizing the mechanisms of stimulation-induced feeding and reward, it does not yet resolve the question of common or independent substrates.

  5. Assessment of endocrine disorders of the hypothalamic-pituitary axis by nuclear medicine techniques

    International Nuclear Information System (INIS)

    Schmidt, M.; Theissen, P.; Dietlein, M.; Schicha, H.; Jackenhoevel, F.; Krone, W.

    2002-01-01

    The following article reviews nuclear medicine techniques which can be used for assessment of endocrine disorders of the hypothalamic-pituitary axis. For planar and SPECT imaging somatostatin-receptor- and dopamine-D2-receptor-scintigraphy are the most widely distributed techniques. These nuclear medicine techniques may be indicated in selected cases to answer differential diagnostic problems. They can be helpful to search for presence and localization of receptor positive tissue. Furthermore they can detect metastasis in the rare cases of a pituitary carcinoma. Scintigraphy with Gallium-67 is suitable for further diagnostic evaluation in suspected hypophysitis. Other SPECT radiopharmaca do not have relevant clinical significance. F-18-FDG as PET radiopharmacon is not ideal because obvious pituitary adenomas could not be visualized. Other PET radiopharmaca including C-11-methionine, C-11-tyrosine, F-18-fluoroethylspiperone, C-11-methylspiperone, and C-11-raclopride are available in specialized centers only. Overall indications for nuclear medicine in studies for the assessment of endocrine disorders of the hypothalamic-pituitary-axis are rare. Original studies often report only about a small number of patients. According to the authors' opinion the relevance of nuclear medicine in studies of clinically important endocrinologic fields, e. g. localization of small ACTH-producing pituitary adenomas, tumor localization in ectopic ACTH syndrome, localization of recurrent pituitary tissue, assessment of small incidentalomas, can not be definitely given yet. (orig.) [de

  6. Effects of chronic restraint stress on body weight, food intake, and hypothalamic gene expressions in mice.

    Science.gov (United States)

    Jeong, Joo Yeon; Lee, Dong Hoon; Kang, Sang Soo

    2013-12-01

    Stress affects body weight and food intake, but the underlying mechanisms are not well understood. We evaluated the changes in body weight and food intake of ICR male mice subjected to daily 2 hours restraint stress for 15 days. Hypothalamic gene expression profiling was analyzed by cDNA microarray. Daily body weight and food intake measurements revealed that both parameters decreased rapidly after initiating daily restraint stress. Body weights of stressed mice then remained significantly lower than the control body weights, even though food intake slowly recovered to 90% of the control intake at the end of the experiment. cDNA microarray analysis revealed that chronic restraint stress affects the expression of hypothalamic genes possibly related to body weight control. Since decreases of daily food intake and body weight were remarkable in days 1 to 4 of restraint, we examined the expression of food intake-related genes in the hypothalamus. During these periods, the expressions of ghrelin and pro-opiomelanocortin mRNA were significantly changed in mice undergoing restraint stress. Moreover, daily serum corticosterone levels gradually increased, while leptin levels significantly decreased. The present study demonstrates that restraint stress affects body weight and food intake by initially modifying canonical food intake-related genes and then later modifying other genes involved in energy metabolism. These genetic changes appear to be mediated, at least in part, by corticosterone.

  7. Neurogenin 3 Mediates Sex Chromosome Effects on the Generation of Sex Differences in Hypothalamic Neuronal Development

    Directory of Open Access Journals (Sweden)

    Maria Julia Scerbo

    2014-07-01

    Full Text Available The organizational action of testosterone during critical periods of development is the cause of numerous sex differences in the brain. However, sex differences in neuritogenesis have been detected in primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal testis. In the present study we assessed the hypothesis of that cell-autonomous action of sex chromosomes can differentially regulate the expression of the neuritogenic gene neurogenin 3 (Ngn3 in male and female hypothalamic neurons, generating sex differences in neuronal development. Neuronal cultures were prepared from male and female E14 mouse hypothalami, before the fetal peak of testosterone. Female neurons showed enhanced neuritogenesis and higher expression of Ngn3 than male neurons. The silencing of Ngn3 abolished sex differences in neuritogenesis, decreasing the differentiation of female neurons. The sex difference in Ngn3 expression was determined by sex chromosomes, as demonstrated using the four core genotypes mouse model, in which a spontaneous deletion of the testis-determining gene Sry from the Y chromosome was combined with the insertion of the Sry gene onto an autosome. In addition, the expression of Ngn3, which is also known to mediate the neuritogenic actions of estradiol, was increased in the cultures treated with the hormone, but only in those from male embryos. Furthermore, the hormone reversed the sex differences in neuritogenesis promoting the differentiation of male neurons. These findings indicate that Ngn3 mediates both cell-autonomous actions of sex chromosomes and hormonal effects on neuritogenesis.

  8. Psychopathological traits of adolescents with functional hypothalamic amenorrhea: a comparison with anorexia nervosa.

    Science.gov (United States)

    Bomba, Monica; Corbetta, Fabiola; Bonini, Luisa; Gambera, Alessandro; Tremolizzo, Lucio; Neri, Francesca; Nacinovich, Renata

    2014-03-01

    Functional hypothalamic amenorrhea (FHA) is a form of anovulation, due to the suppression of hypothalamic-pituitary-ovarian axis, not related to identifiable organic causes. Like adolescents with anorexia nervosa (AN), subjects with FHA show dysfunctional attitudes, low self-esteem, depressive mood, anxiety and inability to cope with daily stress. The aim of the study is to examine similarities and differences between FHA and AN in terms of clinical profiles and psychological variables. 21 adolescents with FHA, 21 adolescents with anorexia nervosa, and 21 healthy adolescents were included in the study. All the teenagers completed a battery of self-administered psychological tests for the detection of behaviors and symptoms attributable to the presence of an eating disorder (EDI-2), depression (CDI), and alexithymia (TAS-20). Different from healthy controls, subjects with FHA and with AN shared common psychopathological aspects, such as maturity issues, social insecurity and introversion, a tendency to depression, excessive concerns with dieting, and fear of gaining weight. Nevertheless, adolescents with AN presented a more profound psychopathological disorder as observed at test comparisons with subjects with FHA. Results show a clinical spectrum that includes AN and FHA and suggest the necessity to treat FHA with a multidisciplinary approach for both organic and psychological aspects.

  9. Functional hypothalamic amenorrhea is associated with elevated ghrelin and disordered eating.

    Science.gov (United States)

    Schneider, Lisa F; Warren, Michelle P

    2006-12-01

    To determine whether ghrelin, an orexigen released by the stomach, is elevated in women with hypothalamic amenorrhea who are of normal weight and whether this is associated with abnormal eating behaviors. Controlled clinical study. Healthy volunteers in an academic research environment. Twenty-seven women with functional hypothalamic amenorrhea (FHA) and 42 normally menstruating women. None. Ghrelin and eating behavior. Ghrelin was significantly elevated in FHA (648.4 +/- 92.0 pg/mL vs. controls 596.7 +/- 79.0 pg/mL), while leptin, although lower, was not significantly so (FHA 5.4 +/- 2.8 ng/mL vs. controls 6.4 +/- 3 ng/mL). Eating Attitudes Test (EAT) scores were also significantly elevated in FHA (15.3 +/- 10.6 vs. controls 10.3 +/- 8.4), particularly on the subscale that measured bulimic behaviors. However, FHA patients consumed significantly more kilocalories (1,930 kcal/day vs. 1,588 kcal/day). High ghrelin in women with FHA may be linked to abnormal dietary behaviors, as reflected in high EAT scores yet characterized by normal caloric intake. Ghrelin may act as a restraining metabolic signal preventing a return to cyclicity in women with both disordered eating and FHA, prolonging amenorrhea when leptin has returned to normal.

  10. Endocrine profiles and neuropsychologic correlates of functional hypothalamic amenorrhea in adolescents.

    Science.gov (United States)

    Bomba, Monica; Gambera, Alessandro; Bonini, Luisa; Peroni, Maria; Neri, Francesca; Scagliola, Pasquale; Nacinovich, Renata

    2007-04-01

    To determine trigger factors and neuropsychologic correlates of functional hypothalamic amenorrhea (FHA) in adolescence and to evaluate the correlations with the endocrine-metabolic profile. Cross-sectional comparison of adolescents with FHA and eumenorrheic controls Academic medical institution Twenty adolescent girls with FHA (aged <18 years) and 20 normal cycling girls All subjects underwent endocrine-gynecologic (hormone) and neuropsychiatric (tests and interview) investigations. A separate semistructured interview was also used to investigate parents. Gonadotropins, leptin, prolactin, androgens, estrogens, cortisol, carrier proteins (SHBG, insulin-like growth factor-binding protein 1), and metabolic parameters (insulin, insulin-like growth factor 1, thyroid hormones) were assayed in FHA and control subjects. All girls were evaluated using a test for depression, a test for disordered eating, and a psychodynamic semistructured interview. Adolescents with FHA showed a particular susceptibility to common life events, restrictive disordered eating, depressive traits, and psychosomatic disorders. The endocrine-metabolic profile was strictly correlated to the severity of the psychopathology. Functional hypothalamic amenorrhea in adolescence is due to a particular neuropsychologic vulnerability to stress, probably related to familial relationship styles, expressed by a proportional endocrine impairment.

  11. Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea.

    Science.gov (United States)

    Drakopoulos, Panagiotis; Casarosa, Elena; Bucci, Fiorella; Piccinino, Manuela; Wenger, Jean-Marie; Nappi, Rossella Elena; Polyzos, Nicholas; Genazzani, Andrea Riccardo; Pluchino, Nicola

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. BDNF plasma levels are significantly lower in amenorrheic women (p 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA. © 2015 S. Karger AG, Basel.

  12. New protocol of clomiphene citrate treatment in women with hypothalamic amenorrhea.

    Science.gov (United States)

    Borges, Lavinia Estrela; Morgante, Giuseppe; Musacchio, Maria Concetta; Petraglia, Felice; De Leo, Vincenzo

    2007-06-01

    To determine if a new protocol of administration of clomiphene citrate (CC) is effective in menstrual cycle recovery in women with hypothalamic secondary amenorrhea. This was an open-label study. Patients comprised a group of eight women with secondary amenorrhea. Interventions. An oral preparation containing CC (50 mg/day) was administered for 5 days followed by a double dose (100 mg/day) for another 5 days, initiated on day 3 after estrogen/progestogen-induced withdrawal bleeding. If ovulation and vaginal bleeding occurred, treatment continued in the two next months with 100 mg/day from day 3 to day 7 day of the cycle. Cycle control was evaluated at each visit, when patients recorded bleeding patterns and tablet intake. Data on the intensity and duration of bleeding were collected. Six patients responded to the first cycle of CC administration, resuming normal menstrual cycles. The other two patients failed to menstruate after the first 10 days of treatment with CC and repeated the same protocol. After the second administration, these two women also had normal menstrual bleeding. The present data show that this new protocol of CC treatment may be useful to restore normal menstrual cycles in young women with hypothalamic amenorrhea.

  13. Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior.

    Science.gov (United States)

    Reis, Wagner L; Yi, Chun-Xia; Gao, Yuanqing; Tschöp, Mathias H; Stern, Javier E

    2015-04-01

    Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior.

  14. Hypothalamic mTOR pathway mediates thyroid hormone-induced hyperphagia in hyperthyroidism.

    Science.gov (United States)

    Varela, Luis; Martínez-Sánchez, Noelia; Gallego, Rosalía; Vázquez, María J; Roa, Juan; Gándara, Marina; Schoenmakers, Erik; Nogueiras, Rubén; Chatterjee, Krishna; Tena-Sempere, Manuel; Diéguez, Carlos; López, Miguel

    2012-06-01

    Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid rats exhibit marked up-regulation of the hypothalamic mammalian target of rapamycin (mTOR) signalling pathway associated with increased mRNA levels of agouti-related protein (AgRP) and neuropeptide Y (NPY), and decreased mRNA levels of pro-opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC), an area where mTOR co-localizes with thyroid hormone receptor-α (TRα). Central administration of thyroid hormone (T3) or genetic activation of thyroid hormone signalling in the ARC recapitulated hyperthyroidism effects on feeding and the mTOR pathway. In turn, central inhibition of mTOR signalling with rapamycin in hyperthyroid rats reversed hyperphagia and normalized the expression of ARC-derived neuropeptides, resulting in substantial body weight loss. The data indicate that in the hyperthyroid state, increased feeding is associated with thyroid hormone-induced up-regulation of mTOR signalling. Furthermore, our findings that different neuronal modulations influence food intake and energy expenditure in hyperthyroidism pave the way for a more rational design of specific and selective therapeutic compounds aimed at reversing the metabolic consequences of this disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  15. Effects of Physical Exercise on the Intestinal Mucosa of Rats Submitted to a Hypothalamic Obesity Condition.

    Science.gov (United States)

    Gomes, J R; Freitas, J R; Grassiolli, S

    2016-10-01

    The small intestine plays a role in obesity as well as in satiation. However, the effect of physical exercise on the morphology and function of the small intestine during obesity has not been reported to date. This study aimed to evaluate the effects of physical exercise on morphological aspects of the rat small intestine during hypothalamic monosodium glutamate (MSG)-induced obesity. The rats were divided into four groups: Sedentary (S), Monosodium Glutamate (MSG), Exercised (E), and Exercised Monosodium Glutamate (EMSG). The MSG and EMSG groups received a daily injection of monosodium glutamate (4 g/kg) during the 5 first days after birth. The S and E groups were considered as control groups and received injections of saline. At weaning, at 21 days after birth, the EMSG and E groups were submitted to swimming practice 3 times a week until the 90th day, when all groups were sacrificed and the parameters studied recorded. Exercise significantly reduced fat deposits and the Lee Index in MSG-treated animals, and also reduced the thickness of the intestinal wall, the number of goblet cells and intestinal alkaline phosphatase activity. However, physical activity alone increased the thickness and height of villi, and the depth of the crypts. In conclusion, regular physical exercise may alter the morphology or/and functions of the small intestine, reducing the prejudicial effects of hypothalamic obesity. Anat Rec, 299:1389-1396, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. The central role of hypothalamic inflammation in the acute illness response and cachexia.

    Science.gov (United States)

    Burfeind, Kevin G; Michaelis, Katherine A; Marks, Daniel L

    2016-06-01

    When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

    Science.gov (United States)

    Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

    2009-01-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-θ attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-θ activation, resulting in reduced insulin activity. PMID:19726875

  18. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents.

    Science.gov (United States)

    Benoit, Stephen C; Kemp, Christopher J; Elias, Carol F; Abplanalp, William; Herman, James P; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G; Holland, William L; Clegg, Deborah J

    2009-09-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.

  19. An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity.

    Science.gov (United States)

    Xiao, Yuzhong; Deng, Yalan; Yuan, Feixiang; Xia, Tingting; Liu, Hao; Li, Zhigang; Chen, Shanghai; Liu, Zhixue; Ying, Hao; Liu, Yi; Zhai, Qiwei; Guo, Feifan

    2017-06-03

    ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-α) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy-related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter. Mice with Atf4 and Atg5 double knockout in POMC neurons have reduced energy expenditure and gain more fat mass compared with PAKO mice under a HFD. Finally, the effect of Atf4 knockout in POMC neurons is possibly mediated by enhanced ATG5-dependent macroautophagy/autophagy and α-melanocyte-stimulating hormone (α-MSH) production in the hypothalamus. Together, this work not only identifies a beneficial role for ATF4 in hypothalamic POMC neurons in the regulation of obesity, but also provides a new potential therapeutic target for obesity and obesity-related metabolic diseases.

  20. Hypoglycemia: Role of Hypothalamic Glucose-Inhibited (GI) Neurons in Detection and Correction.

    Science.gov (United States)

    Zhou, Chunxue; Teegala, Suraj B; Khan, Bilal A; Gonzalez, Christina; Routh, Vanessa H

    2018-01-01

    Hypoglycemia is a profound threat to the brain since glucose is its primary fuel. As a result, glucose sensors are widely located in the central nervous system and periphery. In this perspective we will focus on the role of hypothalamic glucose-inhibited (GI) neurons in sensing and correcting hypoglycemia. In particular, we will discuss GI neurons in the ventromedial hypothalamus (VMH) which express neuronal nitric oxide synthase (nNOS) and in the perifornical hypothalamus (PFH) which express orexin. The ability of VMH nNOS-GI neurons to depolarize in low glucose closely parallels the hormonal response to hypoglycemia which stimulates gluconeogenesis. We have found that nitric oxide (NO) production in low glucose is dependent on oxidative status. In this perspective we will discuss the potential relevance of our work showing that enhancing the glutathione antioxidant system prevents hypoglycemia associated autonomic failure (HAAF) in non-diabetic rats whereas VMH overexpression of the thioredoxin antioxidant system restores hypoglycemia counterregulation in rats with type 1 diabetes.We will also address the potential role of the orexin-GI neurons in the arousal response needed for hypoglycemia awareness which leads to behavioral correction (e.g., food intake, glucose administration). The potential relationship between the hypothalamic sensors and the neurocircuitry in the hindbrain and portal mesenteric vein which is critical for hypoglycemia correction will then be discussed.

  1. Hypoglycemia: Role of Hypothalamic Glucose-Inhibited (GI Neurons in Detection and Correction

    Directory of Open Access Journals (Sweden)

    Chunxue Zhou

    2018-03-01

    Full Text Available Hypoglycemia is a profound threat to the brain since glucose is its primary fuel. As a result, glucose sensors are widely located in the central nervous system and periphery. In this perspective we will focus on the role of hypothalamic glucose-inhibited (GI neurons in sensing and correcting hypoglycemia. In particular, we will discuss GI neurons in the ventromedial hypothalamus (VMH which express neuronal nitric oxide synthase (nNOS and in the perifornical hypothalamus (PFH which express orexin. The ability of VMH nNOS-GI neurons to depolarize in low glucose closely parallels the hormonal response to hypoglycemia which stimulates gluconeogenesis. We have found that nitric oxide (NO production in low glucose is dependent on oxidative status. In this perspective we will discuss the potential relevance of our work showing that enhancing the glutathione antioxidant system prevents hypoglycemia associated autonomic failure (HAAF in non-diabetic rats whereas VMH overexpression of the thioredoxin antioxidant system restores hypoglycemia counterregulation in rats with type 1 diabetes.We will also address the potential role of the orexin-GI neurons in the arousal response needed for hypoglycemia awareness which leads to behavioral correction (e.g., food intake, glucose administration. The potential relationship between the hypothalamic sensors and the neurocircuitry in the hindbrain and portal mesenteric vein which is critical for hypoglycemia correction will then be discussed.

  2. Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis Due to Dysfunction of the Hypothalamic Glucocorticoid Receptor in Sigma-1 Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    Tingting Di

    2017-09-01

    Full Text Available Sigma-1 receptor knockout (σ1R-KO mice exhibit a depressive-like phenotype. Because σ1R is highly expressed in the neuronal cells of hypothalamic paraventricular nuclei (PVN, this study investigated the influence of σ1R deficiency on the regulation of the hypothalamic-pituitary-adrenocortical (HPA axis. Here, we show that the levels of basal serum corticosterone (CORT, adrenocorticotropic hormone (ACTH and corticotrophin releasing factor (CRF as well as the level of CRF mRNA in PVN did not significantly differ between adult male σ1R-KO mice and wild-type (WT mice. Acute mild restraint stress (AMRS induced a higher and more sustainable increase in activity of HPA axis and CRF expression in σ1R-KO mice. Percentage of dexamethasone (Dex-induced reduction in level of CORT was markedly attenuated in σ1R−/− mice. The levels of glucocorticoid receptor (GR and protein kinase C (PKC phosphorylation were reduced in the PVN of σ1R-KO mice and σ1R antagonist NE100-treated WT mice. The exposure to AMRS in σ1R-KO mice induced a stronger phosphorylation of cAMP-response element binding protein (CREB in PVN than that in WT mice. Intracerebroventricular (i.c.v. injection of PKC activator PMA for 3 days in σ1R-KO mice not only recovered the GR phosphorylation and the percentage of Dex-reduced CORT but also corrected the AMRS-induced hyperactivity of HPA axis and enhancement of CRF mRNA and CREB phosphorylation. Furthermore, the injection (i.c.v. of PMA in σ1R-KO mice corrected the prolongation of immobility time in forced swim test (FST and tail suspension test (TST. These results indicate that σ1R deficiency causes down-regulation of GR by reducing PKC phosphorylation, which attenuates GR-mediated feedback inhibition of HPA axis and facilitates the stress response of HPA axis leading to the production of depressive-like behaviors.

  3. Hypothalamic tumor

    Science.gov (United States)

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  4. Hypothalamic dysfunction

    Science.gov (United States)

    ... apoplexy , subarachnoid hemorrhage Genetic disorders, such as Prader-Willi syndrome , familial diabetes insipidus , Kallmann syndrome Infections and ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  5. Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea.

    Science.gov (United States)

    Carmina, Enrico; Fruzzetti, Franca; Lobo, Roger A

    2016-06-01

    Functional hypothalamic amenorrhea is a disorder characterized by cessation of menstrual cycles in the absence of organic disease. In most patients, it occurs in adult life after a stressful event and may be related to a condition of mild chronic energy deprivation. The endocrine pattern is characterized by low estrogen levels with an absent response to a progestogen challenge test and low-normal gonadotropin levels. A few studies have shown that some of these women may have some features of polycystic ovary syndrome; these features include an increased androgen response to gonadotropins, increased anti-Mullerian hormone levels, and altered ovarian morphology or increased ovarian size. These findings suggest a link between these 2 completely different disorders: functional hypothalamic amenorrhea and polycystic ovary syndrome. The importance of the possible coexistence of these disorders in some women is important for follow-up of these women and in their treatment if they desire to become pregnant. To determine whether a subgroup of well-characterized women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Retrospective analysis of women with functional hypothalamic amenorrhea. Forty consecutive patients and 28 normal age-matched control patients were studied. Blood was obtained for serum anti-Mullerian hormone, androgens, and other hormone levels and all women had ovarian ultrasonographic measurements. In the entire group of women with functional hypothalamic amenorrhea, anti-Mullerian hormone and ovarian volume were greater than in control patients. In 13 patients (32.5%), anti-Mullerian hormone was elevated (>4.7 ng/mL, levels consistent with polycystic ovary syndrome) and in this group, ovarian volume was significantly greater than in the remaining patients with functional hypothalamic amenorrhea. Four of the 13 women with functional hypothalamic amenorrhea who had elevated anti-Mullerian hormone levels (10%), also

  6. Hypothalamic regulation of thyroid-stimulating hormone and prolactin release : the role of thyrotrophin-releasing hormone

    NARCIS (Netherlands)

    G.A.C. van Haasteren (Goedele)

    1995-01-01

    textabstractThyrotrophin-releasing-hormone (TRH), a tripeptide, is produced by hypothalamic neurons and transported along their axons to the median eminence (ME). From there it is released at nerve terminals into hypophyseal portal blood. It is then transported to the anterior pituitary gland where

  7. Anesthetic considerations for rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction (ROHHAD) syndrome in children.

    Science.gov (United States)

    Chandrakantan, Arvind; Poulton, Thomas J

    2013-01-01

    Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction is an increasingly common diagnosis in patients who are being seen at tertiary care children's hospitals. We present two cases of anesthetics from the authors' own experience in addition to a comprehensive review of the disorder and anesthetic implications. © 2012 Blackwell Publishing Ltd.

  8. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus

    Science.gov (United States)

    The transcription factor steroidogenic factor 1 (SF-1) is exclusively expressed in the brain in the ventral medial hypothalamic nucleus (VMH) and is required for the development of this nucleus. However, the physiological importance of transcriptional programs regulated by SF-1 in the VMH is not wel...

  9. PI3K in the ventromedial hypothalamic nucleus mediates estrogenic actions on energy expenditure in female mice

    Science.gov (United States)

    Estrogens act in the ventromedial hypothalamic nucleus (VMH) to regulate body weight homeostasis. However, the molecular mechanisms underlying these estrogenic effects are unknown. We show that activation of estrogen receptor-a (ERa) stimulates neural firing of VMH neurons expressing ERa, and these ...

  10. Hypothalamic kappa opioid receptor mediates both diet- and MCH-induced liver damage through inflammation and ER stress

    NARCIS (Netherlands)

    Imbernon, Monica; Sanchez-Rebordelo, Estrella; Romero-Picó, Amparo; Kalló, Imre; Chee, Melissa J; Porteiro, Begoña; Al-Massadi, Omar; Contreras, Cristina; Fernø, Johan; Senra, Ana; Gallego, Rosalia; Folgueira, Cintia; Seoane, Luisa M; van Gestel, Margriet; Adan, Roger A; Liposits, Zsolt; Dieguez, Carlos; Lopez, Miguel; Nogueiras, Ruben

    2016-01-01

    The opioid system is widely known to modulate the brain reward system and thus affect human and animal behaviour, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and

  11. If It Goes up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary Adrenocortical Axis in Humans

    Science.gov (United States)

    Miller, Gregory E.; Chen, Edith; Zhou, Eric S.

    2007-01-01

    The notion that chronic stress fosters disease by activating the hypothalamic-pituitary adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed…

  12. Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems

    International Nuclear Information System (INIS)

    Audhya, T.; Manzione, M.M.; Nakane, T.; Kanie, N.; Passarelli, J.; Russo, M.; Hollander, C.S.

    1985-01-01

    Polyclonal antibodies to synthetic human pancreatic growth hormone-releasing factor [hpGRF(1-44)NH 2 ] and rat hypothalamic growth hormone-releasing factor [rhGRF(1-43)OH] were produced in rabbits. A subsequent booster injection by the conventional intramuscular route resulted in high-titer antibodies, which at a 1:20,000 dilution were used to develop highly sensitive and specific radioimmunoassays for these peptides. The antibody to hpGRF(1-44)NH 2 is directed against the COOH-terminal region of the molecule, as shown by its cross reactivity with various hpGRF analogues. Serial dilutions of human and rat hypothalamic extracts demonstrated parallelism with the corresponding species-specific standard and 125 I-labeled tracer. There was no cross reactivity with other neuropeptides, gastrointestinal peptides, or hypothalamic extracts of other species. Age-related changes in hypothalamic GRF content were present in rats, with a gradual increase from 2 to 16 weeks and a correlation between increasing body weight and GRF content. These radioimmunoassays will serve as important tools for understanding the regulation of growth hormone secretion in both human and rat

  13. Effects of Parental Depressive Symptoms on Child Adjustment Moderated by Hypothalamic Pituitary Adrenal Activity: Within- and between-Family Risk

    Science.gov (United States)

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Fisher, Philip A.; Marceau, Kristine; Harold, Gordon T.; Reiss, David

    2013-01-01

    Child hypothalamic pituitary adrenal (HPA) activity was investigated as a moderator of parental depressive symptom effects on child behavior in an adoption sample ("n" = 210 families). Adoptive parents' depressive symptoms and child internalizing and externalizing were assessed at 18, 27, and 54 months, and child morning and evening HPA…

  14. Predicting Adaptive Response to Fadrozole Exposure:Computational Model of the Fathead MinnowsHypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course (...

  15. Adaptive Response in Female Fathead Minnows Exposed to an Aromatase Inhibitor: Computational Modeling of the Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

  16. Predicting Adaptive Response to Fadrozole Exposure: Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (...

  17. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2012-01-01

    Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

  18. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2015-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  19. Irradiation of the hypothalamic-hypophyseal area induces complete regression of mucocutaneous lesions in disseminated histiocytosis X

    International Nuclear Information System (INIS)

    Palmieri, G.; Stefani, S.; Gridelli, C.; Conte, A.; Airoma, G.; Contegiacomo, A.; Bianco, A.R.

    1989-01-01

    We report on a 54-year-old woman with disseminated histiocytosis X who had a complete regression of all mucocutaneous lesions within 1 month from the completion of radiation therapy (4500 cGy) to the hypothalamic-hypophyseal (H-H) area. This response lasted 12 months, after which new cutaneous and bone lesions appeared

  20. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2017-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate