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Sample records for human hypothalamus autoradiographic

  1. Autoradiographic and ultrastructural studies on the human fibro-atheromatous plaque

    Energy Technology Data Exchange (ETDEWEB)

    Villaschi, S.; Spagnoli, L.G. (Universita degli Studi, Rome (Italy). Istituto di Anatomia ed Istologia Patologica)

    1983-07-01

    Foam cells, either myogenic or macrophagic, are commonly detected in experimental and human fibro-atheromatous plaques. Their role in human atherosclerosis is not yet understood. This paper reports on a preliminary autoradiographic study combined with ultrastructural observations in the human fibro-atheromatous plaque. Most of the autoradiographic silver grains appeared on foam cells and monocytelike cells, thus suggesting a local proliferation of these cells.

  2. Autoradiographic and ultrastructural studies on the human fibro-atheromatous plaque

    International Nuclear Information System (INIS)

    Villaschi, Sergio; Spagnoli, L.G.

    1983-01-01

    Foam cells, either myogenic or macrophagic, are commonly detected in experimental and human fibro-atheromatous plaques. Their role in human atherosclerosis is not yet understood. This paper reports on a preliminary autoradiographic study combined with ultrastructural observations in the human fibro-atheromatous plaque. Most of the autoradiographic silver grains appeared on foam cells and monocytelike cells, thus suggesting a local proliferation of these cells. (author)

  3. Sexual differentiation of the human hypothalamus

    NARCIS (Netherlands)

    Swaab, Dick F.; Chung, Wilson C. J.; Kruijver, Frank P. M.; Hofman, Michael A.; Ishunina, Tatjana A.

    2002-01-01

    Functional sex differences in reproduction, gender and sexual orientation and in the incidence of neurological and psychiatric diseases are presumed to be based on structural and functional differences in the hypothalamus and other limbic structures. Factors influencing gender, i.e., the feeling to

  4. Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

    NARCIS (Netherlands)

    Borgers, A.J.; Alkemade, A.; Van de Giessen, E.M.; Drent, M.L.; Booij, J.; Bisschop, P.H.; Fliers, E.

    2013-01-01

    Background: Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is

  5. Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus

    NARCIS (Netherlands)

    Alkemade, Anneke; Friesema, Edith C.; Unmehopa, Unga A.; Fabriek, Babs O.; Kuiper, George G.; Leonard, Jack L.; Wiersinga, Wilmar M.; Swaab, Dick F.; Visser, Theo J.; Fliers, Eric

    2005-01-01

    Context: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. Objective: The aim of this study was to report the

  6. The accessory magnocellular neurosecretory system of the rostral human hypothalamus

    DEFF Research Database (Denmark)

    Møller, Morten; Busch, Johannes R.; Jacobsen, Christina

    2018-01-01

    magnocellular neurons were often located along the blood vessels and projections of some of these neurons penetrated the vascular endothelium. The accessory magnocellular cell bodies expressed either neurophysin I or neurophysin II immunoreactivity. Summarizing, the accessory magnocellular system in the human......The morphology and neurophysin expression of the magnocellular accessory neuroendocrine system located in the rostral human hypothalamus is investigated in a series of brains obtained at autopsy. The hypothalami were fixed in formalin and embedded in paraffin, or after cryoprotection, frozen...

  7. Autoradiographic quantification of vasoactive intestinal peptide binding sites in sections from human blood mononuclear cell pellets

    Energy Technology Data Exchange (ETDEWEB)

    Gutkind, J.S.; Kurihara, M.; Castren, E.; Saavedra, J.M.

    1988-09-01

    Quantitative autoradiographic methods were utilized to characterize specific, high-affinity vasoactive intestinal peptide binding sites (Kd = 310 +/- 60 pmol/L; Bmax = 93 +/- 11 fmol/mg protein) in frozen sections obtained from a mononuclear cell pellet derived from 20 ml of human blood. The method is at least one order of magnitude more sensitive than conventional membrane binding techniques, and it has the potential for wide applications in studies of neuropeptide, biogenic amine, and drug binding in clinical samples.

  8. Autoradiographic quantification of vasoactive intestinal peptide binding sites in sections from human blood mononuclear cell pellets

    International Nuclear Information System (INIS)

    Gutkind, J.S.; Kurihara, M.; Castren, E.; Saavedra, J.M.

    1988-01-01

    Quantitative autoradiographic methods were utilized to characterize specific, high-affinity vasoactive intestinal peptide binding sites (Kd = 310 +/- 60 pmol/L; Bmax = 93 +/- 11 fmol/mg protein) in frozen sections obtained from a mononuclear cell pellet derived from 20 ml of human blood. The method is at least one order of magnitude more sensitive than conventional membrane binding techniques, and it has the potential for wide applications in studies of neuropeptide, biogenic amine, and drug binding in clinical samples

  9. Autoradiographic detection of diphtheria toxin resistant mutants in human diploid fibroblasts

    International Nuclear Information System (INIS)

    Gupta, R.S.; Singh, B.

    1985-01-01

    An autoradiographic procedure for the detection of diphtheria toxin (DT) resistant (Dip/sub R/) mutants in human diploid fibroblast (HDF) cells has been developed. The assay is based on the observation that when HDFs from confluent cultures are seeded in medium containing 0.01 flocculating units/ml or higher concentration of DT, protein synthesis in sensitive cells is severely inhibited by 4-6 hr. If at this or later time, a radiolabeled protein precursor (eg, 3 H-leucine) is added to the culture, it is almost exclusively incorporated into the resistant cells, which are then readily identified by autoradiography. These studies provide strong evidence that the labeled cells identified by autoradiography are bona fide Dip/sub R/ mutants. The detection of Dip/sub R/ cells by autoradiography is apparently not affected by the presence of the sensitive cells in the mixtures. The spontaneous frequency of Dip/sub R/ cells in HDFs has been found to be in the range of 1-5 x 10 -6 , and this increases in a dose dependent manner upon treatment with the mutagen ethyl methanesulfonate. These results indicate that the autoradiographic assay could be used for quantitative mutagenesis. Since the autoradiographic assay does not depend on cell division, it may prove useful in estimating the incidence of pre-existing mutations in cell populations that either do not divide or have very limited growth potential (eg, lymphocytes, muscle cells, neurons, senescent fibroblasts, etc.)

  10. High resolution autoradiographic studies of RNA, protein and DNA synthesis during human eosinophil granulocytopoiesis

    International Nuclear Information System (INIS)

    Wickramasinghe, S.N.; Hughes, M.

    1978-01-01

    Human bone marrow cells which had been incubated with [ 3 H] uridine or [ 3 H]leucine for 1 h were studied using the technique of electron microscope-autoradiography. The autoradiographs revealed the presence of newly-synthesized RNA and protein molecules within or on a proportion of (1) the primary and secondary granules in all classes of eosinophil precursors and (2) the secondary granules in eosinophil granulocytes. It is suggested that the granule-associated RNA molecules may be concerned with the synthesis of at least some of the new protein molecules which were incorporated into the limiting membrane or substance of eosinophil granules long after the immature primary granule stage. Studies of eosinophil precursors which had been incubated with [ 3 H]thymidine for 1 h showed that the eosinophil granules did not label with this DNA precursor. (author)

  11. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

    International Nuclear Information System (INIS)

    Mak, J.C.; Barnes, P.J.

    1990-01-01

    Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](-)quinuclidinyl benzilate [( 3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies

  12. In vitro autoradiographic studies for determination of mitotic index and labelling index in biopsies of the human oral mucosa

    International Nuclear Information System (INIS)

    Etzbach, T.

    1980-01-01

    In order to find the most favourable method of incubation for in-vitro autoradiographies of biopsies of human oral mucosa, tissue biopsies were taken from oral mucosa transplants of 10 patients (7 females, 3 males) and either fixed or incubated at once. The author then investigated the mitotic index of the non-incubated tissue specimens, the mitotic index of the tissue specimens incubated in atmospheric conditions (A), and the mitotic index of the tissue specimens incubated under pressure (B). Simultaneously, autoradiographs of the incubated tissue specimens were prepared in order to determine their labelling indices. The mitotic indices of the non-incubated tissue specimen were found to differ significantly from those of the A-incubated tissue specimens. A similar difference was found between the mitotic indices of the A- and B-incubated tissue biopsies. Further, the labelling indices of A autoradiographs differed significantly from the labelling indices of B autoradiographs. The findings suggest that incubation with an excess oxygen pressure of 2 bar is the method of choice for in-vitro studies of human oral mucosa as the cells retain their specific activity and cell processes will continue unhindered. Further, the findings can be transferred to in-vivo conditions with a reasonable error rate. (orig./MG) [de

  13. Anatomy of the human hypothalamus (chiasmatic and tuberal region).

    Science.gov (United States)

    Braak, H; Braak, E

    1992-01-01

    The hypothalamus sensu stricto consists of the chiasmatic, the tuberal and the mamillary region. The present study is confined to the poorly myelinated chiasmatic and tuberal region. Both regions harbor many nuclear grays with relatively clear-cut boundaries embedded in an ill-defined nerve cell assembly referred to as the hypothalamic gray. Prominent components of the chiasmatic region are the magnocellular neurosecretory complex (supraoptic nucleus, paraventricular nucleus, accessory neurosecretory nucleus), the sexually dimorphic intermediate nucleus, the suprachiasmatic and retrochiasmatic nuclei. The dominating structure of the tuberal region is the complex of the ventromedial, posteromedial and dorsomedial nuclei supplemented by the periventricular and infundibular nuclei. Lateral portions of the tuber cinereum harbor the lateral tuberal nucleus and the tuberomamillary nucleus. The lateral tuberal nucleus exhibits pronounced cell loss in Huntington's chorea and is also severely involved in cases of dementia with argyrophilic grains. The large nerve cells of the tuberomamillary nucleus show particularly severe affection in both Alzheimer's (intraneuronal neurofibrillary changes) and Parkinson's disease (Lewy bodies).

  14. Sex differences in the hypothalamus in the different stages of human life

    NARCIS (Netherlands)

    Swaab, Dick F.; Chung, Wilson C. J.; Kruijver, Frank P. M.; Hofman, Michel A.; Hestiantoro, Andon

    2003-01-01

    Quite a number of structural and functional sex differences have been reported in the human hypothalamus and adjacent structures that may be related to not only reproduction, sexual orientation and gender identity, but also to the often pronounced sex differences in prevalence of psychiatric and

  15. Activation and degeneration during aging: a morphometric study of the human hypothalamus

    NARCIS (Netherlands)

    Zhou, J. N.; Swaab, D. F.

    1999-01-01

    During the course of aging both activation and degenerative changes are found in the human hypothalamus. Degeneration may start around middle-age in some neurotransmitter- or neuromodulator-containing neurons. For instance, a decreased number of vasoactive intestinal polypeptide (VIP) neurons was

  16. Estrogen receptor-alpha distribution in the human hypothalamus in relation to sex and endocrine status

    NARCIS (Netherlands)

    Kruijver, Frank P. M.; Balesar, Rawien; Espila, Ana M.; Unmehopa, Unga A.; Swaab, Dick F.

    2002-01-01

    The present study reports the first systematic rostrocaudal distribution of estrogen receptor-a immunoreactivity (ERalpha-ir) in the human hypothalamus and its adjacent areas in young adults. Postmortem material taken from 10 subjects (five male and five female), between 20 and 39 years of age, was

  17. Automated analysis of autoradiographic imagery

    International Nuclear Information System (INIS)

    Bisignani, W.T.; Greenhouse, S.C.

    1975-01-01

    A research programme is described which has as its objective the automated characterization of neurological tissue regions from autoradiographs by utilizing hybrid-resolution image processing techniques. An experimental system is discussed which includes raw imagery, scanning an digitizing equipments, feature-extraction algorithms, and regional characterization techniques. The parameters extracted by these algorithms are presented as well as the regional characteristics which are obtained by operating on the parameters with statistical sampling techniques. An approach is presented for validating the techniques and initial experimental results are obtained from an anlysis of an autoradiograph of a region of the hypothalamus. An extension of these automated techniques to other biomedical research areas is discussed as well as the implications of applying automated techniques to biomedical research problems. (author)

  18. Autoradiographic localization of calcitonin gene-related peptide (CGRP) binding sites in human and guinea pig lung

    International Nuclear Information System (INIS)

    Mak, J.C.; Barnes, P.J.

    1988-01-01

    125 I-Human calcitonin gene-related peptide (hCGRP) binding sites were localized in human and guinea pig lungs by an autoradiographic method. Scatchard analysis of saturation experiments from slide-mounted sections of guinea pig lung displayed specific 125 I-hCGRP binding sites with a dissociation constant (Kd) of 0.72 +/- 0.05 nM (mean +/- S.E.M., n = 3) and a maximal number of binding sites (Bmax) of 133.4 +/- 5.6 fmol/mg protein. In both human and guinea pig lung, autoradiography revealed that CGRP binding sites were widely distributed, with particularly dense labeling over bronchial and pulmonary blood vessels of all sizes and alveolar walls. Airway smooth muscle and epithelium of large airways was sparsely labeled but no labeling was found over submucosal glands. This localization corresponds well to the reported pattern of CGRP-like immunoreactive innervation. The findings of localization of CGRP binding sites on bronchial and pulmonary blood vessels indicate that CGRP may be important in the regulation of airway and pulmonary blood flow

  19. The autoradiographic pattern of the in vitro uptake of proline by the coronal areas of intact and carious human teeth

    International Nuclear Information System (INIS)

    Karjalainen, S.; Soederling, E.

    1979-01-01

    The biosynthesis of collagen in teeth was studied by following the uptake of proline in vitro. Whole crowns of human teeth were incubated for 6 h with ( 14 C)- or ( 3 H)-proline. Autoradiographs were prepared from sections of intact teeth and teeth with carious lesions of varying depths and location. The number of silver grains per cm 2 in the predentine, odontoblast layer and pulp were counted in selected fields magnified x 430 representing the deepest parts of the carious lesions. No differences in the labelling pattern were observed between the intact teeth incubated freshly after extraction and those preserved in liquid nitrogen. The densest labelling of intact teeth was seen in the predentine and odontoblast layer. The alterations under initial dentine caries appeared as increased labelling of the predentine and decreased labelling of the odontoblast layer; no alterations were observed in the underlying pulp. In advanced lesions, the predentine labelling decreased and that in the odontoblast layer and pulp increased. In the initial stages, caries seem to activate collagen synthesis in a relatively restricted area of the underlying structures, but in advanced stages, caries seem to increase the odontoblastic cellular polypeptide chain formation but prevent further maturation of the collagen. (author)

  20. Autoradiographic pattern of the in vitro uptake of proline by the coronal areas of intact and carious human teeth

    Energy Technology Data Exchange (ETDEWEB)

    Karjalainen, S; Soederling, E [Turku Univ. (Finland)

    1979-01-01

    The biosynthesis of collagen in teeth was studied by following the uptake of proline in vitro. Whole crowns of human teeth were incubated for 6 h with (/sup 14/C)- or (/sup 3/H)-proline. Autoradiographs were prepared from sections of intact teeth and teeth with carious lesions of varying depths and location. The number of silver grains per cm/sup 2/ in the predentine, odontoblast layer and pulp were counted in selected fields magnified x 430 representing the deepest parts of the carious lesions. No differences in the labelling pattern were observed between the intact teeth incubated freshly after extraction and those preserved in liquid nitrogen. The densest labelling of intact teeth was seen in the predentine and odontoblast layer. The alterations under initial dentine caries appeared as increased labelling of the predentine and decreased labelling of the odontoblast layer; no alterations were observed in the underlying pulp. In advanced lesions, the predentine labelling decreased and that in the odontoblast layer and pulp increased. In the initial stages, caries seem to activate collagen synthesis in a relatively restricted area of the underlying structures, but in advanced stages, caries seem to increase the odontoblastic cellular polypeptide chain formation but prevent further maturation of the collagen.

  1. Partial characterization of insulin-like growth factor I in primary human lung cancers using immunohistochemical and receptor autoradiographic techniques

    International Nuclear Information System (INIS)

    Shigematsu, K.; Kataoka, Y.; Kamio, T.; Kurihara, M.; Niwa, M.; Tsuchiyama, H.

    1990-01-01

    We investigated primary human lung cancers resected surgically or obtained at autopsy. Included were squamous cell carcinoma (SQC) (five cases), adenocarcinoma (ADC) (six cases), large cell carcinoma (LCC) (four cases), and small cell carcinoma (SCC) (two cases). The objective of the study was to search for the presence of insulin-like growth factor I (IGF-I)-like immunoreactivity using immunohistochemical staining and for the localization of IGF-I binding sites, using in vitro quantitative receptor autoradiographic techniques. IGF-I-like immunostaining was present in all cases of SQC, ADC, and LCC, but not in cases of SCC. Strong immunostaining was observed in cases of SQC. On the other hand, ADC and LCC tissues showed a moderate or weak staining. Specific binding sites for IGF-I were present in all cases of SQC, ADC, LCC, and SCC examined. High densities of 125I-IGF-I binding sites were localized in cases of SQC and SCC. Low to high densities of the binding sites were found in LCC. Cases of ADC showed low densities of 125I-IGF-I binding sites. Specific binding obtained at a concentration of 80 pM 125I-IGF-I was competitively displaced by unlabeled IGF-I, with a 50% inhibitory concentration value of 1.84 +/- 0.31 x 10(-10) mol, whereas human insulin was much less potent in displacing the binding. This specificity profile is consistent with characteristics of IGF-I receptors. Scatchard analysis showed the presence of a single class of high affinity binding sites for IGF-I, with a Kd of approximately 1 nmol. Thus, the possibility that IGF-I may play a role in the growth of human lung cancers would have to be considered

  2. Autoradiographic studies and experiments on partical synchronization of human tumors, especially mammary carcinomas, in vitro and in vivo following xenotransplantation to NU/NU mice

    International Nuclear Information System (INIS)

    Nord, D.

    1980-01-01

    Human mammary carcinomes were evaluated radiographically in vitro in the native state. Penetration dephts up to 552 μm into the tissue were reached by the incubating medium. The labelling indices for the 3H-thymidine autoradiography lay between 1.5 and 19.3 percent. A correlation of the autoradiographic labelling indices with the findings of a simultaneously performed in vitro sensitivity test against cytostalics could not be proved. There seems to be a relation between the histomorphological tumour image and the proliferation behaviour expressed by the autoradiographic labelling index. Human mammary carcinomes were cultivated as xeno-transplant on thymus-aplastic NU/NU mice in parallel to this investigation. These heterotransplants show a remarkable correlation to the proliferation behaviour of the directly examined human tumours, after an autoradiographic in-vivo-labelling, with index values between 1.5 and 23.8 percent. This parallelism in the biological behaviour represents a further proof for the usefulness of the oncological test model of the NU/NU mouse as a carrier for human cacinomes. The application of this pre-therapeutical test model followed by determination of the synchronization behaviour of three human malignomas after xeno-transplantation onto NU/NU mice. For all three tumous an individual synchronization behaviour could be determined. Therapy attempts followed with cyclophosphonide or ionizing radiation by using the optimal cell-cycle therapy. Therefore an improvement of the therapeutical success by means of pre-therapeutical synchronization of human tumours can be reached in particular cases. (orig./MG) [de

  3. Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS

    NARCIS (Netherlands)

    Purba, J. S.; Hofman, M. A.; Portegies, P.; Troost, D.; Swaab, D. F.

    1993-01-01

    The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age

  4. Volumetric parcellation methodology of the human hypothalamus in neuroimaging: normative data and sex differences

    NARCIS (Netherlands)

    Makris, Nikos; Swaab, Dick F.; van der Kouwe, Andre; Abbs, Brandon; Boriel, Denise; Handa, Robert J.; Tobet, Stuart; Goldstein, Jill M.

    2013-01-01

    There is increasing evidence regarding the importance of the hypothalamus for understanding sex differences in relation to neurological, psychiatric, endocrine and sleep disorders. Although different in histology, physiology, connections and function, multiple hypothalamic nuclei subserve

  5. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

    International Nuclear Information System (INIS)

    Gross-Isseroff, R.; Dillon, K.A.; Fieldust, S.J.; Biegon, A.

    1990-01-01

    In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measured by autoradiography

  6. Autoradiographic studies on the cell proliferation of the human chronic gastritis

    International Nuclear Information System (INIS)

    Yagami, Yoshifumi

    1982-01-01

    Cell proliferation of human gastric mucosa was studied in the cases of chronic gastritis using the in vitro incubation method of 3 H-thymidine autoradiography. The study was carried out using the material consisted of 92 biopsy specimens and 83 stomachs diagnosed as carcinoma, peptic ulcer, duodenal ulcer and chronic gastritis. The labelling index was expressed in a percentage of labelled cells in ratio to the total number of epithelial cells. In the normal gastric mucosae, 3 H-TdR labeled cells were in the neck region of the gastric gland, but did not appear in the surface epithelium. Higher incorporation of 3 H-TdR was observed in the lower part of the neck region of the glands. The average indices, both labeling and mitotic, were generally higher in the antrum than in the pylorus in the cases of chronic gastritis and also higher than normal mucosae. Superficial gastritis showed many labeled cells which were located in the neck region and foveolae. Simple gastitis showed scattered labeled cells in various parts of mucosae. In atrophic and atrophic hyperplastic gastritis, labeled cells were found in the neck and fobeolae of the gastric glands. Metaplastic gastritis showed labeled cells especially in the neck regions. The average labeling index is higher in simple chronic gastritis than in other superficial gastritis, atrophic, atrophic hyperplastic and metaplastic gastritis. Information concerned with cell renewal and proliferation is important for further understanding of the development of disease. (J.P.N.)

  7. Autoradiographic studies on the cell proliferation of the human chronic gastritis

    Energy Technology Data Exchange (ETDEWEB)

    Yagami, Y. (Nippon Medical School, Tokyo)

    1982-02-01

    Cell proliferation of human gastric mucosa was studied in the cases of chronic gastritis using the in vitro incubation method of /sup 3/H-thymidine autoradiography. The study was carried out using the material consisted of 92 biopsy specimens and 83 stomachs diagnosed as carcinoma, peptic ulcer, duodenal ulcer and chronic gastritis. The labelling index was expressed in a percentage of labelled cells in ratio to the total number of epithelial cells. In the normal gastric mucosae, /sup 3/H-TdR labeled cells were in the neck region of the gastric gland, but did not appear in the surface epithelium. Higher incorporation of /sup 3/H-TdR was observed in the lower part of the neck region of the glands. The average indices, both labeling and mitotic, were generally higher in the antrum than in the pylorus in the cases of chronic gastritis and also higher than normal mucosae. Superficial gastritis showed many labeled cells which were located in the neck region and foveolae. Simple gastitis showed scattered labeled cells in various parts of mucosae. In atrophic and atrophic hyperplastic gastritis, labeled cells were found in the neck and fobeolae of the gastric glands. Metaplastic gastritis showed labeled cells especially in the neck regions. The average labeling index is higher in simple chronic gastritis than in other superficial gastritis, atrophic, atrophic hyperplastic and metaplastic gastritis. Information concerned with cell renewal and proliferation is important for further understanding of the development of disease.

  8. Autoradiographic studies on nucleic acid synthesis of human gastric cancer cells, 1. Relationship between nucleic acid synthesis of cancer cells and clinicopathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, K [Kobe Univ. (Japan). School of Medicine

    1982-03-01

    The rate of nucleic acid synthesis of human gastric cancer cells was studied autoradiographically and was compared with clinicopathological findings. 1) /sup 3/H-thymidine labeling index (TLI, mean 22.4%, n = 21) ranged from 6.2% to 39.5%. Mitotic index (mean 1.96%) ranged from 1.18% to 3.48%. 2) Average TLIs in the cancerous lesions with serosal invasion, in microscopical stages III and IV, in scirrhous type and in cancer cells locating in pm- and ss-layers showed lower values compared with the counterparts. 3) /sup 3/H-uridine labeling index (mean 92.7%) ranged from 75.0% to 99.8%.

  9. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity

    NARCIS (Netherlands)

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P. M.; Swaab, Dick F.

    2011-01-01

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir)

  10. TUB gene expression in hypothalamus and adipose tissue and its association with obesity in humans

    NARCIS (Netherlands)

    Nies, V J M; Struik, D; Wolfs, M G M; Rensen, S S; Szalowska, E; Unmehopa, U A; Fluiter, K.; van der Meer, T P; Hajmousa, G; Buurman, W A; Greve, J W; Rezaee, F; Shiri-Sverdlov, R; Vonk, R.J.; Swaab, D F; Wolffenbuttel, B H R; Jonker, J W; van Vliet-Ostaptchouk, J V

    2018-01-01

    BACKGROUND/OBJECTIVES: Mutations in the Tubby gene (TUB) cause late-onset obesity and insulin resistance in mice and syndromic obesity in humans. Although TUB gene function has not yet been fully elucidated, studies in rodents indicate that TUB is involved in the hypothalamic pathways regulating

  11. TUB gene expression in hypothalamus and adipose tissue and its association with obesity in humans

    NARCIS (Netherlands)

    Nies, V. J. M.; Struik, D.; Wolfs, M. G. M.; Rensen, S. S.; Szalowska, E.; Unmehopa, U. A.; Fluiter, K.; van der Meer, T. P.; Hajmousa, G.; Buurman, W. A.; Greve, J. W.; Rezaee, F.; Shiri-Sverdlov, R.; Vonk, R. J.; Swaab, D. F.; Wolffenbuttel, B. H. R.; Jonker, J. W.; van Vliet-Ostaptchouk, J. V.

    2017-01-01

    Mutations in the Tubby gene (TUB) cause late-onset obesity and insulin resistance in mice and syndromic obesity in humans. Although TUB gene function has not yet been fully elucidated, studies in rodents indicate that TUB is involved in the hypothalamic pathways regulating food intake and adiposity.

  12. TUB gene expression in hypothalamus and adipose tissue and its association with obesity in humans

    NARCIS (Netherlands)

    Nies, V J M; Struik, D; Wolfs, M G M; Rensen, S S; Szalowska, E; Unmehopa, U A; Fluiter, K; van der Meer, T P; Hajmousa, G; Buurman, W A; Greve, J W; Rezaee, F; Shiri-Sverdlov, R; Vonk, R J; Swaab, D F; Wolffenbuttel, B H R; Jonker, J W; van Vliet-Ostaptchouk, J V

    BACKGROUND/OBJECTIVES: Mutations in the Tubby gene (TUB) cause late-onset obesity and insulin resistance in mice and syndromic obesity in humans. Although TUB gene function has not yet been fully elucidated, studies in rodents indicate that TUB is involved in the hypothalamic pathways regulating

  13. Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using 125I-Bolton-Hunter-CCK8

    International Nuclear Information System (INIS)

    Niehoff, D.L.

    1989-01-01

    The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, 125 I-Bolton-Hunter-CCK8 ( 125 I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of 125 I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species

  14. Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

    Science.gov (United States)

    Grassi, G; Seravalle, G; Dell'Oro, R; Turri, C; Pasqualinotto, L; Colombo, M; Mancia, G

    2001-12-01

    Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

  15. Platelet-derived growth factor receptors in the human central nervous system : autoradiographic distribution and receptor densities in multiple sclerosis

    NARCIS (Netherlands)

    De Keyser, J; Wilczak, N

    1997-01-01

    Platelet derived growth factor (PDGF) receptors were studied in postmortem adult human brain and cervical spinal cord using autoradiography with human recombinant I-125-PDGF-BB. PDGF-BB binds to the three different dimers of PDGF receptors (alpha alpha, alpha beta and beta beta) PDGF receptors were

  16. Receptors for corticotropin-releasing hormone in human pituitary: Binding characteristics and autoradiographic localization to immunocytochemically defined proopiomelanocortin cells

    Energy Technology Data Exchange (ETDEWEB)

    Smets, G.; Vauquelin, G.; Moons, L.; Smitz, J.; Kloeppel, G. (Department of Experimental Pathology, Vrije Universiteit Brussel (Belgium))

    1991-08-01

    Using autoradiography combined with immunocytochemistry, the authors demonstrated that the target cells of CRH in the human pituitary were proopiomelanocortin cells. Scatchard analysis of (125I)Tyr0-oCRH saturation binding revealed the presence of one class of saturable, high affinity sites on pituitary tissue homogenate. The equilibrium dissociation constant (Kd) for (125I)Tyr0-oCRH ranged from 1.1-1.6 nM, and the receptor density was between 200-350 fmol/mg protein. Fixation of cryostat sections with 4% paraformaldehyde before tracer incubation improved both tissue preservation and localization of the CRH receptor at the cellular level. Additional postfixation with 1% glutaraldehyde inhibited tracer diffusion during subsequent immunocytochemistry and autoradiography. (125I)Tyr0-oCRH was found in cytoplasmic inclusions or at the cell periphery of ACTH/beta-endorphin cells in the anterior pituitary. Single cells of the posterior pituitary were also CRH receptor positive. Cells staining for PRL or GH were CRH receptor negative. They conclude that CRH binds only to high affinity receptors on ACTH/{beta}-endorphin cells in the human pituitary.

  17. Possible distortion of autoradiographic results

    Energy Technology Data Exchange (ETDEWEB)

    Kozlov, A.A.; Tumanushvili, G.D. (AN Gruzinskoj SSR, Tbilisi. Inst. Ehksperimental' noj Morfologii)

    1980-01-01

    The effect of radioactive labelling (H/sup 3/-thymidine) on the infusorian division is studied. The presented results show that introduction of labelled compounds results in accelerating infusorian cell division v. Thorough investigation of labelled compound effect with low activity on the parameters of cell division and the search of methods to eliminate distortions able to appear in autoradiographic experiments is expedient.

  18. Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.

    Science.gov (United States)

    Bernstein, Hans-Gert; Müller, Susan; Dobrowolny, Hendrik; Wolke, Carmen; Lendeckel, Uwe; Bukowska, Alicja; Keilhoff, Gerburg; Becker, Axel; Trübner, Kurt; Steiner, Johann; Bogerts, Bernhard

    2017-08-01

    The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.

  19. Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using sup 125 I-Bolton-Hunter-CCK8

    Energy Technology Data Exchange (ETDEWEB)

    Niehoff, D.L. (Abbott Laboratories, Abbott Park, IL (USA))

    1989-03-01

    The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, {sup 125}I-Bolton-Hunter-CCK8 ({sup 125}I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of {sup 125}I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species.

  20. Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala and ventral striatum

    Science.gov (United States)

    Fletcher, PC; Napolitano, A; Skeggs, A; Miller, SR; Delafont, B; Cambridge, VC; de Wit, S; Nathan, PJ; Brooke, A; O’Rahilly, S; Farooqi, IS; Bullmore, ET

    2012-01-01

    We used fMRI to explore brain responses to food images in overweight humans, examining independently the impact of a pre-scan meal (“satiety”) and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly different responses to these manipulations in amygdala, hypothalamus and ventral striatum. Each region was specifically responsive to high calorie compared to low calorie food images. However, the ventral striatal response was attenuated by satiety (but unaffected by sibutramine) while the hypothalamic and amygdala responses were attenuated by drug but unaffected by satiety. Direct assessment of regional interactions confirmed the significance of this double dissociation. We explored the regional responses in greater detail by determining whether they were predictive of eating behaviour and weight change. We observed that across the different regions, the individual-specific magnitude of drug- and satiety-induced modulation was associated with both variables: the sibutramine-induced modulation of the hypothalamic response was correlated with the drug’s impact on both weight and subsequently-measured ad libitum eating. The satiety-induced modulation of striatal response also correlated with subsequent ad lib eating. These results suggest that hypothalamus and amygdala have roles in the control of food intake that are distinct from those of ventral striatum. Furthermore, they support a regionally-specific effect on brain function through which sibutramine exerts its clinical effect. PMID:20980590

  1. Vision and the hypothalamus.

    Science.gov (United States)

    Trachtman, Joseph N

    2010-02-01

    For nearly 2 millennia, signs of hypothalamic-related vision disorders have been noticed as illustrated by paintings and drawings of that time of undiagnosed Horner's syndrome. It was not until the 1800s, however, that specific connections between the hypothalamus and the vision system were discovered. With a fuller elaboration of the autonomic nervous system in the early to mid 1900s, many more pathways were discovered. The more recently discovered retinohypothalamic tracts show the extent and influence of light stimulation on hypothalamic function and bodily processes. The hypothalamus maintains its myriad connections via neural pathways, such as with the pituitary and pineal glands; the chemical messengers of the peptides, cytokines, and neurotransmitters; and the nitric oxide mechanism. As a result of these connections, the hypothalamus has involvement in many degenerative diseases. A complete feedback mechanism between the eye and hypothalamus is established by the retinohypothalamic tracts and the ciliary nerves innervating the anterior pole of the eye and the retina. A discussion of hypothalamic-related vision disorders includes neurologic syndromes, the lacrimal system, the retina, and ocular inflammation. Tables and figures have been used to aid in the explanation of the many connections and chemicals controlled by the hypothalamus. The understanding of the functions of the hypothalamus will allow the clinician to gain better insight into the many pathologies associated between the vision system and the hypothalamus. In the future, it may be possible that some ocular disease treatments will be via direct action on hypothalamic function. Copyright 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

  2. Autoradiographic studies on nucleic acid synthesis of human gastric cancer cells, 2. Effects of 5-Fluorouracil on nucleic acid synthesis of cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, K [Kobe Univ. (Japan). School of Medicine

    1982-03-01

    Changes in nucleic acid synthesis of gastric cancer cells by oral administration of 5-fluorouracil (5-FU) were evaluated autoradiographically. 1) Average /sup 3/H-thymidine labeling index (TLI) in the administered group (31.8%, n = 13) was a significantly high value compared with that of the control group (22.4%, n = 21). This result is considered to show that the pharmacological effects of 5-FU appeared on the cancer cells by the clinical administration of 5-FU. 2) Increase in TLI of the administered group was also found in the advanced stages. However, the degree of its increase seemed to be higher in the early stages. 3) Average /sup 3/H-uridine labeling index (89.9%) was not different from that (92.7%) of control group.

  3. On coherent optical evaluation of autoradiographs

    International Nuclear Information System (INIS)

    Birkholz, W.; Freyer, K.

    1978-01-01

    The autoradiography imaging process can be described through the imaging equation s(y 1 ,y 2 ) = ∫ a(x 1 ,y 2 )h(y 1 ,y 2 ,x 1 ,x 2 )dx 1 dx 2 where s(y 1 ,y 2 ) in the density distribution of the autoradiograph, a(x 1 ,x 2 ) is the activity distribution over a plane sample and h(y 1 ,y 2 ,x 1 ,x 2 ) transfer fuction of the system. Light transfer through a lens system may be characterized in an analogous way. By application of the Fourier transformation to the imaging equation, the autoradiographic imaging process becomes a filter process with the function H (= Fourier transformer of h). If autoradiographs are imaged through a lens system by means of coherent light the Fourier transform of the autoradiograph is formed in the Fourier plane. Through suitable arrangement of filters in the Fourier plane, systematic imaging errors can be corrected or the autoradiographic imaging be changed. The possibilities of coherent-optical filtration in the evaluation of autoradiographs are considered. (author)

  4. Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone.

    NARCIS (Netherlands)

    Wu, Y.-H.; Zhou, J.-N.; Balesar, R.; Unmehopa, U.; Bao, A.; Jockers, R.; Heerikhuize, J.; Swaab, D.F.

    2006-01-01

    Melatonin is implicated in numerous physiological processes, including circadian rhythms, stress, and reproduction, many of which are mediated by the hypothalamus and pituitary. The physiological actions of melatonin are mainly mediated by melatonin receptors. We here describe the distribution of

  5. Mu opioid receptor binding sites in human brain

    International Nuclear Information System (INIS)

    Pilapil, C.; Welner, S.; Magnan, J.; Zamir, N.; Quirion, R.

    1986-01-01

    Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand [ 3 H]DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of [ 3 H]DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas

  6. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity.

    Science.gov (United States)

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P M; Swaab, Dick F

    2011-10-15

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir) neurons in relation to sex, age, and gender identity in the postmortem brain of 77 subjects. First we compared the InM volume and number of Gal-Ir neurons of 22 males and 22 females in the course of aging. In a second experiment, we compared for the first time the InM volume and the total and Gal-Ir neuron number in 43 subjects with different gender identities: 14 control males (M), 11 control females (F), 10 male-to-female (MtF) transsexual people, and 5 men who were castrated because of prostate cancer (CAS). In the first experiment we found a sex difference in the younger age group ( 45 years. In the second experiment the MtF transsexual group presented an intermediate value for the total InM neuron number and volume that did not seem different in males and females. Because the CAS group did not have total neuron numbers that were different from the intact males, the change in adult circulating testosterone levels does not seem to explain the intermediate values in the MtF group. Organizational and activational hormone effects on the InM are discussed. Copyright © 2011 Wiley-Liss, Inc.

  7. Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer's disease neuropathology

    NARCIS (Netherlands)

    Hestiantoro, Andon; Swaab, Dick F.

    2004-01-01

    The expression of estrogen receptor (ER)alpha and -beta in the infundibular nucleus of the hypothalamus was studied immunocytochemically in 28 control subjects and 14 patients with Alzheimer's disease (AD). A shift was found from more nuclear staining of ERalpha in young female controls to more

  8. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances.

    NARCIS (Netherlands)

    Wang, S.S.; Kamphuis, W.; Huitinga, I.; Zhou, J.N.; Swaab, D.F.

    2008-01-01

    Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors

  9. The possible distortion of autoradiographic results

    International Nuclear Information System (INIS)

    Kozlov, A.A.; Tumanushvili, G.D.

    1980-01-01

    The effect of radioactive labelling (H 3 -thymidine) on the infusorian division is studied. The presented results show that introduction of labelled compounds results in accelerating infusorian cell division v. Thorough inestigation of labelled compound effect with low activity on the parameters of cell division and the search of methods to eliminate distortions able to appear in autoradiographic experiments is expedient [ru

  10. An autoradiographic study of equine hoof growth

    International Nuclear Information System (INIS)

    Pollitt, C.C.

    1990-01-01

    This report introduces an autoradiographic method of studying the growth of entire equine hoof sections. It has the advantage that accurate measurements can be made of changes in the rate of growth before and after treatment such as dietary supplementation with biotin on the development of laminitis

  11. Cytogenetic and autoradiographic investigations in gonadal dysgenesis

    International Nuclear Information System (INIS)

    Baron, J.; Warenik-Szymankiewicz, A.; Medical Academy, Poznan

    1977-01-01

    Cytogenetic analysis in 23 patients with Turner's syndrome and in 33 women with pure gonadal dysgenesis consisted of sex chromatin determination and karyotype studies employing autoradiography in questionable cases. Here autoradiography is used as an indispensable complement to cytogenetic techniques. The labelling behaviour of aberrant chromosomes is described. After treatment of the autoradiographic films for more differentiation in results is employed

  12. Quantitative autoradiographic analysis of estradiol retention by cells in the preoptic area, hypothalamus and amygdala

    International Nuclear Information System (INIS)

    Morrell, J.I.; Krieger, M.S.; Pfaff, D.W.

    1986-01-01

    These experiments were done to compare quantitatively, on a cell-by-cell basis, estradiol retention by cells in the medial preoptic area, arcuate nucleus, ventrolateral subdivision of the ventromedial nucleus, and the caudal half of the medial nucleus of the amygdala. The steroid autoradiograms were prepared from 2 μ sections of brains from overlectomized, adrenalectomized adult female rats that had been infused intravenously with [ 3 H] estradiol (E 2 ) in a regimen which kept circulating hormone concentration at or above proestrus levels for 3-4 h. Even in these brain regions, containing the most dense collections of E 2 -concentrating cells, a maximum of only 27-61% of the cells concentrated E 2 . Therefore, in these regions only a particular subset of the cells retain hormone; other cells in the region do not retain hormone. Frequency distribution histograms of the number of grains per cell versus the number of cells in each region showed a wide range in the amount of E 2 retained per cell, and no modes among E 2 -retaining cells. The data followed a distribution markedly different from that predicted by a simple Poisson distribution, confirming that E 2 -retention does not result from a random, passive process such as diffusion. The overall quantitative characteristics of the frequency distribution histograms were similar across the four brain areas. (orig./MG)

  13. Distribution of neurotensin receptors in the primate hippocampal region: a quantitative autoradiographic study in the monkey and the postmortem human brain

    International Nuclear Information System (INIS)

    Kohler, Christer; Radesater, A.; Chan-Palay, V.

    1987-01-01

    The distribution of [ 3 H]neurotensin ([ 3 H]NT) binding sites in the monkey and the postmortem human brain was studied by using quantitative in vitro receptor autoradiography. Biochemical experiments carried out on tissue sections of the monkey hippocampus showed that the binding of [ 3 H]NT was saturable, reversible and of high specificity. The hippocampal [ 3 H]NT binding was displaced by fragment NT 8-13 but not fragment NT 1-8 of the peptide. The anatomical analysis showed a highly heterogeneous distribution of [ 3 H]NT binding sites within both the monkey and the human hippocampal region. In both species the highest density of [ 3 H]NT binding sites was found in the presubiculum (rank order of binding density: layer 2>6>1>3, 4, 5 in both monkey and man) and the entorhinal area (monkey: layer 4>6>5>1>2>3; human: layer 1=2>5>3). The subiculum and Ammon's horn were relatively poor in [ 3 H]NT binding sites in both species. In the area dentata the highest density of [ 3 H]NT binding sites was found in the hilar region. (author)

  14. Autoradiographic localization of adenosine receptors in rat brain using [3H]cyclohexyladenosine

    International Nuclear Information System (INIS)

    Goodman, R.R.; Synder, S.H.

    1982-01-01

    Adenosine (A1) receptor binding sites have been localized in rat brain by an in vitro light microscopic autoradiographic method. The binding of [ 3 H]N6-cyclohexyladenosine to slide-mounted rat brain tissue sections has the characteristics of A1 receptors. It is saturable with high affinity and has appropriate pharmacology and stereospecificity. The highest densities of adenosine receptors occur in the molecular layer of the cerebellum, the molecular and polymorphic layers of the hippocampus and dentate gyrus, the medial geniculate body, certain thalamic nuclei, and the lateral septum. High densities also are observed in certain layers of the cerebral cortex, the piriform cortex, the caudate-putamen, the nucleus accumbens, and the granule cell layer of the cerebellum. Most white matter areas, as well as certain gray matter areas, such as the hypothalamus, have negligible receptor concentrations. These localizations suggest possible central nervous system sites of action of adenosine

  15. Use of Biopsy Tissue Samples, Incubated In Vitro for Autoradiographic Measurement of Cell Proliferation in Human Tissues; Utilisation de Biopsies Incubees In Vitro pour la Mesure Autoradiographique de la Proliferation Cellulaire de Tissus Humains

    Energy Technology Data Exchange (ETDEWEB)

    Galand, P. [Faculte de Medecine de l' Universite Libre de Bruxelles, Bruxelles (Belgium)

    1970-02-15

    To avoid the radiobiological hazards linked to the use of {sup 3}H-thymidine, several workers have performed in vitro incubations of biopsy material in the presence of this labelled DNA -precursor. Attempts were made to define the proliferative pattern of the tissue from the distribution and intensity of labelling in autoradiographs. However, for true estimation of the cell cycle length, one has to know the S-phase (DNA-synthesis phase) duration, since the labelling index reflects only the part taken by this phase in the whole cell cycle. We chose the ''double-labelling technique'' with two dose levels of {sup 3}H-thymidine, which was developed by Maurer's group. By administering two pulses of the tritiated precursor (a weak dose and a heavy dose) at a given time interval and submitting the treated tissue to the autoradiographic process, one can calculate the S-phase duration(s) after the formula N{sub h}/N{sub w} = S/t. N{sub h} is the number of heavily labelled nuclei (i.e. those nuclei that were engaged in S-phase during the second pulse labelling); N{sub w} is the number of weakly labelled nuclei, corresponding to the cells which left S-phase during the time interval (t) between the two pulse labellings. From the percentage of heavily labelled nuclei in the whole population (L.I.), the generation time (G.T.) is then given by the formula G.T. = S/L.I. x 100. Human rectal and gastric biopsies were submitted to this procedure which, because of its brevity, requires simple survival conditions. Normal and pathologic cases were studied. Endometrial tissue is also currently under study. In parallel, experiments on animal tissues were also performed in order to make a comparison for the same individual between in vitro and in vivo measurements. This latter was realized by the classic method of the wave of labelled mitoses. The following aspects were examined: (1) Proper choice of the dose range, for valid recognition of ''weakly'' and ''heavily'' labelled cells; (2

  16. Autoradiographic study of corrosion of refractories

    International Nuclear Information System (INIS)

    Lisenenkova, S.B.; Kucheryavyi, M.N.; Bursteva, T.A.

    1988-01-01

    A comparative study was made of the character of the interaction between a container-glass melt consisting of sodium calcium silicate and refractories in various furnace sections using an autoradiographic method. Static tests were conducted on specimens of the following refractories: chrome-aluminum-zircon, Bakor 41, corundum, a high alumina refractory, and a refractory based on tin dioxide. The specimens were activated by calcium 45. Autoradiography and photomicrography indicated that an intrinsic feature of all refractories was that calcium from the melt penetrated the refractories along the weak link; for fused-cast refractories, the glass phase; and for sintered refractories, through the binder and cracks

  17. Autoradiographic images in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    Portu, A.; Molinari, A.J.; Schwint, A.; Saint Martin, G.; Thorp, S.; Pozzi, E.C.C.; Curotto, P.

    2013-01-01

    The aim of this work is to summarize the autoradiographic study performed to samples from different protocols of the hamster cheek pouch oral cancer model. The qualitative analysis of histological and autoradiographic images, together with the determination of the boron concentration in the different structures of tumor, premalignant tissue and normal tissue contributed to the knowledge of the microdistribution of boron compounds. Besides, the study led to the optimization of the autoradiography technique applied to BNCT (Boron Neutron Capture Therapy). (author)

  18. Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum

    NARCIS (Netherlands)

    Fletcher, P.C.; Napolitano, A.; Skeggs, A.; Miller, S.R.; Delafont, B.; Cambridge, V.C.; de Wit, S.; Nathan, P.J.; Brooke, A.; O'Rahilly, S.; Farooqi, I.S.; Bullmore, E.T.

    2010-01-01

    We used functional magnetic resonance imaging to explore brain responses to food images in overweight humans, examining independently the impact of a prescan meal ("satiety") and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly

  19. Hide and seek: a comparative autoradiographic in vitro investigation of the adenosine A3 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Haeusler, D.; Fuchshuber, F.; Girschele, F.; Hacker, M.; Wadsak, W.; Mitterhauser, Markus [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Grassinger, L. [University of Applied Sciences Wiener Neustadt, Department of Biomedical Analytics, Wiener Neustadt (Austria); Hoerleinsberger, W.J. [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); University of Vienna, Cognitive Science Research Platform, Vienna (Austria); Hoeftberger, R.; Leisser, I. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Shanab, K.; Spreitzer, H. [University of Vienna, Department of Drug and Natural Product Synthesis, Vienna (Austria); Gerdenitsch, W. [Medical University of Vienna, Institute of Biomedicinal Research, Vienna (Austria)

    2015-05-01

    Since the adenosine A3 receptor (A3R) is considered to be of high clinical importance in the diagnosis and treatment of ischaemic conditions (heart and brain), glaucoma, asthma, arthritis, cancer and inflammation, a suitable and selective A3R PET tracer such as [{sup 18}F]FE rate at SUPPY would be of high clinical value for clinicians as well as patients. A3R was discovered in the late 1990s, but there is still little known regarding its distribution in the CNS and periphery. Hence, in autoradiographic experiments the distribution of A3R in human brain and rat tissues was investigated and the specific binding of the A3R antagonist FE rate at SUPPY and MRS1523 compared. Immunohistochemical staining (IHC) experiments were also performed to validate the autoradiographic findings. For autoradiographic competition experiments human post-mortem brain and rat tissues were incubated with [{sup 125}I]AB-MECA and highly selective compounds to block the other adenosine receptor subtypes. Additionally, IHC was performed with an A3 antibody. Specific A3R binding of MRS1523 and FE rate at SUPPY was found in all rat peripheral tissues examined with the highest amounts in the spleen (44.0 % and 46.4 %), lung (44.5 % and 45.0 %), heart (39.9 % and 42.9 %) and testes (27.4 % and 29.5 %, respectively). Low amounts of A3R were found in rat brain tissues (5.9 % and 5.6 %, respectively) and human brain tissues (thalamus 8.0 % and 9.1 %, putamen 7.8 % and 8.2 %, cerebellum 6.0 % and 7.8 %, hippocampus 5.7 % and 5.6 %, caudate nucleus 4.9 % and 6.4 %, cortex 4.9 % and 6.3 %, respectively). The outcome of the A3 antibody staining experiments complemented the results of the autoradiographic experiments. The presence of A3R protein was verified in central and peripheral tissues by autoradiography and IHC. The specificity and selectivity of FE rate at SUPPY was confirmed by direct comparison with MRS1523, providing further evidence that [{sup 18}F]FE rate at SUPPY may be a suitable A3 PET

  20. Autoradiographic localization of (125I-Tyr4)bombesin-binding sites in rat brain

    International Nuclear Information System (INIS)

    Zarbin, M.A.; Kuhar, M.J.; O'Donohue, T.L.; Wolf, S.S.; Moody, T.W.

    1985-01-01

    The binding of ( 125 I-Tyr 4 )bombesin to rat brain slices was investigated. Radiolabeled (Tyr 4 )bombesin bound with high affinity (K/sub d/ . 4 nM) to a single class of sites (B/sub max/ . 130 fmol/mg of protein); the ratio of specific to nonspecific binding was 6/1. Also, pharmacology studies indicated that the C-terminal of bombesin was important for the high affinity binding activity. Autoradiographic studies indicated that the ( 125 I-Tyr4)bombesin-binding sites were discretely distributed in certain gray but not white matter regions of rat brain. Highest grain densities were present in the olfactory bulb and tubercle, nucleus accumbens, suprachiasmatic and periventricular nuclei of the hypothalamus, central medial thalamic nucleus, medial amygdaloid nucleus, hippocampus, dentate gyrus, subiculum, nucleus of the solitary tract, and substantia gelatinosa. Moderate grain densities were present in the parietal cortex, deep layers of the neocortex, rhinal cortex, caudate putamen, stria terminalis, locus ceruleus, parabrachial nucleus, and facial nucleus. Low grain densities were present in the globus pallidus, lateral thalamus, and midbrain. Negligible grain densities were present in the cerebellum, corpus callosum, and all regions treated with 1 microM unlabeled bombesin. The discrete regional distribution of binding suggests that endogenous bombesin-like peptides may function as important regulatory agents in certain brain loci

  1. The site of action of intrahypothalamic estrogen implants in feminine sexual behavior: an autoradiographic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Davis, P.G.; Krieger, M.S.; Barfield, R.J.; McEwen, B.S.; Pfaff, D.W.

    1982-11-01

    Estrogenic stimulation of the ventromedial hypothalamus is sufficient to prime progesterone-facilitated estrous behavior in ovariectomized rats. To determine precisely the site(s) of estrogenic stimulation and the locus of its priming action on estrous behavior, we used steroid autoradiographic methods to assess the diffusion of (/sup 3/H)estradiol ((/sup 3/H)E/sub 2/) from behaviorally effective implants diluted 1:300 with cholesterol. Ovariectomized rats received (/sup 3/H)E/sub 2/-cholesterol implants aimed at the ventromedial hypothalamic nucleus (VMN). Females were tested twice for feminine sexual behavior after stereotaxic surgery. They received progesterone on the day of behavioral testing. Animals were killed on the day after the second behavior test, cannulae were removed, and the brains were frozen rapidly and processed for autoradiography. Five of eight females with bilateral implants aimed at the VMN exhibited female sexual behavior in at least one of the two tests. Of these, four also showed proceptive behavior. Histological examination of brain sections indicated that behaviorally effective implants were located in, or adjacent to, the central portions of VMN. Implants from nonreceptive animals were located at the extreme anterior or posterior aspects of the VMN. The data collected are consistent with the view that estrogen acts within a sharply defined region of the VMN to prime estrons behavior.

  2. The site of action of intrahypothalamic estrogen implants in feminine sexual behavior: an autoradiographic analysis

    International Nuclear Information System (INIS)

    Davis, P.G.; Krieger, M.S.; Barfield, R.J.; McEwen, B.S.; Pfaff, D.W.

    1982-01-01

    Estrogenic stimulation of the ventromedial hypothalamus is sufficient to prime progesterone-facilitated estrous behavior in ovariectomized rats. To determine precisely the site(s) of estrogenic stimulation and the locus of its priming action on estrous behavior, we used steroid autoradiographic methods to assess the diffusion of [ 3 H]estradiol ([ 3 H]E 2 ) from behaviorally effective implants diluted 1:300 with cholesterol. Ovariectomized rats received [ 3 H]E 2 -cholesterol implants aimed at the ventromedial hypothalamic nucleus (VMN). Females were tested twice for feminine sexual behavior after stereotaxic surgery. They received progesterone on the day of behavioral testing. Animals were killed on the day after the second behavior test, cannulae were removed, and the brains were frozen rapidly and processed for autoradiography. Five of eight females with bilateral implants aimed at the VMN exhibited female sexual behavior in at least one of the two tests. Of these, four also showed proceptive behavior. Histological examination of brain sections indicated that behaviorally effective implants were located in, or adjacent to, the central portions of VMN. Implants from nonreceptive animals were located at the extreme anterior or posterior aspects of the VMN. The data collected are consistent with the view that estrogen acts within a sharply defined region of the VMN to prime estrons behavior

  3. The autoradiographic localization of paraquat in the lung

    International Nuclear Information System (INIS)

    Webb, D.B.

    1980-01-01

    Paraquat poisoning in mammals results in a characteristic lung lesion manifested principally as progressive pulmonary fibrosis. Paraquat is actively concentrated into the lung but the site of uptake remains undefined. A method is described for the autoradiographic localization of paraquat in rats. Preliminary evidence for the site of uptake implicates the bronchiol. (author)

  4. Some remarks on the evaluation of autoradiographs by means of microdensitometer ''Scanding 3''

    International Nuclear Information System (INIS)

    Mysak, F.; Spunda, J.

    1980-01-01

    Some factors, which influence the evaluation of autoradiographs by means of microdensitometer ''Scanding 3'' are described. The effect of pixel's area (area of picture element) used for digitalization of autoradiographs was studied. Experiments were carried out to explain the phenomena which are connected with scanning of fine details of structure. Attention is drawn to the influence of quantification of the optical density during digitalization of an autoradiograph on its evaluation. (author)

  5. Autoradiographic studies of oleilanilide-3H distribution in rat tissues

    International Nuclear Information System (INIS)

    Negro Alvarez, M.J.; Saez Angulo, R.M.

    1987-01-01

    In this work the possibility that oleilanilides are involved in the pathgenesis of ''toxic syndrome'' is studied. Oleilanilide- 3 H labelled in the anilidi aromatic ring has been used to determine the distribution, localization and incorporation of that compound in several tissues of rats. Liquid scintillation counting for quantitative evaluation of the total radioactivity accumulated in the tissues, as well as autoradiographic techniques have been employed as analytical procedures. Results obtained from measurement of total radioactivity have shown accumulation of oleilanilide or its metabolites in all the studied tissues, mainly in the liver. No specific radioactivity localization has been detected by autoradiographic techniques, being the labelled molecules distributed in cytaplasm and cell interstice. (Author)

  6. Autoradiographic studies of actinide sorption in groundwater systems

    International Nuclear Information System (INIS)

    O'Kelley, G.D.; Beall, G.W.; Allard, B.

    1980-01-01

    Autoradiography is a convenient and sensitive technique for the study of spacial distributions of alpha radioactive nuclides on slabs of rock or on other planar surfaces. The autoradiographic camera contains an arrangement for placing in firm contact Polaroid sheet film, a plastic scintillator screen, and the radioactive face of the specimen. As an example of the use of the autoradiographic method, a series of sorption experiments were carried out in which synthetic groundwater solutions of americium, neptunium, uranium, and plutonium were contacted with Climax Stock granite under aerated and anoxic conditions at pH 8 to 9. The sorption observed at specific mineral sites was correlated with data on sorption of these actinides on pure minerals

  7. A new approach to the autoradiographic study of proliferating lymphocytes

    International Nuclear Information System (INIS)

    Zweiman, B.; Lisak, R.P.

    1978-01-01

    An adaptation of a cell filtration method for the autoradiographic study of cultured lymphocytes has been developed. The percentages of labelled cells are very similar in the filtered cell population to those obtained from replicate cultures processed by centrifugation. The filter method permitted a higher recovery of cells from small numbers in culture with better cytological detail than seen when cells were washed by repeated centrifugation, then suspended and smeared. (author)

  8. Application of autoradiographic methods for contaminant distribution studies in soils

    International Nuclear Information System (INIS)

    Povetko, O.G.; Higley, K.A.

    2000-01-01

    In order to determine physical location of contaminants in soil, solidified soil 'thin' sections, which preserve the undisturbed structural characteristics of the original soil, were prepared. This paper describes an application of different autoradiographic methods to identify the distribution of selected nuclides along key structural features of sample soils and sizes of 'hot particles' of contaminant. These autoradiographic methods included contact autoradiography using CR-39 (Homalite Plastics) plastic alpha track detectors and neutron-induced autoradiography that produced fission fragment tracks in Lexan (Thrust Industries, Inc.) plastic detectors. Intact soil samples containing weapons-grade plutonium from Rocky Flats Environmental Test Site and control samples from outside the site location were used in thin soil section preparation. Distribution of particles of actinides was observed and analyzed through the soil section depth profile from the surface to the 15-cm depth. The combination of two autoradiographic methods allowed to distinguish alpha- emitting particles of natural U, 239+240 Pu and non-fissile alpha-emitters. Locations of 990 alpha 'stars' caused by 239+240 Pu and 241 Am 'hot particles' were recorded, particles were sized, their size-frequency, depth and activity distributions were analyzed. Several large colloidal conglomerates of 239+240 Pu and 241 Am 'hot particles' were found in soil profile. Their alpha and fission fragment 'star' images were micro photographed. (author)

  9. Autoradiographic localization of 3H-paroxetine-labeled serotonin uptake sites in rat brain

    International Nuclear Information System (INIS)

    De Souza, E.B.; Kuyatt, B.L.

    1987-01-01

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin

  10. Adrenergic innervation of the rat hypothalamus

    NARCIS (Netherlands)

    Palkovits, M.; Mezey, E.; Záborszky, L.; Feminger, A.; Versteeg, D.H.G.; Wijnen, H.J.L.M.; Jong, Wybren de; Fekete, M.I.K.; Herman, J.P.; Kanyicska, B.

    The adrenergic innervation of the hypothalamus was studied by measuring hypothalamic adrenaline levels following surgical transection of the lower brain stem or electrolytic lesion of the medullary adrenaline-containing cell groups. The adrenaline levels in some hypothalamic nuclei and in the median

  11. The hypothalamus at the crossroads of psychopathology and neurosurgery.

    Science.gov (United States)

    Barbosa, Daniel A N; de Oliveira-Souza, Ricardo; Monte Santo, Felipe; de Oliveira Faria, Ana Carolina; Gorgulho, Alessandra A; De Salles, Antonio A F

    2017-09-01

    The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the

  12. Distribution of seratonin-1A receptors in the monkey and the postmortem human hippocampal region. A quantitative autoradiographic study using the selective agonist (3H)8-PH-DPAT

    International Nuclear Information System (INIS)

    Koehler, Christer; Radesaeter, A.C.; Lang, Walter; Chan-Palay, Victoria

    1986-01-01

    Serotonin-1A receptors were visualized and their anatomical distribution mapped within the monkey and the human hippocampus by using in vitro receptor autoradiography of the selective agonist ( 3 H)8-OH-N, N-dipropyl-2-aminotetralin (( 3 H)8-OH-DPAT). The results show high densities of serotonin-1A receptors hetergeneously distributed in different subfields and layers of the monkey and the human hippocampal region. High densities are found in the molecular layer of area dentata, all layers of regio superior and the subiculum, parasubiculum, and layers 2, and 4 through 6 of the entorhinal area. In the human hippocampus, a distinct band of ( 3 H)8-OH-DPAT binding sites is present in the subgranular zone of the area dentata. The similar anatomical distribution of ( 3 H)8-OH-DPAT binding sites in the monkey and the human hippocampal region suggests that the serotonin-1A receptor is phylogenetically well preserved and indicates that this receptor may mediate action(s) of serotonin in the primate, including the human hippocampal region. (author)

  13. [{sup 125}I]{beta}-CIT-FE and [{sup 125}I]{beta}-CIT-FP are superior to [{sup 125}I]{beta}-CIT for dopamine transporter visualization: Autoradiographic evaluation in the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Ilonka; Hall, Haakan; Halldin, Christer; Swahn, Carl-Gunnar; Farde, Lars; Sedvall, Goeran

    1997-10-01

    The binding of the three dopamine transporter radioligands ([{sup 125}I]{beta}-CIT, [{sup 125}I]{beta}-CIT-FE, and [{sup 125}I]{beta}-CIT-FP) was studied using whole-hemisphere autoradiography on postmortem human brains. The autoradiograms revealed an intense and homogeneous labeling of the nucleus caudatus and putamen but also to varying extent to serotonergic and noradrenergic transporters of neocortex and thalamus. The order of specificity estimated (striatum over neocortex ratios) was {beta}-CIT-FP > {beta}-CIT-FE >> {beta}-CIT, suggesting that {beta}-CIT-FE and {beta}-CIT-FP should be preferred for in vivo studies of the dopamine transporter in the human brain.

  14. MicroRNAs in the Hypothalamus

    DEFF Research Database (Denmark)

    Meister, Björn; Herzer, Silke; Silahtaroglu, Asli

    2013-01-01

    MicroRNAs (miRNAs) are short (∼22 nucleotides) non-coding ribonucleic acid (RNA) molecules that negatively regulate the expression of protein-coding genes. Posttranscriptional silencing of target genes by miRNA is initiated by binding to the 3'-untranslated regions of target mRNAs, resulting...... of the hypothalamus and miRNAs have recently been shown to be important regulators of hypothalamic control functions. The aim of this review is to summarize some of the current knowledge regarding the expression and role of miRNAs in the hypothalamus.......RNA molecules are abundantly expressed in tissue-specific and regional patterns and have been suggested as potential biomarkers, disease modulators and drug targets. The central nervous system is a prominent site of miRNA expression. Within the brain, several miRNAs are expressed and/or enriched in the region...

  15. The anterior hypothalamus in cluster headache.

    Science.gov (United States)

    Arkink, Enrico B; Schmitz, Nicole; Schoonman, Guus G; van Vliet, Jorine A; Haan, Joost; van Buchem, Mark A; Ferrari, Michel D; Kruit, Mark C

    2017-10-01

    Objective To evaluate the presence, localization, and specificity of structural hypothalamic and whole brain changes in cluster headache and chronic paroxysmal hemicrania (CPH). Methods We compared T1-weighted magnetic resonance images of subjects with cluster headache (episodic n = 24; chronic n = 23; probable n = 14), CPH ( n = 9), migraine (with aura n = 14; without aura n = 19), and no headache ( n = 48). We applied whole brain voxel-based morphometry (VBM) using two complementary methods to analyze structural changes in the hypothalamus: region-of-interest analyses in whole brain VBM, and manual segmentation of the hypothalamus to calculate volumes. We used both conservative VBM thresholds, correcting for multiple comparisons, and less conservative thresholds for exploratory purposes. Results Using region-of-interest VBM analyses mirrored to the headache side, we found enlargement ( p cluster headache compared to controls, and in all participants with episodic or chronic cluster headache taken together compared to migraineurs. After manual segmentation, hypothalamic volume (mean±SD) was larger ( p cluster headache compared to controls (1.72 ± 0.15 ml) and migraineurs (1.68 ± 0.19 ml). Similar but non-significant trends were observed for participants with probable cluster headache (1.82 ± 0.19 ml; p = 0.07) and CPH (1.79 ± 0.20 ml; p = 0.15). Increased hypothalamic volume was primarily explained by bilateral enlargement of the anterior hypothalamus. Exploratory whole brain VBM analyses showed widespread changes in pain-modulating areas in all subjects with headache. Interpretation The anterior hypothalamus is enlarged in episodic and chronic cluster headache and possibly also in probable cluster headache or CPH, but not in migraine.

  16. Proteomic profiling of the rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Pedroso Amanda P

    2012-04-01

    Full Text Available Abstract Background The hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE profile of rat hypothalamus proteins. Results As a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development. Conclusion The present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.

  17. Autoradiographic study of the brain of the brambling (Fringilla montifringilla L.) after 3H-testosterone injection

    International Nuclear Information System (INIS)

    Luecke, J.; Haase, E.

    1980-01-01

    The topographic distribution of 3 H-testosterone and/or its metabolites in brains of brablings (Fringilla montifringilla L.) was studied autoradiographically and the intensity of labelling was estimated semiquantitatively. The highest accumulation of radioactivity was found in nuclei of the preoptic region and the hypothalamus. Cells of the nucleus preopticus medialis. Nucleus paraventricularis magnocellularis and nucleus lateralis hypothalami posterioris showed medium or high intensity labelling, while cells of the nucleus preopticus paraventricularis magnocellularis, nucleus hypothalamicus anterior medialis, nucleus hypothalamicus posterior medialis, and the infundibular area contained low or medium concentrations of radioactivity. The role of these nuclei in the gonadal feedback on the hypothalamo-hypophyseal system, in the control of the annual reproductive cycle and as effective sites of testosterone on sexual behaviour are discussed. Moderate accumulations of radioactivity were also observed in the hyperstriatum ventrale of the telencephalon, the nucleus intercollicularis of the mesencephalon and the nucleus nervi hypoglossi of the medulla. These structures are known to influence bird song and other vocalisations. Low labelled cells were found in the periventricular zone of the neostriatum, in the lateral septum, and more irregularly in other areas. The pattern of distribution was similar to that in other birds. (author)

  18. Autoradiographic methods for studying marked volatile substances (1961)

    International Nuclear Information System (INIS)

    Cohen, Y.; Wepierre, J.

    1961-01-01

    The autoradiographic methods for animals used up to the present do not make it possible to localise exactly the distribution of marked volatile molecules. The Ullberg method (1954) which we have modified (Cohen, Delassue, 1959) involves cold desiccant. The method due to Pellerin (1957) avoids this desiccant but the histological comparison of the autoradiography with the biological document itself is difficult, if not impossible. Nevertheless, we have adopted certain points in the two methods and propose the following technique for the autoradiographic study of marked volatile molecules: 1- The surface of the frozen sample to be studied is prepared using a freezing microtome. 2- The last section, which is 20 μ thick and whose histological elements are parallel to those of the block, is dried by cooling and is used as the biological reference document for the autoradiography obtained, as is indicated in 3; 3- The radiography films are applied to the frozen block at -30 deg. C. The autoradiographs correspond to the radioactivity of the volatile molecule and of its non-volatile degradation products. 4- The radiographic film is also applied to the 20 μ section previously dried at -20 deg. C. This autoradiography corresponds to the radioactivity of the non-volatile degradation products of the molecule. 5- We confirmed the absence of diffusion of the volatile molecule and of pseudo-radiographic effects (photochemical and others). This method, which has enabled us to study the distribution of a carbide, para-cymene (C 14 ) 7, macroscopically in the case of a whole mouse and microscopically on the skin of a dog, can find general applications. (authors) [fr

  19. Autoradiographic localization of benzomorphan binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Crain, B.J.; Kwenjen Chang; McNamara, J.O.; Valdes, F.

    1985-07-17

    The benzomorphan subpopulation of opiate binding sites was labeled by (TH)diprenorphine in the presence of unlabeled ligands selected to quench and delta opiate binding sites. The distribution of benzomorphan binding sites was then localized autoradiographically. The distribution differs from the distributions of , delta and kappa opiate binding and is quite similar to the distribution of US -endorphin immunoreactivity. These observations support the hypothesis, based on biochemical studies in brain membranes, that benzomorphan binding sites may represent the ligand recognition sites of putative epsilon receptors. (Auth.). 34 refs.; 3 figs.

  20. Autoradiographical investigations of the proliferation of gynaecological carcinomas

    International Nuclear Information System (INIS)

    Wehweck, H.

    1981-01-01

    23 biopsies and operation preparations of gynaecological tumours were examined autoradiographically: 8 with an external short-time preirradiation of up to 750 R, one with a curative radiotherapy 1 1/2 years ago. Besides the determination of quantitative parameters of growth kinetics another main concern was to find out the interdependence between the proliferation behaviour of the tumour cells and the histological differentiation of the tumour parenchyma and the topographical location of the malignant cells in the tissue. Possible effects of a previous radiotherapy on the cell proliferation are discussed. (orig./MG) [de

  1. Autoradiographic analysis of the in vivo distribution of 3H-imipramine and 3H-desipramine in brain: Comparison to in vitro binding patterns

    International Nuclear Information System (INIS)

    Duncan, G.E.; Paul, I.A.; Fassberg, J.B.; Powell, K.R.; Stumpf, W.E.; Breese, G.R.

    1991-01-01

    Using high resolution autoradiographic techniques, the distribution of radioactivity in forebrain and brainstem was assessed after 4 injection of 3H-impramine or 3H-desipramine. Results were compared with regional binding of the drugs to brain sections in vitro. Similar topographic binding of 3H-imipramine and 3H-desipramine was observed in vitro among brain regions, except in the paraventricular nucleus of the hypothalamus and locus coeruleus, where binding was greater for 3H-desipramine. For both 3H-desipramine and 3H-imipramine, some brain regions that exhibited high binding in vitro also showed high accumulation after in vivo injection. However, certain regions that contained high densities of binding sites for the antidepressant drugs as measured by in vitro binding showed very low accumulation of radioactivity after in vivo treatment. Such regions included the dentate gyrus of the hippocampus, layer 1 of piriform cortex, caudate-putamen, pontine and midbrain central gray, and cerebellar granular layer. Compared to in vitro binding of the drugs, the distribution of imipramine and desipramine in vivo appears more anatomically selective. For imipramine, primary sites of action in vivo, as indicated by the topographic distribution in brain, appear to be the locus coeruleus, hippocampus, lateral septal nucleus, and amygdala. For desipramine, the greatest accumulation in vivo was found in the locus coeruleus, paraventricular nucleus of the hypothalamus, and anterior thalamic nuclei

  2. Hypothalamic projections to the ventral medulla oblongata in the rat, with special reference to the nucleus raphe pallidus: a study using autoradiographic and HRP techniques

    Energy Technology Data Exchange (ETDEWEB)

    Hosoya, Yasuhiko

    1985-10-07

    Hypothalamic descending projections to the medullary ventral surface were studied autoradiographically in the rat. A small amount of (/sup 3/H)leucine was injected unilaterally into various parts of the hypothalamus by air pressure. Abundant and characteristic terminal labelings were observed bilaterally in the nucleus raphe pallidus, the ventral surface to the pyramidal tract and the nucleus interfascicularis hypoglossi, after injections into the dorsal posterior hypothalamic area caudal to the paraventricular hypothalamic nucleus. Conspicuous, but less numerous labelings were observed in the nucleus raphe obscurus and the ipsilateral raphe magnus. After an injection of (/sup 3/H)leucine into the hypothalamus and injections of horseradish peroxidase (HRP) into the spinal cord in the same animal, silver grains were densely distributed around HRP-labeled neurons in the nucleus raphe pallidus including the nucleus interfascicularis hypoglossi. The present results suggest that the dorsal posterior hypothalamic area projects directly to the spinal-projecting neurons of the nucleus raphe pallidus. 53 refs.; 9 figs.

  3. Electron histochemical and autoradiographic studies of vascular smooth muscle cell

    International Nuclear Information System (INIS)

    Kameyama, Kohji; Aida, Takeo; Asano, Goro

    1982-01-01

    The authors have studied the vascular smooth muscle cell in the aorta and the arteries of brain, heart in autopsied cases, cholesterol fed rabbits and canine through electron histochemical and autoradiographic methods, using 3 H-proline and 3 H-thymidine. The vascular changes are variable presumably due to the functional and morphological difference of vessels. Aging, pathological condition and physiological requirement induce the disturbances of vascular functions as contractility. According to various pathological conditions, the smooth muscle cell altered their shape, surface properties and arrangement of subcellular organelles including changes in number. The morphological features of arteries during aging is characterized by the thickening of endothelium and media. Decreasing cellularity and increasing collagen contents in media. The autoradiographic and histochemical observations using periodic acid methenamine silver (PAM) and ruthenium red stains demonstrated that the smooth muscle cell is a connective tissue synthetic cell. The PAM impregnation have proved that the small bundle of microfilaments become associated with small conglomerate of collagen and elastic fibers. Cytochemical examination will provide sufficient evidence to establish the contribution of subcellular structure. The acid phosphatase play an important role in vascular disease and they are directly involved in cellular lipid metabolism in cholesterol fed animals, and the activity of Na-K ATPase on the plasma membrane may contribute to the regulation of vascular blood flow and vasospasms. Direct injury and subsequent abnormal contraction of smooth muscle cell may initiate increased permeability of plasma protein and lipid in the media layer and eventually may developed and enhance arteriosclerosis. (author)

  4. The autoradiographic observation of neutron activated plant samples

    International Nuclear Information System (INIS)

    Koyama, Motoko; Tanizaki, Yoshiyuki

    2003-01-01

    Imaging Plate (IP) is a radiography apparatus of applying photostimulable luminescence. IP has some advantages in comparison with X-ray film, for example, high sensitivity, wide latitude and high fidelity for radiations. The high sensitivity of IP makes it possible to observe the distribution of short-lived nuclides. We obtained autoradiographs of Azuki bean cuttings. In the basal region of Azuki bean cuttings, the intensity of autoradiographs of indole acetic acid (IAA)-treated samples were higher than that of water- and Gibbereline(GA)-treated ones. The high intensity parts of IAA-treated cuttings were extended upwards. The high intensive imaging of basal region treated in IAA indicated that high elemental concentrations were in existence for adventitious root formations. The measurement results by γ-ray spectrometry showed that the Ca content in the Azuki bean cuttings basal region increased in IAA treatment. It seems that the cell division for adventitious root formation needs Ca. In Azuki bean epicotyls, Ca content showed an increase to basal region, though Mg content increased to upper region. (author)

  5. Autoradiographic study of the permeability characteristics of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Kingham, J G.C.; Baker, J H; Loehry, C A [Royal Victoria Hospital, Bournemouth (UK)

    1978-02-01

    This autoradiographic study demonstrates the distribution of a range of small solutes and macromolecules in the mucosa of the guinea-pig small intestine after intracardiac injection. The substances investigated were: /sup 14/C-urea, /sup 3/H-mannose, /sup 3/H-inulin, and /sup 125/I polyvinylpyrrolidone (PVP). Small bowel biopsies were taken at intervals from one to 60 minutes after injection and the tissues processed for autoradiography. Light microscopic examination of the autoradiographs showed that the compartmental distribution depended on the molecular size of the substances being studied. Urea and mannose, as small solutes, were uniformly distributed throughout the intravascular, extravascular, and epithelial compartments. Inulin was evenly distributed in the vessel lumen and extravascular space but there was a considerable drop in concentration in the epithelium. PVP exhibited the most marked gradients, the concentration being greatest in the vascular lumina, lower in the extravascular space, least in the epithelium. Thus there appear to be two barriers to macromolecular passage which are freely permeable to small solutes: the capillary wall and the epithelium. At a light microscopical level it was not possible to observe whether the limiting membrane of each of these barriers is the cell plasmalemmal membrane or the basement membrane. The selectivity of the epithelial barrier was greater than that of the capillary barrier.

  6. Autoradiographic study of nuclear protein acetylation during Locust spermiogenesis

    International Nuclear Information System (INIS)

    Bouvier, D.; Chevaillier, P.

    1975-01-01

    Autoradiographic studies, at the light and electron microscope level, demonstrate that spermatid nuclei of the Locust Locusta migratoria incorporate 3 H-acetate, especially during the first stages of spermiogenesis. The highest level of acetate incorporation is observed during stage II of spermiogenesis. During this stage and the following, the spermatid nucleus undergoes a number of structural and chemical modifications: chromatin decondenses and somatic histones are progressively replaced by newly synthesized arginine-rich proteins. Therefore, the higher degree of acetylation of nuclear components coincides with chromatin decondensation and precedes the protein transition occurring in later stages. Cytochemical and autoradiographic tests have been realized so as to localize 3 H-acetate in the nuclear components. Trichloracetic acid was used at various concentrations: the action of hydrochloric acid, pronase and DNase was also tested. The results support the idea that proteins, and among them histones, are the only nuclear components to be acetylated during spermiogenesis. Thus, histone acetylation seems to play an important role in modulating histone-DNA interactions and allowing histone replacement [fr

  7. Changes in hypothalamus in continuously irradiated sheep

    International Nuclear Information System (INIS)

    Arendarcik, J.; Stanikova, A.; Rajtova, V.; Molnarova, M.

    1983-01-01

    Neurosecretion, PAS-positive mucopolysaccharides and the Nissl substance were studied in the neurons of the rostral, medial and caudal hypothalamus of continuously irradiated ewes. The study was performed on 21 ewes of the Slovak Merino breed of a live weight of 34 kg. The animals were in the period of physiological anoestrus and their age was two to three years. The first group of six ewes was the control. The second group included 15 sheep irradiated with a total dose of 6.7 Gy (700 R) for seven days. Co 60 was used as the source of irradiation. The animals of this group were killed seven days following treatment. The ewes in the third group were left for the study of mortality. The brains were perfused with 2% buffered paraformaldehyde immediately after the bleeding of the sheep; then the brains were removed from the skulls and fixed in buffered picroformol. Paraffin slices were stained with haematoxylin-eosine, aldehyde-fuchsine and alcian blue for neurosecretion, by the PAS reaction for mucopolysaccharides and with cresyl violet for the Nissl substance. It was found that irradiation of the whole body inhibited the activity of neurosecretory cells in the rostral and medial hypothalamus, thus reducing neurosecretion. These regions also showed a reduced activity of the PAS reaction used for the demonstration of mucopolysaccharides. The observed changes also included damage of the endothelium of blood vessels with the occurrence of erythrocyte extravasates and with haemorrhages. In this way, the trophism of neurosecretory cells was affected, which is ascribed to the decrease in the amount of neurosecretory material. In the caudal hypothalamus, neurosecretion and PAS-positivity were slightly stimulated by irradiation. The Nissl substance disappeared as a result of irradiation. (author)

  8. Automated analysis of autoradiographic grains density with scanning microspectrophotometer

    International Nuclear Information System (INIS)

    Han Pingrong

    1988-01-01

    The mouse ascites tumour cells were used as the specimen, and 3 H-thymidine was used as the tracer. The smears were treated without staining or with Eosin or Giemsa-Wright staining. The automatic analysis of autoradiographic silver grains was performed with UNIVAR-MSPM. The relationship between integrated optical density (IOD) and silver grain density (SGD) in cell nuclei was studied. The results showed that the IOD could reflect the SGD basically, the correlation coefficients being 0.922, 0.9118 and 0.6218. Since the G-W stained cell nuclei appeared blue, their IOD was influenced strongly, whereas the Eosin stained cell nuclei appeared light red, their IOD was influenced only slightly. The latter was recommended. This method could be used for studying the DNA synthesis and cell proliferating kinetics

  9. Site of iodination in hyperplastic thyroid glands deduced from autoradiographs

    International Nuclear Information System (INIS)

    Wollman, S.H.; Ekholm, R.

    1981-01-01

    We have tried to ascertain the site of iodination in the chronically stimulated, hyperplastic thyroid gland of rats. Rats were fed propylthiouracil in a commercial rat diet for 10 days. Then the diet was changed to a low iodine diet for 5 days. To label the gland, 10 mCi of 125I-iodide was injected into the left heart ventricle. Ten seconds later the animal was perfused through the left ventricle with a fixative solution containing a goitrogen to block further iodination, and stable iodide to help extract uncombined radioiodide. Electron microscopic autoradiographs prepared from the fixed thyroids show strong labeling over the lumen of the follicle and no consistent labeling of any other site or organelle. We conclude that the site of iodination in the chronically stimulated, hyperplastic thyroid is the follicular lumen, i.e. the same as that in the normal gland

  10. Autoradiographic analysis of protein regeneration in striated skeleton muscle

    International Nuclear Information System (INIS)

    Dadoune, J.P.

    1977-01-01

    An autoradiographic study was conducted of protein regeneration in striated muscles aimed at clarifying the contradictions in the literature: while some authors hold that the regeneration rate is identical for all types of myofibril proteins and the myofibril is thus regenerated as a whole, others claim that the regeneration rate differs depending on the type of the myofibril protein. Tritium-labelled leucine incorporation experiments showed the existence of at least 2 pools of newly formed proteins in striated muscles in both adult and young animals. One pool is regenerated in 1 to 2 weeks, the other roughly in a month. The regeneration of proteins is initially more significant in red fibres; thus the rate of myofibril protein regeneration is not uniform. In adult animals regeneration seems to be slower in filaments than in the sarcoplasm and in the mitochondria. (A.K.)

  11. ANF and exocrine pancreas: ultrastructural autoradiographic localization in acinar cells

    International Nuclear Information System (INIS)

    Chabot, J.G.; Morel, G.; Belles-Isles, M.; Jeandel, L.; Heisler, S.

    1988-01-01

    Atrial natriuretic factor (ANF) binding sites have been recently demonstrated to be present in exocrine pancreas by an in vitro autoradiographic approach. An autoradiographic study was carried out to identify the exocrine cells containing ANF binding sites and to monitor the fate of 125 I-labeled ANF in acinar cells after removal of pancreas at specific time intervals (1-30 min) after intravenous administration. At the light microscopic level, silver grains were found over acinar and centroacinar cells. Concomitant injection of an excess of unlabeled ANF inhibited the binding of labeled peptide by approximately 60%. At the electron microscopic level, the time-course study in acinar cells has revealed that of the cell compartments examined, plasma membrane, Golgi apparatus, mitochondria, and zymogen granules, the nucleus had distinct labeling patterns. Plasma membrane was maximally labeled 1 and 2 min after injection with 125 I-ANF. Golgi apparatus was significantly labeled from 2 to 30 min after injection, mitochondria from 1 to 30 min after injection, zymogen granules at 1 and 15 min, and the nucleus only at 30 min. The lysosomal compartment was not labeled during the 30-min observation period. These results suggest that after binding to the plasma membrane, ANF is rapidly internalized and distributed to the intracellular organelles as a function of time. Labeling of the zymogen granules suggests that they may bind ANF and that the atrial peptide may be secreted by acinar cells. The significance of association of radioactivity with mitochondria and nuclei remains to be elucidated but may represent intracellular sites of action of ANF complementary to those on plasma membranes

  12. Autoradiographic changes in the kidney of the whole-body sublethally x-ray irradiated rat

    Energy Technology Data Exchange (ETDEWEB)

    Olinic, A; Uray, Z

    1977-01-01

    203Hg-hydroxymersalyl uptake/gram of kidney (HU), renal autoradiographic and histologic aspect after 800 R x-ray whole-body rat irradiation was studied. Twenty-four to seventy-two hours after irradiation, HU increased, while tubular autoradiographic granularity decreased. Their return to the control levels occurred gradually within two weeks. The relations of these findings to the early circulatory and dystrophic changes, as well as to the subsequent postirradiation restoring renal process are discussed.

  13. Quantitative autoradiographic characterization of GA-BAB receptors in mammalian central nervous system

    International Nuclear Information System (INIS)

    Chu, D.Chin-Mei.

    1989-01-01

    The inhibitory effects of the amino acid neurotransmitter γ-aminobutyric acid (GABA) within the nervous system appear to be mediated through two distinct classes of receptors: GABA A and GABA B receptors. A quantitative autoradiographic method with 3 H-GABA was developed to examine the hypotheses that GABA A and GABA B sites have distinct anatomical distributions, pharmacologic properties, and synaptic localizations within the rodent nervous system. The method was also applied to a comparative study of these receptors in postmortem human brain from individuals afflicted with Alzheimer's disease and those without neurologic disease. The results indicated that GABA B receptors occur in fewer numbers and have a lower affinity for GABA than GABA A receptors in both rodent and human brain. Within rodent brain, the distribution of these two receptor populations were clearly distinct. GABA B receptors were enriched in the medial habenula, interpeduncular nucleus, cerebellar molecular layer and olfactory glomerular layer. After selective lesions of postsynaptic neurons of the corticostriatal and perforant pathway, both GABA B and GABA A receptors were significantly decreased in number. Lesions of the presynaptic limbs of the perforant but not the corticostriatal pathway resulted in upregulation of both GABA receptors in the area of innervation. GABA B receptors were also upregulated in CA3 dendritic regions after destruction of dentate granule neurons

  14. Pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes of rats with mammary gland cancer induced by N-methyl nitrosourea.

    Science.gov (United States)

    Carrera, M P; Ramírez-Expósito, M J; Valenzuela, M T; García, M J; Mayas, M D; Arias de Saavedra, J M; Sánchez, R; Pérez, M C; Martínez-Martos, J M

    2005-02-01

    Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

  15. Some morphometric and radio-isotopic studies of the early post-natal development of the hypothalamus of the normal and androgenized rat

    International Nuclear Information System (INIS)

    Martyn, C.N.

    1979-01-01

    Female rats given a single injection of testosterone propionate (TP) in the first few days of post-natal life exhibit post-pubertally, persistent vaginal oestrous, sterility, disordered secretion of gonadotrophins and modified patterns of sexual behaviour. The effects of TP on the incorporation of 14 C-uridine in the CNS of 5 and 61/2 day old litter mate triads consisting of male, female and TP treated female rats were investigated. Low resolution autoradiographs of serial sections of brain were prepared and analysed. A sexual dimorphism in cell nuclear size was found in the suprachiasmatic, arcuate and paraventricular nuclei of the hypothalamus. TP treatment resulted in an increase in nuclear size towards the male pattern in the latter two areas. A decrease in cell nuclear size was found in the ventromedial and suprachiasmatic nuclei. Neither sex differences nor changes following TP injection were detected in rate of incorporation of 14 C-uridine in any areas of the brain, although a significant (p<0.02) reduction in uridine incorporation in the adrenal of the female animal 24 hours after TP injection was demonstrated. The results suggested an immediate direct action of TP on the hypothalamus and peripheral tissues of the neonatal rat. (author)

  16. Autoradiographic study of actinide sorption on climax stock granite

    International Nuclear Information System (INIS)

    Beall, G.W.; O'Kelley, G.D.; Allard, B.

    1980-06-01

    An autoradiographic technique that employed an arrangement for placing in firm contact Polaroid sheet film, a scintillator screen, and the radioactive face of a specimen was applied to a study of the sorption of americium, neptunium, plutonium, and uranium on Climax Stock granite under varying conditions of pH and Eh. Qualitative agreement was found between the sorption of americium on crushed, pure minerals and on the minerals comprising the specimen of Climax Stock granite. The observations also supported a mechanism for reduction of Np(V) to Np(IV) and Pu(VI) to Pu(IV) by Fe(II)-containing minerals. There was no evidence for reduction of U(VI) by the Fe(II)-containing minerals, although the uranium, assumed to be present as UO 2 2+ , appeared to be the only actinide species to exhibit sorption by a simple, cation-exchange mechanism at particular mineral sites. Some implications of these results for nuclear waste isolation are discussed briefly

  17. Neurogenesis in spinal cord of mouse: an autoradiographic analysis

    International Nuclear Information System (INIS)

    Nornes, H.O.; Carry, M.

    1978-01-01

    An autoradiographic analysis of the time and sites of origin, and the migration and setting patterns of neurons was made in the spinal cord of the mouse. The neurons originated on days 10-15 of gestation with temporal gradients along the ventrodorsal and rostrocaudal axes. The motor neurons originated on days 10-11 of gestation; the neurons in the intermediate gray region originated on days 11-14 of gestation; the neurons of the head of the dorsal horn originated on days 12-14 of gestation. The neurons that originated on days 10 and 11 originated and migrated primarily from the basal plate, and they settled in the adjacent regions of the intermediate zone; those neurons formed on days 12-14 originated and migrated primarily from the alar plate, and it was concluded that these neuroblasts similarly settled in the adjacent regions of the intermediate zone. Extraventricular proliferation, which presumably signaled the initial stages of gliogenesis, was first observed on day 12 of gestation. This study supports the classical idea of the mosaic pattern of neurogenesis in the embryonic spinal cord. (Auth.)

  18. Tissue fixation and autoradiographic negative chemography in rat oral epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Prime, S.S.; MacDonald, D.G. (Glasgow Dental Hospital (UK))

    1983-01-01

    The effect of routine methods of tissue fixation on autoradiographic negative chemography was investigated in adult rat palatal and tongue epithelia following the incorporation of /sup 3/H thymidine in vivo. Tissues fixed in formalin or Bouin's without acetic acid demonstrated more negative chemography than those fixed in Bouin's fluid, formol-acetic-methanol or Carnoy's solutions. These findings were associated with the lowest silver grain counts per nucleus in the formalin fixed tissues, low grain counts in tissues fixed in Bouin's without acetic acid, but the addition of acetic acid to make complete Bouin's fluid gave results similar to those following fixation with Carnoy's solution. The highest silver grain counts were obtained with tissues fixed in formol-acetic-methanol. The relationship between negative chemography and the labelling indices of tissues was unclear except where the negative chemographic effects were severe. Formalin fixed tissues showed the maximum negative chemographic effects and the lowest labelling indices. Carnoy's solution appeared to be the fixative of choice for cell kinetic studies of oral epithelium.

  19. In situ autoradiographic detection of folylpolyglutamate synthetase activity

    International Nuclear Information System (INIS)

    Sussman, D.J.; Milman, G.; Osborne, C.; Shane, B.

    1986-01-01

    The enzyme folylpolyglutamate synthetase (FPGS) catalyzes the conversion of folate (pteroylmonoglutamate) to the polyglutamate forms (pteroylpolyglutamates) that are required for folate retention by mammalian cells. A rapid in situ autoradiographic assay for FPGS was developed which is based on the folate cofactor requirement of thymidylate synthase. Chinese hamster AUX B1 mutant cells lack FPGS activity and are unable to accumulate folate. As a result, the conversion of [6- 3 H]deoxyuridine to thymidine via the thymidylate synthase reaction is impaired in AUX B1 cells and no detectable label is incorporated into DNA. In contrast, FPGS in wild-type Chinese hamster CHO cells causes folate retention and enables the incorporation of [6- 3 H]deoxyuridine into DNA. Incorporation may be detected by autoradiography of monolayer cultures or of colonies replica plated onto polyester discs. Introduction of Escherichia coli FPGS into AUX B1 cells restores the activity of the thymidylate synthase pathway and demonstrates that the E. coli FPGS enzyme can provide pteroylpolyglutamates which functions in mammalian cells

  20. Tissue fixation and autoradiographic negative chemography in rat oral epithelium

    International Nuclear Information System (INIS)

    Prime, S.S.; MacDonald, D.G.

    1983-01-01

    The effect of routine methods of tissue fixation on autoradiographic negative chemography was investigated in adult rat palatal and tongue epithelia following the incorporation of 3 H thymidine in vivo. Tissues fixed in formalin or Bouin's without acetic acid demonstrated more negative chemography than those fixed in Bouin's fluid, formol-acetic-methanol or Carnoy's solutions. These findings were associated with the lowest silver grain counts per nucleus in the formalin fixed tissues, low grain counts in tissues fixed in Bouin's without acetic acid, but the addition of acetic acid to make complete Bouin's fluid gave results similar to those following fixation with Carnoy's solution. The highest silver grain counts were obtained with tissues fixed in formol-acetic-methanol. The relationship between negative chemography and the labelling indices of tissues was unclear except where the negative chemographic effects were severe. Formalin fixed tissues showed the maximum negative chemographic effects and the lowest labelling indices. Carnoy's solution appeared to be the fixative of choice for cell kinetic studies of oral epithelium. (author)

  1. Uranium in bone: metabolic and autoradiographic studies in the rat

    International Nuclear Information System (INIS)

    Priest, N.D.; Haines, J.W.; Howells, G.R.; Green, D.

    1982-01-01

    The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1) Uranium is initially deposited on to all types of bone surface, but preferentially on to those that are accreting. 2) Uranium is deposited in the calcifying zones of skeletal cartilage. 3) Bone accretion results in the burial of surface deposits of uranium. 4) Bone resorption causes the removal of uranium from surfaces. 5) Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6) Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7) The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium. (author)

  2. Uranium in bone: metabolic and autoradiographic studies in the rat.

    Science.gov (United States)

    Priest, N D; Howells, G R; Green, D; Haines, J W

    1982-03-01

    The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1 Uranium is initially deposited onto all types of bone surface, but preferentially onto those that are accreting. 2 Uranium is deposited in the calcifying zones of skeletal cartilage. 3 Bone accretion results in the burial of surface deposits of uranium. 4 Bone resorption causes the removal of uranium from surfaces. 5 Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6 Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7 The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium.

  3. A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Zhizhen [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)], E-mail: zhizhen_zeng@merck.com; O' Brien, Julie A. [Sleep and Psychiatric Disorders, Merck Research Laboratories, West Point, PA 19486 (United States); Lemaire, Wei [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); O' Malley, Stacey S.; Miller, Patricia J. [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States); Zhao Zhijian [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); Wallace, Michael A. [Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065 (United States); Raab, Conrad [Drug Metabolism, Merck Research Laboratories, West Point, PA 19486 (United States); Lindsley, Craig W. [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); Departments of Pharmacology and Chemistry, Vanderbilt University, Nashville, TN 37232 (United States); Sur, Cyrille; Williams, David L. [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)

    2008-04-15

    Introduction: In an effort to develop agents to test the NMDA hypofunction hypothesis of schizophrenia, benchmark compounds from a program to discover potent, selective, competitive glycine transporter 1 (GlyT1) inhibitors were radiolabeled in order to further study the detailed pharmacology of these inhibitors and the distribution of GlyT1 in brain. We here report the in vitro characterization of [{sup 35}S](S)-2-amino-4-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl) ethyl)benzamide ([{sup 35}S]ACPPB), a radiotracer developed from a potent and selective non-sarcosine-derived GlyT1 inhibitor, its use in autoradiographic studies to localize (S)-2-amino-6-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl) benzamide (ACPPB) binding sites in rat and rhesus brain and for in vivo occupancy assays of competitive GlyT1 inhibitors. Methods: Functional potencies of unlabeled compounds were characterized by [{sup 14}C]glycine uptake into JAR (human placental choriocarcinoma) cells and synaptosomes. Radioligand binding studies were performed with tissue homogenates. Autoradiographic studies were performed on tissue slices. Results: ACPPB is a potent (K{sub d}=1.9 nM), selective, GlyT1 inhibitor that, when radiolabeled with [{sup 35}S], is a well-behaved radioligand with low nondisplaceable binding. Autoradiographic studies of rat and rhesus brain slices with this ligand showed that specific binding sites were plentiful and nonhomogeneously distributed, with high levels of binding in the brainstem, cerebellar white matter, thalamus, cortical white matter and spinal cord gray matter. In vivo studies demonstrate displaceable binding of [{sup 35}S]ACPPB in rat brain tissues following iv administration of this radioligand. Conclusions: This is the first report of detailed anatomical localization of GlyT1 using direct radioligand binding, and the first demonstration that an in vivo occupancy assay is feasible, suggesting that it may also be feasible to develop

  4. A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies

    International Nuclear Information System (INIS)

    Zeng Zhizhen; O'Brien, Julie A.; Lemaire, Wei; O'Malley, Stacey S.; Miller, Patricia J.; Zhao Zhijian; Wallace, Michael A.; Raab, Conrad; Lindsley, Craig W.; Sur, Cyrille; Williams, David L.

    2008-01-01

    Introduction: In an effort to develop agents to test the NMDA hypofunction hypothesis of schizophrenia, benchmark compounds from a program to discover potent, selective, competitive glycine transporter 1 (GlyT1) inhibitors were radiolabeled in order to further study the detailed pharmacology of these inhibitors and the distribution of GlyT1 in brain. We here report the in vitro characterization of [ 35 S](S)-2-amino-4-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl) ethyl)benzamide ([ 35 S]ACPPB), a radiotracer developed from a potent and selective non-sarcosine-derived GlyT1 inhibitor, its use in autoradiographic studies to localize (S)-2-amino-6-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl) benzamide (ACPPB) binding sites in rat and rhesus brain and for in vivo occupancy assays of competitive GlyT1 inhibitors. Methods: Functional potencies of unlabeled compounds were characterized by [ 14 C]glycine uptake into JAR (human placental choriocarcinoma) cells and synaptosomes. Radioligand binding studies were performed with tissue homogenates. Autoradiographic studies were performed on tissue slices. Results: ACPPB is a potent (K d =1.9 nM), selective, GlyT1 inhibitor that, when radiolabeled with [ 35 S], is a well-behaved radioligand with low nondisplaceable binding. Autoradiographic studies of rat and rhesus brain slices with this ligand showed that specific binding sites were plentiful and nonhomogeneously distributed, with high levels of binding in the brainstem, cerebellar white matter, thalamus, cortical white matter and spinal cord gray matter. In vivo studies demonstrate displaceable binding of [ 35 S]ACPPB in rat brain tissues following iv administration of this radioligand. Conclusions: This is the first report of detailed anatomical localization of GlyT1 using direct radioligand binding, and the first demonstration that an in vivo occupancy assay is feasible, suggesting that it may also be feasible to develop positron emission

  5. C14 Assays and Autoradiographic Studies on the Rooster Comb

    Science.gov (United States)

    Balazs, Endre A.; Szirmai, John A.; Bergendahl, Gudrun

    1959-01-01

    The distribution of C14 was studied in various parts of the rooster comb following treatment with testosterone. The value of gas-phase assay of C14 in tissue has been demonstrated and the results compared with those of autoradiographic studies on the same tissue. The results of these experiments showed that androgen treatment significantly increases the rate of incorporation of C14 in various parts of the comb. The specific activity of carbon in the comb, cornea, and liver differed, depending on which precursor, viz. glucose-6-C14, glucose-1-C14, and glucuronolactone-U-C14, was administered. The highest values were obtained after the administration of glucose-6-C14; glucuronolactone-U-C14 gave the lowest specific activity. The specific activity of carbon in different parts of the comb showed considerable variation. Carbon assay of serial sections of the comb cut at various planes showed that the specific activity of carbon was highest in the mucoid layer. Both C14 assays and autoradiograms indicate that C14 is also present in other parts of the comb. As seen in autoradiography, the concentration of C14 was highest in the epithelium, in the blood vessel walls, and in the avascular collagenous tissue. These results, and indications from previous studies, suggest that the high specific activity of carbon in the mucoid layer is due mainly to the presence of C14-labelled hyaluronic acid. Autoradiograms and PAS staining suggest that a significant amount of C14 is also incorporated into the glycoproteins associated with the collagen fibers. PMID:13654453

  6. Quantitation of DNA repair in brain cell cultures: implications for autoradiographic analysis of mixed cell populations

    International Nuclear Information System (INIS)

    Dambergs, R.; Kidson, C.

    1979-01-01

    Quantitation of DNA repair in the mixed cell population of mouse embryo brain cultures has been assessed by autoradiographic analysis of unscheduled DNA synthesis following UV-irradiation. The proportion of labelled neurons and the grain density over neuronal nuclei were both less than the corresponding values for glial cells. The nuclear geometries of these two classes of cell are very different. Partial correction for the different geometries by relating grain density to nuclear area brought estimates of neuronal and glial DNA repair synthesis more closely in line. These findings have general implications for autoradiographic measurement of DNA repair in mixed cell populations and in differentiated versus dividing cells. (author)

  7. Phaseolus vulgaris leuco-agglutinin immunohistochemistry. A comparison between autoradiographic and lectin tracing of neuronal efferents

    NARCIS (Netherlands)

    Horst, G.J. ter; Karst, H.; Luiten, P.G.M.

    1984-01-01

    The autoradiographic pattern of anterograde labeling as a result from injections with tritiated amino acids is compared to the labeling of efferents with Phaseolus vulgaris leuco-agglutinin after lectin injections in the same nucleus visualized by immunohistochemical methods. This comparison is made

  8. Autoradiographic detection of radionuclides on the epithelial surfaces of pulmonary airways

    International Nuclear Information System (INIS)

    Pappin, J.L.; Filipy, R.E.; Madison, R.M.

    1979-01-01

    We are developing an autoradiographic method for detection of radionuclide deposition sites on the internal surfaces of pulmonary airways. The method is expected to generate information on the distribution as well as on the quantity of radionuclides deposited in pulmonary airways

  9. Computerized pattern recognition used for grain counting in high resolution autoradiographs with low grain densities

    NARCIS (Netherlands)

    Schellart, N. A.; Zweijpfenning, R. C.; van Marle, J.; Huijsmans, D. P.

    1986-01-01

    Using a video-image system coupled to a minicomputer with commercial image handling software, autoradiographic grains displayed in dark-field are counted with a fast (ca. 3.5 min for 120,000 microns 2) and reliable (false scores less than 5%) grain-recognizing FORTRAN program executed in the users

  10. To be, or not to be obese - that's the challenge: a hypothesis on the cortical inhibition of the hypothalamus and its therapeutical consequences.

    Science.gov (United States)

    Kreier, Felix

    2010-08-01

    Today, obesity is the most urgent unsolved medical problem, with the threat of a decreased life expectancy rate for the first time in medical history. Many obese subjects try to lose weight by dieting and exercising, without success on a long term basis. The only therapy with some effect is bariatric surgery with the impact of sustainable adverse effects only suitable in morbid obesity. Why are the therapies to treat obesity not working? Within the last years, we have become more aware of the role of the brain in energy homeostasis. The three main players within the brain controlling our weight are the cortex for cognition, hypothalamus for vital body functions and limbic-reward system for emotions. One hypothesizes that the failure of the cortex to inhibit the hypothalamus is the main cause of obesity. The evolutionary old hypothalamus constantly seeks for a positive energy balance, always in endeavor to avoid any energy shortage in the future. The hypothalamus is executing its tasks in a parallel mode. It can coordinate a set of vital routines independently, yet simultaneously. For e.g., energy balance, salt balance, body temperature and sleep are executed even in a coma. The hypothalamus is primitive but stable. The cortex in humans is, compared to rodents, much bigger and more complex, while the hypothalamus bears more similarities between these two species. The cortex in humans is evolutionary younger and represents higher cognition, an unique human feature. In contrast to the hypothalamus, the cortex focuses on one problem at a time, thus functioning on an attention-based manner. Due to this serial mode, the cortex uses a large part of its capacity for one problem at a time. Therefore, it can solve more complex calculations than the hypothalamus by thinking about one problem after another. It is even strong enough to veto the hypothalamus, if necessary. If the concentration on weight loss is distorted, the hypothalamus is free of inhibition by the cortex, and

  11. Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

    Science.gov (United States)

    Martyniuk, Christopher J.; Feswick, April; Spade, Daniel J.; Kroll, Kevin J.; Barber, David S.; Denslow, Nancy D.

    2010-01-01

    Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female largemouth bass (LMB) to an acute treatment of dieldrin. Male and female LMB were injected with either vehicle or 10 mg dieldrin/kg and sacrificed after seven days. There were no significant changes in dopamine or DOPAC concentrations in the neuroendocrine brain of males and females after treatment but GABA levels in females were moderately increased 20–30% in the hypothalamus and cerebellum. In the female hypothalamus, there were 227 transcripts (p<0.001) identified as being differentially regulated by dieldrin. Functional enrichment analysis revealed transcription, DNA repair, ubiquitin-proteasome pathway, and cell communication, as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimer’s disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are also associated with the etiology of human neurological disorders. PMID:20438755

  12. Activity changes of the cat paraventricular hypothalamus during stressor exposure

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, David M; Poe, Gina R

    2004-01-01

    Dorso-medial paraventricular hypothalamus (PVH) activity was assessed by light scattering procedures in freely behaving cats during auditory stressor exposure. Acoustic noise (> 95dB) raised plasma ACTH concentrations, somatic muscle tonus, respiratory frequency and cardiac rates; PVH activity...

  13. Noradrenergic and GABAergic systems in the medial hypothalamus are activated during hypoglycemia

    NARCIS (Netherlands)

    Beverly, JL; De Vries, MG; Bouman, SD; Arseneau, LM

    Noradrenergic and GABAergic systems in the medial hypothalamus influence plasma glucose and may be activated during glucoprivation. Microdialysis probes were placed into the ventromedial nucleus (VMH), lateral hypothalamus (LHA), and paraventricular nucleus (PVH) of male Sprague-Dawley rats to

  14. Tritiated 2-deoxy-D-glucose: a high-resolution marker for autoradiographic localization of brain metabolism

    International Nuclear Information System (INIS)

    Hammer, R.P. Jr.; Herkenham, M.

    1984-01-01

    The technique for autoradiographic localization of 2-deoxy-D-glucose (2DG) uptake has become a useful method for observing alterations of functional brain activity resulting from experimental manipulation. Autoradiographic resolution is improved using tritiated ([3H]) rather than carbon-14 ([14C)]2DG, due to the lower energy and shorter path of tritium emissions. In addition, lower 2DG uptake by white matter relative to gray matter is exaggerated in the [3H]2DG autoradiographs due to the greater absorption of tritium emissions by lipids. Using [3H]2DG, it is possible to observe differential metabolic labeling in various individual nuclei or portions of nuclei that is unresolvable using [14C]2DG in the awake, normal animal. Heterogeneous patterns of 2DG uptake seen only with [3H]2DG are found in the nucleus accumbens, the anterior portion of the basolateral nucleus of the amygdala, specific nuclei of the inferior olivary complex, various hypothalamic regions, and a region straddling the border of the medial and lateral habenular nuclei. The lamination of differential 2DG uptake in the hippocampus is better localized using [3H]2DG. Autoradiographic resolution of labeled 2DG is further improved when the brain is perfused prior to frozen sectioning, due perhaps to selective fixation and retention of intracellular labeled 2-deoxy-glycogen. A series of [3H]2DG autoradiographs are presented together with views of the Nissl-stained sections that produced the autoradiographs

  15. Structural and functional sex differences in the human hypothalamus

    NARCIS (Netherlands)

    Swaab, D. F.; Chung, W. C.; Kruijver, F. P.; Hofman, M. A.; Ishunina, T. A.

    2001-01-01

    Sex differences in the brain may be the basis not only for sex differences in reproduction, gender identity (the feeling of being male or female), and sexual orientation (heterosexuality vs homosexuality), but also for the sex difference in prevalence of psychiatric and neurological diseases ( Swaab

  16. File list: Unc.Neu.10.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: ALL.Neu.10.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: ALL.Neu.05.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: ALL.Neu.50.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: ALL.Neu.20.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Unc.Neu.20.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.20.AllAg.Hypothalamus mm9 Unclassified Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.20.AllAg.Hypothalamus.bed ...

  2. File list: Unc.Neu.05.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Unc.Neu.50.AllAg.Hypothalamus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Hypothalamus mm9 Unclassified Neural Hypothalamus SRX956253,SRX956...254 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Hypothalamus.bed ...

  4. Electron autoradiographic study of intracellular conversion of fatty acids into glycogen in rats with alloxan diabetes

    International Nuclear Information System (INIS)

    Lebkova, N.P.; Bobkov, Y.I.; Gorbonova, V.D.; Kolesova, O.E.

    1985-01-01

    An electron-autoradiographic study was undertaken of the intracellular distribution of hydrogen of fatty acids in alloxan diabetes. Alloxan diabetes was induced in rats; between 2 weeks and 2 months after development of the disease 0.1 ml of tritium-oleic or tritium-arachidonic acid was injected into the caudel vein of the rats. After decapitation, myocardial tissue from the subendocardial zone of the left ventricle, liver tissue, and glycogen isolated from the liver by a biochemical method, were taken for electron-autoradiographic investigation. Analysis of the data showed that a radioactive isotope, injected into the blood stream of the animals in the form of oleic or arachidonic acids, is incorporated into various structures of hepatocytes and cardiomyocytes. Direct proof is obtained to show that glycogen in hepatocytes and cardiomyoctyes of diabetic rats may be formed from fatty acids

  5. Alkylmercurial encephalopathy in the monkey (Saimiri sciureus and Macaca Arctoides); a histopathologic and autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Garman, R H; Weiss, B; Evans, H L

    1975-01-01

    Histopathologic and autoradiographic studies were performed on monkeys of the genera Saimiri and Macaca after acute and chronic oral exposure to several dosage regimens of methylmercuric chloride (MeHg). Neuropathologic changes were primarily cortical, although subcortical lesions also were observed. Autoradiographic localization of /sup 203/Hg was greatest within glial cells (particularly Nissl-plump astrocytes, subependymal glia and Bergmann's glia) and mast cells. High levels of label within normal appearing large neurons (particularly those within Gasserian and dorsal root ganglia) indicate a lower susceptibility of these neurons to the toxic effects of MeHg. Blood and brain levels of mercury correlated well with the degree of neuropathologic change, but individual variations in susceptibility to intoxication also existed. (auth)

  6. An autoradiographic study on the distribution of 14C-glycine in clonorchis sinensis

    International Nuclear Information System (INIS)

    Lee, S.H.; Song, C.Y.

    1977-01-01

    To study an aspect of protein metabolism in chinese liverfluke, Clonorchis sinensis, an autoradiographic study was performed. A batch of 25 ml erlenmeyer flasks, each flask containing 10 worms of C. sinensis and 10 ml of Tyrode medium with 2.5 μCi/ml of 14 C-glycine, was incubated for 1 hour in Dubnoff metabolic shaking incubator at 37 0 C. Those worms were processed for microautoradiography immediately after the incubation, and following results were obtained from the autoradiographs. The densities of black silver grains derived from 14 C-glycine were the most apparent in the subparenchymal cells, intestinal epithelium, vitelline gland cells, ovary and the wall of the seminal vesicle. Moderate grade of densities were observed in the tegument, oral sucker, pharynx, intestinal content and in the testes. The reticular tissue, ventral sucker, uterus with eggs, seminal receptacle and the content of seminal vesicle showed trace amount of silver grains. (author)

  7. Autoradiographic study of gamma-ray induced unscheduled DNA synthesis in bean root meristem cells

    International Nuclear Information System (INIS)

    Liu Zhenshen; Qiu Quanfa; Chen Dongli

    1989-01-01

    The gamma-ray induced unscheduled DNA synthesis in root meristem cells of Vica faba was studied autoradiographically by calculating the number of cells with different 3H-thymidine labelling degree. It was found that the level of unscheduled synthesis in cells with intermediate dose (500 R) irradiation was higher than that in cells with lower dose (250 R) irradiation; however, higher dose (1000 R) irradiation would inhibit the reparative replication

  8. Autoradiographical Detection of Tritium in Cu-Ni Alloy by Scanning Electron Microscopy

    OpenAIRE

    高安, 紀; 中野, 美樹; 竹内, 豊三郎

    1981-01-01

    The autoradiograph of tritium dispersed in Cu-Ni alloy sheet by 6Li(n,α)3H reaction was obtained by a scanning electron microscope. Prior to the irradiation of neutrons 6Li was deposited on the sheet by evaporation. The liquid emulsion, Fuji-ER, was used in this study. The distribution of tritium was detected by the dispersion of silver grains remaining in the emulsion after the development was carried out.

  9. Development of autoradiographic method for measuring sorption of radionuclides on natural fracture surfaces

    International Nuclear Information System (INIS)

    Muuronen, S.

    1983-11-01

    On the basis of positive results about sorption of radionuclides in rock thin sections an autoradiographic method applicable for measurement sorption of radionuclides on rough rock surfaces was developed. There is no method available because 1) a plane film cannot be used because due to the roughness of rock surfaces 2) rock samples used in this investigation cannot be studied with microscopes and 3) autoradiogram cannot be studied fixed on the surface of a rock sample because the colours of the minerals in the sample will interfere with the interpretation. This report discusses experimental work done to find an useful proedure. In the development of the method main emphasis was put on investigation of the following steps: 1) preparation of the sample for equilibration and spiking; 2) properties of the covering paint for the rock surface and 3) testing of autoradiographic methods using different nuclear emulsions. As the result of these experiments promising autoradiograms with gel emulsion for sawed rock surfaces and with stripping film for rough rock surfaces were obtained. The mineralogic disribution of sorbed activity is easily seen in autoradiograms. Much work must still be done to get reliable quantitative information from autoradiograms. For developing of the autoradiographic method sawed plane rock samples of quartz feldspar intergrowth, pegmatite and limestone were used. In addition core samples of tonalite and mica gneiss from Olkiluoto were utilized. The distribution coefficients (Ksub(a)) obtained for cesium were 560 x 10 -4 and 620 x 10 -4 m 3 /m 2 for tonalite and mica gneiss, respectively. The results are little higher but of the same order of magnitude as obtained by the autoradiographic method using rock thin sections and by the batch method using crused samples. The natural fracture surface sorption study is a logical step in determining the scaling factor from laboratory to field studies. Field data will be needed to determine whether laboratory

  10. Autoradiographic localization of substance P receptors using 125I substance P

    International Nuclear Information System (INIS)

    Shults, C.W.; Quirion, R.; Jensen, R.T.; Moody, T.W.; O'Donohue, T.L.; Chase, T.N.

    1982-01-01

    This paper describes a method for localization of substance P receptors in the rat central nervous system using 125 I labeled substance P in an autoradiographic procedure. Particularly high densities of substance P receptors were observed in the olfactory bulb, dentate gyrus, amygdala, superior colliculus, and locus coeruleus. Surprisingly low densities of substance P receptors were found in the substantia nigra pars reticulata, a region which contains high concentrations of substance P

  11. Detection of antisalivary duct antibody from Sjoegren's syndrome by an autoradiographic method

    International Nuclear Information System (INIS)

    Cummings, N.A.; Tarpley, T.M. Jr.

    1978-01-01

    A new technique to detect anti-salivary duct antibody (ASDA) has been developed by using autoradiographic, rather than immunofluorescent methods. The antibody activity detected by autoradiography is probably classic ASDA. Both techniques may be consecutively performed on the same tissue section without attenuation of either. Some of the potential advantages of the radiolabelling of ASDA are pointed out, and a few preliminary experiments using the labelled antibody as a marker are presented. (Auth.)

  12. Detection of antisalivary duct antibody from Sjögren's syndrome by an autoradiographic method.

    Science.gov (United States)

    Cummings, N A; Tarpley, T M

    1978-01-01

    A new technique to detect anti-salivary duct antibody (ASDA) has been developed by using autoradiographic, rather than immunofluorescent methods. The antibody activity detected by autoradiography is probably classic ASDA. Both techniques may be consecutively performed on the same tissue section without attenuation of either. Some of the potential advantages of the radiolabelling of ASDA are pointed out, and a few preliminary experiments using the labelled antibody as a marker are presented.

  13. Metallographic and autoradiographic investigation of the structure of centrifugally cast steel

    International Nuclear Information System (INIS)

    Singh, K.N.; Krishna Rao, P.

    1981-01-01

    Metallographic and autoradiographic investigations were carried out on the structure of steel tubes cast in a horizontal axis centrifugal casting machine. In chill castings the chill and columnar zones showed significantly lower sulphur contents than the equiaxed zone. Mould rotational speed was found to have an important influence on sulphur segregation. Sulphur-depleted bands, which were often observed in the castings were found to arise due to minor variations in the mould rotational speed. (auth.)

  14. Autoradiographic studies on glucose metabolism in the salivary gland of Lygaeus SP. (Heteroptera, Lygalidae)

    International Nuclear Information System (INIS)

    Kumar, D.

    1985-01-01

    Autoradiographic studies using 3H-glucose in the salivary glands of Lygaeus sp.were carried out. It has been observed that the radioactivity appears in the cell cytoplasm and lumen within a short period of incubation and attains its peak after 30 min of incubation. Afterwards, the radioactivity is exhausted from the cell and lumen suggesting a very high rate of glucose metabolism in this species. (author) [pt

  15. NPY intraperitoneal injections produce antidepressant-like effects and downregulate BDNF in the rat hypothalamus.

    Science.gov (United States)

    Gelfo, Francesca; Tirassa, Paola; De Bartolo, Paola; Croce, Nicoletta; Bernardini, Sergio; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

    2012-06-01

    Several studies have documented an involvement of Neuropeptide Y (NPY) in stress-related disorders. Stress-related disorders are also characterized by changes in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), neurotrophins implicated in the survival and function of neurons. Thus the aim of this study was to investigate whether an NPY intraperitoneal treatment has antidepressant-like effects in rats subjected to a classical stress paradigm, the Forced Swim Test (FST), in association with changes in local brain neurotrophin production. Rats were intraperitoneally injected with either NPY (60 μg/kg) or a vehicle for three consecutive days between two FST sessions and then tested for time spent (or delay onset) in immobile posture. Moreover, we measured by enzyme-linked immunosorbent assay (ELISA) neurotrophin levels in the hypothalamus and corticosterone levels in plasma. The data showed that NPY induced a significant delay in the onset and a significant reduction in the duration of the immobility posture in FST. We also found that NPY decreased BDNF levels in the hypothalamus and corticosterone levels in plasma. Immobility posture in FST can be reduced by antidepressant drugs. Thus, our data show an antidepressant-like effect of NPY associated with changes in BDNF levels in the hypothalamus and reduced activity of hypothalamic-pituitary-adrenal (HPA) axis. These findings, while confirming the involvement of the NPY system in stress-related disorders, suggest that a less invasive route of administration, such as an intraperitoneal injection, may be instrumental in coping with stressful events in animal models and perhaps in humans. © 2012 Blackwell Publishing Ltd.

  16. Ultra-high performance, solid-state, autoradiographic image digitization and analysis system

    International Nuclear Information System (INIS)

    Lear, J.L.; Pratt, J.P.; Ackermann, R.F.; Plotnick, J.; Rumley, S.

    1990-01-01

    We developed a Macintosh II-based, charge-coupled device (CCD), image digitization and analysis system for high-speed, high-resolution quantification of autoradiographic image data. A linear CCD array with 3,500 elements was attached to a precision drive assembly and mounted behind a high-uniformity lens. The drive assembly was used to sweep the array perpendicularly to its axis so that an entire 20 x 25-cm autoradiographic image-containing film could be digitized into 256 gray levels at 50-microns resolution in less than 30 sec. The scanner was interfaced to a Macintosh II computer through a specially constructed NuBus circuit board and software was developed for autoradiographic data analysis. The system was evaluated by scanning individual films multiple times, then measuring the variability of the digital data between the different scans. Image data were found to be virtually noise free. The coefficient of variation averaged less than 1%, a value significantly exceeding the accuracy of both high-speed, low-resolution, video camera (VC) systems and low-speed, high-resolution, rotating drum densitometers (RDD). Thus, the CCD scanner-Macintosh computer analysis system offers the advantage over VC systems of the ability to digitize entire films containing many autoradiograms, but with much greater speed and accuracy than achievable with RDD scanners

  17. Detection of antibodies to transmissible gastroenteritis virus of swine by modified autoradiographic test

    Energy Technology Data Exchange (ETDEWEB)

    Stepanek, J; Hampl, J; Franz, J; Mensik, P; Skrobak, F [Vyzkumny Ustav Veterinarniho Lekarstvi, Brno-Medlanky (Czechoslovakia)

    1982-08-01

    A modified method of autoradiographic determination of virus antibodies of gastroenteritis of swine was developed. It is based on the actual reaction between antigen bound in cells of the infected cell cultures and antibodies in tested sera, which is visualized by rabbit antibodies labelled with /sup 125/I (/sup 125/I RaSw IgG antibody) to porcine IgG, on a sensitive radiograph and evaluated by darkening at the point of positive immunological reaction. Specificity of the test and mutual comparability and reproducibility of the results were confirmed by examining the known positive and negative sera and by a comparison with the results of the virus-neutralization test. Of the 36 examined porcine blood sera, antibodies were only proved autoradiographically in the samples positive also by virus-neutralization. In experimentally infected pigs, the same dynamics of antibody production was recorded by the two tests. They were, however, demonstrated autoradiographically the eighth day after infection, while by virus neutralization test as late as 14th day. Their level increased gradually till 35th day after infection.

  18. Comparative autoradiographic investigations on the tissue distribution of benfotiamine versus thiamine in mice.

    Science.gov (United States)

    Hilbig, R; Rahmann, H

    1998-05-01

    The tissue distribution of two therapeutically applied preparations of B-vitamins were investigated in blood and selected organs (liver, brain, muscle, kidney) of laboratory mice using autoradiographic techniques. Incorporation of lipid-soluble 3H-benfotiamine (CAS 22457-89-2) and water-soluble 3H-thiaminehydrochloride (CAS 67-03-8) (200 microCi, equivalent to 105 mg vitamin/kg body weight) was monitored between 0.75 and 168 h after an oral or subcutaneous administration. The labelled tissue slices were autoradiographically analysed after a differential histochemical extraction procedure to evaluate the respective total radioactivity, the uptake into lipid-soluble, water-soluble and residual macromolecular compounds. Evaluation of these autoradiographic data (given as mumol vitamin preparation/mg tissue equivalent) proved that benfotiamine is incorporated much better than thiaminehydrochloride independent of the administration mode. In muscle and brain tissue a 5 to 25 fold higher amount of tracer incorporation was registered following benfotiamine as compared with the thiamine application, whereas in all other organs the difference in the label was mostly between 10 and 40%. Concerning the organ specific distribution, liver and kidney were the structures labelled highest by both substances and administration procedures. In the liver, concerning all incorporation times, a higher proportion of residual macromolecular compounds was found, whereas in the kidney the proportions of lipid- as well as of water-soluble materials prevailed. These data should be clinically relevant.

  19. Social Control of Hypothalamus-Mediated Male Aggression.

    Science.gov (United States)

    Yang, Taehong; Yang, Cindy F; Chizari, M Delara; Maheswaranathan, Niru; Burke, Kenneth J; Borius, Maxim; Inoue, Sayaka; Chiang, Michael C; Bender, Kevin J; Ganguli, Surya; Shah, Nirao M

    2017-08-16

    How environmental and physiological signals interact to influence neural circuits underlying developmentally programmed social interactions such as male territorial aggression is poorly understood. We have tested the influence of sensory cues, social context, and sex hormones on progesterone receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) that are critical for male territorial aggression. We find that these neurons can drive aggressive displays in solitary males independent of pheromonal input, gonadal hormones, opponents, or social context. By contrast, these neurons cannot elicit aggression in socially housed males that intrude in another male's territory unless their pheromone-sensing is disabled. This modulation of aggression cannot be accounted for by linear integration of environmental and physiological signals. Together, our studies suggest that fundamentally non-linear computations enable social context to exert a dominant influence on developmentally hard-wired hypothalamus-mediated male territorial aggression. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Metabolic mystery: Aging, obesity, diabetes and ventromedial hypothalamus

    OpenAIRE

    Mobbs, Charles V.; Moreno, Cesar L.; Poplawski, Michael

    2013-01-01

    We propose that energy balance, glucose homeostasis, and aging are all regulated largely by the same nutrient-sensing neurons in the ventromedial hypothalamus (VMH)., Although the central role of these neurons in regulating energy balance is clear, their role in regulating glucose homeostasis has only become more clear recently. It is the latter function that may be most relevant to aging and lifespan, by controlling the rate of glucose metabolism. Specifically, glucose-sensing neurons in VMH...

  1. Short-term fasting promotes insulin expression in rat hypothalamus.

    Science.gov (United States)

    Dakic, Tamara B; Jevdjovic, Tanja V; Peric, Mina I; Bjelobaba, Ivana M; Markelic, Milica B; Milutinovic, Bojana S; Lakic, Iva V; Jasnic, Nebojsa I; Djordjevic, Jelena D; Vujovic, Predrag Z

    2017-07-01

    In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6-h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Sonic hedgehog signaling in the development of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Sandra eBlaess

    2015-01-01

    Full Text Available The expression pattern of Sonic Hedgehog (Shh in the developing hypothalamus changes over time. Shh is initially expressed in the prechordal mesoderm and later in the hypothalamic neuroepithelium-- first medially, and then in two off-medial domains. This dynamic expression suggests that Shh might regulate several aspects of hypothalamic development. To gain insight into them, lineage tracing, (conditional gene inactivation in mouse, in ovo loss- and gain-of-function approaches in chick and analysis of Shh expression regulation have been employed. We will focus on mouse studies and refer to chick and fish when appropriate to clarify. These studies show that Shh-expressing neuroepithelial cells serve as a signaling center for neighboring precursors, and give rise to most of the basal hypothalamus (tuberal and mammillary regions. Shh signaling is initially essential for hypothalamic induction. Later, Shh signaling from the neuroepithelium controls specification of the lateral hypothalamic area and growth-patterning coordination in the basal hypothalamus. To further elucidate the role of Shh in hypothalamic development, it will be essential to understand how Shh regulates the downstream Gli transcription factors.

  3. Neuromyelitis optica spectrum disorder presenting with repeated hypersomnia due to involvement of the hypothalamus and hypothalamus-amygdala linkage.

    Science.gov (United States)

    Kume, Kodai; Deguchi, Kazushi; Ikeda, Kazuyo; Takata, Tadayuki; Kokudo, Yohei; Kamada, Masaki; Touge, Tetsuo; Takahashi, Toshiyuki; Kanbayashi, Takashi; Masaki, Tsutomu

    2015-06-01

    We report the case of a 46-year-old Japanese woman with neuromyelitis optica spectrum disorder presenting with repeated hypersomnia accompanied by decreased CSF orexin level. First episode associated with hypothalamic-pituitary dysfunction showed bilateral hypothalamic lesions that can cause secondary damage to the orexin neurons. The second episode associated with impaired memory showed a left temporal lesion involving the amygdala. The mechanism remains unknown, but the reduced blood flow in the hypothalamus ipsilateral to the amygdala lesion suggested trans-synaptic hypothalamic dysfunction secondary to the impaired amygdala. A temporal lesion involving the amygdala and hypothalamus could be responsible for hypersomnia due to neuromyelitis optica spectrum disorder. © The Author(s), 2015.

  4. Transcriptome analyses identify five transcription factors differentially expressed in the hypothalamus of post- versus prepubertal Brahman heifers.

    Science.gov (United States)

    Fortes, M R S; Nguyen, L T; Weller, M M D C A; Cánovas, A; Islas-Trejo, A; Porto-Neto, L R; Reverter, A; Lehnert, S A; Boe-Hansen, G B; Thomas, M G; Medrano, J F; Moore, S S

    2016-09-01

    Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: , , , , and . These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric ( cancer and developmental processes. Mutations in were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy.

  5. Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus.

    Directory of Open Access Journals (Sweden)

    Cecilia Berg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI fluoxetine (FLU, Prozac® is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

  6. Calcium antagonist binding sites in the rat brain: Quantitative autoradiographic mapping using the 1, 4-Dihydropyridines [3H]PN 200-110 and [3H]PY 108-068

    International Nuclear Information System (INIS)

    Cortes, R.; Supavilai, P.; Karobath, M.; Palacios, J.M.

    1984-01-01

    An in vitro autoradiographic technique has been used for the quantitative mapping of calcium antagonist binding sites (CABS) in the rat brain, using the 1, 4-dihydropyridines [ 3 H]PN 200-110 and [ 3 H]PY 108-068 as ligands. CABS were distributed throughout the brain in a highly heterogeneous fashion. The highest densities of CABS were observed in the olfactory bulb, hippocampus and parts of the amygdala. The neocortex was also rich in CABS. The basal ganglia, thalamus and hypothalamus presented intermediate levels of CABS while low densities of sites were seen in areas such as the cerebellum, pons and white matter tracts. The distributions of CABS in brain does not correlate with indexes of brain blood flow, regional glucose utilization or the distributions of receptor binding sites for drugs and neurotransmitters analyzed until now. No correlation exists between CABS distribution and that of any neurotransmitter or brain enzyme described so far. The heterogeneous distributions of CABS is suggestive of a neuronal localization, an idea supported by lesion experiments. (Author)

  7. Calcium antagonist binding sites in the rat brain: Quantitative autoradiographic mapping using the 1, 4-dihydropyridines (TH)PN 200-110 and (TH)PY 108-068

    Energy Technology Data Exchange (ETDEWEB)

    Cortes, R.; Supavilai, P.; Karobath, M.; Palacios, J.M.

    1984-01-01

    An in vitro autoradiographic technique has been used for the quantitative mapping of calcium antagonist binding sites (CABS) in the rat brain, using the 1, 4-dihydropyridines (TH)PN 200-110 and (TH)PY 108-068 as ligands. CABS were distributed throughout the brain in a highly heterogeneous fashion. The highest densities of CABS were observed in the olfactory bulb, hippocampus and parts of the amygdala. The neocortex was also rich in CABS. The basal ganglia, thalamus and hypothalamus presented intermediate levels of CABS while low densities of sites were seen in areas such as the cerebellum, pons and white matter tracts. The distributions of CABS in brain does not correlate with indexes of brain blood flow, regional glucose utilization or the distributions of receptor binding sites for drugs and neurotransmitters analyzed until now. No correlation exists between CABS distribution and that of any neurotransmitter or brain enzyme described so far. The heterogeneous distributions of CABS is suggestive of a neuronal localization, an idea supported by lesion experiments. (Author).

  8. Substance P release from rat hypothalamus and spinal cord

    International Nuclear Information System (INIS)

    Kronheim, S.; Sheppard, M.C.; Pimstone, B.L.

    1980-01-01

    A specific and sensitive radioimmunoassay for substance P has been developed to study the release of immunoreactive substance P from incubated rat hypothalamus and rat spinal cord in vitro. Release was significantly increased in the presence of two depolarizing stimuli (56 mM KCl and 75 μM veratrine) and was calcium-dependent. The released immunoreactive material diluted in parallel with synthetic substance P and showed close identity on Sephadex chromatography. A neuromodulator role for the peptide in the central nervous system is suggested

  9. Development of the indusium griseum. 3. An autoradiographic study of cell production

    Energy Technology Data Exchange (ETDEWEB)

    Sturrock, R R [Dundee Univ. (UK)

    1978-05-01

    An autoradiographic study of neuronal and glial production was carried out in the indusium griseum of mice whose mothers had received an intraperitoneal injection of (/sup 3/H)thymidine during gestation. Most neurons were produced between 13 and 15 days post-conception. One part of the glial population underwent its last or second-last divisions between 14 and 16 days post-conception, while the other continued to undergo a number of divisions into postnatal life. It is suggested that the former were astrocytes and the latter oligodendrocytes.

  10. JULIDE: a software tool for 3D reconstruction and statistical analysis of autoradiographic mouse brain sections.

    Directory of Open Access Journals (Sweden)

    Delphine Ribes

    Full Text Available In this article we introduce JULIDE, a software toolkit developed to perform the 3D reconstruction, intensity normalization, volume standardization by 3D image registration and voxel-wise statistical analysis of autoradiographs of mouse brain sections. This software tool has been developed in the open-source ITK software framework and is freely available under a GPL license. The article presents the complete image processing chain from raw data acquisition to 3D statistical group analysis. Results of the group comparison in the context of a study on spatial learning are shown as an illustration of the data that can be obtained with this tool.

  11. Autoradiographic technique for rapid inventory of plutonium-containing fast critical assembly fuel

    International Nuclear Information System (INIS)

    Brumbach, S.B.; Perry, R.B.

    1977-10-01

    A nondestructive autoradiographic technique is described which can provide a verification of the piece count and the plutonium content of plutonium-containing fuel elements. This technique uses the spontaneously emitted gamma rays from plutonium to form images of fuel elements on photographic film. Autoradiography has the advantage of providing an inventory verification without the opening of containers or the handling of fuel elements. Missing fuel elements, substitution of nonradioactive material, and substitution of elements of different size are detectable. Results are presented for fuel elements in various storage configurations and for fuel elements contained in a fast critical assembly

  12. Study on the metabolism of contamination of radioactive materials in organism by autoradiographic techniques

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Zhang Lansheng; Kang Baoan

    1988-08-01

    The metabolism of contamination of radioactive materials in organism was studied by diferent types of autoradiographic techniques, such as: (1) in body level by whole-body autoradiography; (2) in organ level by whole-organ autoradiography; (3) in cellular level by microautoradiography; (4) in subcellular level by electron microscopic autoradiography; (5) in combinative form by tissue fixative autoradiography; (6) in ionizing form by freezing autoradiography; (7) for radioactive mateials with two radionuclides by double radionuclide autoradiography; (8) for radioactive materials with low level of radionuclides by fluorescence sensitization autoradiography; (9) in dissociative products by chromatographic autoradiography

  13. Autoradiographic localization of Na+-K+-ATPase with 3H-ouabain

    International Nuclear Information System (INIS)

    Dormans, J.A.M.A.

    1976-01-01

    Using 3 H-ouabain as an inhibitor, the site of the Na + -K + -ATPase system in cells was determined autoradiographically. Experiments were performed woth guinea pig's kidney tissue. The application of light microscopical autoradiography to freeze-dried tissue showed that especially the distal tubule, and to a smaller extent the proximal tubule and the collecting tubule have Na + -K + -ATPase. Electron microscopical autoradiography showed that this activity is restricted to the baso-lateral plasmamembranes. The quantity of specific bound ouabain turns out to be correlated to the quantity of baso-lateral plasmamembrane's surface

  14. An autoradiographic map of (3H)diprenorphine binding in rat brain: effects of social interaction

    International Nuclear Information System (INIS)

    Panksepp, J.; Bishop, P.

    1981-01-01

    (3H)Diprenorphine binding was analyzed autoradiographically in the brains of 33 day old rat pups. A photographic atlas of diprenorphine binding in the coronal plane is provided to highlight the dispersion of opioid receptor systems through the brain. To determine whether brain opioid release may be induced by social interactions, half the animals were sacrificed following a 30 min period of social interaction while the other half were sacrificed following 30 min of social isolation. Opioid binding was higher in isolate-tested animals than socially-tested ones, suggesting that social interaction may promote endogenous brain opioid release

  15. An improved autoradiographic technique for the detection of antibody-forming cells

    International Nuclear Information System (INIS)

    Mason, D.W.

    1976-01-01

    An autoradiographic technique for the detection of antibody-forming cells has been developed for the assay of anti-DNP responses. The lymphoid cell suspension to be assayed was allowed to sediment on to a glass slide coated with DNP-conjugated gelatin to which the secreted antibody bound during subsequent incubation. The bound antibody and its Ig class was revealed by a second incubation using 125 I-anti-immunoglobulin reagents followed by autoradiography. Studies on the sensitivity and specificity of the method are presented and its advantages over other techniques described. The technique should be readily applicable to other haptens

  16. Double tracer autoradiographic method for sequential evaluation of regional cerebral perfusion

    International Nuclear Information System (INIS)

    Matsuda, H.; Tsuji, S.; Oba, H.; Kinuya, K.; Terada, H.; Sumiya, H.; Shiba, K.; Mori, H.; Hisada, K.; Maeda, T.

    1989-01-01

    A new double tracer autoradiographic method for the sequential evaluation of altered regional cerebral perfusion in the same animal is presented. This method is based on the sequential injection of two tracers, 99m Tc-hexamethylpropyleneamine oxime and N-isopropyl-( 125 I)p-iodoamphetamine. This method is validated in the assessment of brovincamine effects on regional cerebral perfusion in an experimental model of chronic brain ischemia in the rat. The drug enhanced perfusion recovery in low-flow areas, selectively in surrounding areas of infarction. The results suggest that this technique is of potential use in the study of neuropharmacological effects applied during the experiment

  17. Autoradiographic measurement of low concentrations of alpha-active nuclides using CR-39 track detectors

    International Nuclear Information System (INIS)

    Freyer, K.; Dietze, K.; Weisse, S.; Kummer, G.

    1991-01-01

    An autoradiographic method for the determination of alpha emission rates from plastic packaging materials for VLSI silicon memory devices based on long-time exposure of the samples on CR-39 detectors has been tested. The lower limit of detection will be strongly influenced by the background of the detector material and amounts at times to 0.002 alpha particles cm -2 h -1 after 200 days exposure. A mathematical method for the interpretation of very low track densities is discussed. The first results of its application are presented. (author)

  18. Diffusion and autoradiographic investigations of the tritium--304 stainless steel system

    International Nuclear Information System (INIS)

    Downs, G.L.; Braun, J.D.; Chaney, K.F.; Powell, G.W.

    1975-01-01

    The diffusion coefficient of tritium in 304-stainless steel at low temperatures (100 to 300 0 C) was determined. Autoradiography was used to establish the concentration as well as the distribution of tritium in the alloy. The autoradiographic study shows that tritium is distributed heterogeneously at room temperature in the cold-worked alloy and also in the fusion zone of weldments. Tritium partitions preferentially to the delta ferrite in weldments and to martensite produced by the cold working of 304-stainless steel. (auth)

  19. Sensitivity of an autoradiographic film to ionizing radiation of different types and energies

    International Nuclear Information System (INIS)

    Kras, A.B.; Lutzke-Birk, A.; Kalicki, A.

    1984-01-01

    The ORWO-AF3 autoradiographic film has been studied with regard to its sensitivity to beta radiation (E/sub max/ = 0.155 and 0.306 MeV, resp.), gamma radiation of more than 1 MeV and K/sub α/ and K/sub β/ radiation of about 5.9 KeV. The obtained data can be used for the correction of depth distribution profiles if elements are labelled with radioisotopes emitting mixed radiation, e.g., beta and gamma radiation

  20. Autoradiographic and cytochemical studies on the intracellular transport of secreted proteins in the lacrimal ducts (glandula extraorbitalis) of the rat

    International Nuclear Information System (INIS)

    Vogel, H.

    1982-01-01

    Azini was isolated from the glandula lacrimalis of the rat. Its vitality was proven by oxygen use measurements. In autoradiographic studies isolated Azini was marked with L-(4,5- 3 H)-leucine and fixed at various times thereafter. The light microscopic autoradiography showed a time dependent distribution of the silver grains whose association with membrane-enclosed compartments made the electron microscopic autoradiography possible. This distribution allows an analysis of the kinetics of the intracellular transport of secreted proteins. Because of its limited spatial resolution the autoradiographic research methods were combined with the cytochemical presentation of the peroxidase, a secreted protein, of the lacrimal duct. (orig./MG) [de

  1. Distinct types of feeding related neurons in mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Yan eTang

    2016-05-01

    Full Text Available The last two decades of research provided evidence for a substantial heterogeneity among feeding-related neurons (FRNs in the hypothalamus. However, it remains unclear how FRNs differ in their firing patterns during food intake. Here, we investigated the relationship between the activity of neurons in mouse hypothalamus and their feeding behavior. Using tetrode-based in vivo recording technique, we identified various firing patterns of hypothalamic FRNs, which, after the initiation of food intake, can be sorted into four types: sharp increase (type I, slow increase (type II, sharp decrease (type III and sustained decrease (type IV of firing rates. The feeding-related firing response of FRNs was rigidly related to the duration of food intake and, to a less extent, associated with the type of food. The majority of these FRNs responded to glucose and leptin and exhibited electrophysiological characteristics of putative GABAergic neurons. In conclusion, our study demonstrated the diversity of neurons in the complex hypothalamic network coordinating food intake.

  2. Pharmacological characterization and autoradiographic localization of substance P receptors in guinea pig brain

    International Nuclear Information System (INIS)

    Dam, T.V.; Quirion, R.

    1986-01-01

    [ 3 H]Substance P ([ 3 H]SP) was used to characterize substance P (SP) receptor binding sites in guinea pig brain using membrane preparations and in vitro receptor autoradiography. Curvilinear Scatchard analysis shows that [ 3 H]SP binds to a high affinity site (Kd = 0.5 nM) with a Bmax of 16.4 fmol/mg protein and a low affinity site (Kd = 29.6 nM) with a Bmax of 189.1 fmol/mg protein. Monovalent cations generally inhibit [ 3 H]SP binding while divalent cations substantially increased it. The ligand selectivity pattern is generally similar to the one observed in rat brain membrane preparation with SP being more potent than SP fragments and other tachykinins. However, the potency of various nucleotides is different with GMP-PNP greater than GDP greater than GTP. The autoradiographic distribution of [ 3 H]SP binding sites shows that high amounts of sites are present in the hippocampus, striatum, olfactory bulb, central nucleus of the amygdala, certain thalamic nuclei and superior colliculus. The cortex is moderately enriched in [ 3 H]SP binding sites while the substantia nigra contains only very low amounts of sites. Thus, the autoradiographic distribution of SP binding sites is fairly similar in both rat and guinea pig brain

  3. Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

    International Nuclear Information System (INIS)

    Worley, P.F.; Baraban, J.M.

    1987-01-01

    The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using [ 3 H]batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of [ 3 H]BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of [ 3 H]BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizations indicate that [ 3 H]BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations

  4. An autoradiographic study on the distribution of 14C-lactate in clonorchis sinensis

    International Nuclear Information System (INIS)

    Lee, C.S.; Lee, S.H.

    1977-01-01

    The distribution of the exogeneous 14 C-lactate by chines liverfluke Clonorchis sinensis was investigated by autoradiography. The radioactive substance, sodium-DL-lactate-1- 14 C (specific activity; 20-40 mCi/mM) dissolved in Tyrode solution at the concentration of 2.5 μCi/ml was designated as incubation medium. Twenth worms of healthy fluke with 10 ml incubation medium were incubated for 1 hour in Dubnoff shaking incubator at 37 0 C. After incubation, the flukes were rapidly removed from the flask and freed of external radioactivity by a series of washing in cold Tyrode solution. The flukes were fixed in 10% formalin, dehydrated and embeded in paraffin, and were sectioned at the thickness of 5 microns. Then the specimen mounted slides were covered with Kodak AR-10 stripping film and were exposed for 30 days in cold dark room. After the exposure, the film was developed and fixed. Autoradiographs were then stained with hematoxylin and brought to microscopy. The autoradiographs of C. sinensis showed apparent densities of black silver grains derived from the 14 C-lactate in regard to various anatomical structure of the worm. The possible reasons for the appearance radioactive substance in respective organs and tissues of the fluke were discussed. (author)

  5. Autoradiographic demonstration of oxytocin-binding sites in the macula densa

    International Nuclear Information System (INIS)

    Stoeckel, M.E.; Freund-Mercier, M.J.

    1989-01-01

    Specific oxytocin (OT)-binding sites were localized in the rat kidney with use of a selective 125 I-labeled OT antagonist ( 125 I-OTA). High concentrations of OT binding sites were detected on the juxtaglomerular apparatus with use of the conventional film autoradiographic technique. No labeling occurred on other renal structures. The cellular localization of the OT binding sites within the juxtaglomerular apparatus was studied in light microscope autoradiography, on semithin sections from paraformaldehyde-fixed kidney slices incubated in the presence of 125 I-OTA. These preparations revealed selective labeling of the macula densa, mainly concentrated at the basal pole of the cells. Control experiments showed first that 125 I-OTA binding characteristics were not noticeably altered by prior paraformaldehyde fixation of the kidneys and second that autoradiographic detection of the binding sites was not impaired by histological treatments following binding procedures. In view of the role of the macula densa in the tubuloglomerular feedback, the putative OT receptors of this structure might mediate the stimulatory effect of OT on glomerular filtration

  6. Autoradiographic demonstration of oxytocin-binding sites in the macula densa

    Energy Technology Data Exchange (ETDEWEB)

    Stoeckel, M.E.; Freund-Mercier, M.J. (Centre National de la Recherche Scientifique, Strasbourg (France))

    1989-08-01

    Specific oxytocin (OT)-binding sites were localized in the rat kidney with use of a selective {sup 125}I-labeled OT antagonist ({sup 125}I-OTA). High concentrations of OT binding sites were detected on the juxtaglomerular apparatus with use of the conventional film autoradiographic technique. No labeling occurred on other renal structures. The cellular localization of the OT binding sites within the juxtaglomerular apparatus was studied in light microscope autoradiography, on semithin sections from paraformaldehyde-fixed kidney slices incubated in the presence of {sup 125}I-OTA. These preparations revealed selective labeling of the macula densa, mainly concentrated at the basal pole of the cells. Control experiments showed first that {sup 125}I-OTA binding characteristics were not noticeably altered by prior paraformaldehyde fixation of the kidneys and second that autoradiographic detection of the binding sites was not impaired by histological treatments following binding procedures. In view of the role of the macula densa in the tubuloglomerular feedback, the putative OT receptors of this structure might mediate the stimulatory effect of OT on glomerular filtration.

  7. Androstenol--a steroid derived odor activates the hypothalamus in women.

    Directory of Open Access Journals (Sweden)

    Ivanka Savic

    Full Text Available BACKGROUND: Whether pheromone signaling exists in humans is still a matter of intense discussion. In the present study we tested if smelling of Androstenol, a steroid produced by the human body and reported to affect human behavior, may elicit cerebral activation. A further issue was to evaluate whether the pattern of activation resembles the pattern of common odors. METHODOLOGY: PET measurements of regional cerebral blood flow (rCBF were conducted in 16 healthy heterosexual women during passive smelling of Androstenol, four ordinary odors (OO, and odorless air (the base line condition. PRINCIPAL FINDINGS: Smelling Androstenol caused activation of a portion of the hypothalamus, which according to animal data mediates the pheromone triggered mating behavior. Smelling of OO, on the other hand, engaged only the classical olfactory regions (the piriform cortex, lateral amygdala, anterior insular and anterior cingulate cortex. CONCLUSIONS: The observed pattern of activation is very similar to the pattern previously detected with 4,16-androstadien-3-one in heterosexual females. It suggests that several compounds released by human body may activate cerebral networks involved in human reproduction.

  8. Autoradiographic study on the distribution of mercury and its transfer to the egg in the laying quail

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, M; Urakawa, N; Ikeda, M

    1971-01-01

    Autoradiographic and tracer techniques were employed to investigate the distribution and movement of radiomercury in the form of /sup 203/Hg-nitrate, and its transfer to eggs in laying quails. After injection, the radiomercury tended to concentrate in the kidneys and ova, plateauing about 12 hours after injection. Within the egg, the mercury concentrated in the yolk.

  9. Polysaccharides on microsporocytes and tapetum in Rhoeo discolor. Cytochemical and autoradiographic study (/sup 3/H-glucose)

    Energy Technology Data Exchange (ETDEWEB)

    Albertini, L; Souvre, A [Ecole Nationale Superieure Agronomique, 31 - Toulouse (France); Toulouse-3 Univ., 31 (France))

    1978-01-01

    In Rhoeo discolor, we have been studying the evolution of cytoplasmic and wall polysaccharides on microsporocytes and tapetum by cytochemical and autoradiographic (6-/sup 3/H glucose) methods with particular attention to the meiocyte special wall, microspore intine, pollen generative cell wall, microsporocyte plastids and tapetum cytoplasm.

  10. Autoradiographic evidence of sup 125 I-. beta. -endorphin binding sites in the articular cartilage of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Castano, M.T.; Freire-Garabal, M.; Giraldez, M.; Nunez, M.J.; Belmonte, A.; Couceiro, J.; Jorge, J. (Univ. of Santiago (Spain))

    1991-01-01

    After {sup 125}I-{beta}-endorphin was intravenously injected to rats, an autoradiographic study of distal femur articular cartilage was performed. Results show a specific binding of {sup 125}I-{beta}-endorphin to chondrocytes, suggesting the possible existence of an opiate modulation of articular cartilage.

  11. The lateral hypothalamus : A site for integration of nutrient and fluid balance

    NARCIS (Netherlands)

    van Dijk, Gertjan; Evers, Simon S.; Guidotti, Stefano; Thornton, Simon N.; Scheurink, Anton J. W.; Nyakas, Csaba

    2011-01-01

    This paper reviews seemingly obligatory relations between nutrient and fluid balance. A relatively novel neuronal pathway involving interplay between acetylcholine and the melanocortins, alpha MSH and AGRP in the arcuate nucleus (Arc) of the hypothalamus projecting to the lateral hypothalamus (LH)

  12. The neuroanatomical function of leptin in the hypothalamus.

    Science.gov (United States)

    van Swieten, M M H; Pandit, R; Adan, R A H; van der Plasse, G

    2014-11-01

    The anorexigenic hormone leptin plays an important role in the control of food intake and feeding-related behavior, for an important part through its action in the hypothalamus. The adipose-derived hormone modulates a complex network of several intercommunicating orexigenic and anorexigenic neuropeptides in the hypothalamus to reduce food intake and increase energy expenditure. In this review we present an updated overview of the functional role of leptin in respect to feeding and feeding-related behavior per distinct hypothalamic nuclei. In addition to the arcuate nucleus, which is a major leptin sensitive hub, leptin-responsive neurons in other hypothalamic nuclei, including the, dorsomedial-, ventromedial- and paraventricular nucleus and the lateral hypothalamic area, are direct targets of leptin. However, leptin also modulates hypothalamic neurons in an indirect manner, such as via the melanocortin system. The dissection of the complexity of leptin's action on the networks involved in energy balance is subject of recent and future studies. A full understanding of the role of hypothalamic leptin in the regulation of energy balance requires cell-specific manipulation using of conditional deletion and expression of leptin receptors. In addition, optogenetic and pharmacogenetic tools in combination with other pharmacological (such as the recent discovery of a leptin receptor antagonist) and neuronal tracing techniques to map the circuit, will be helpful to understand the role of leptin receptor expressing neurons. Better understanding of these circuits and the involvement of leptin could provide potential sites for therapeutic interventions in obesity and metabolic diseases characterized by dysregulation of energy balance. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. M(o)TOR of aging: MTOR as a universal molecular hypothalamus.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2013-07-01

    A recent ground-breaking publication described hypothalamus-driven programmatic aging. As a Russian proverb goes "everything new is well-forgotten old". In 1958, Dilman proposed that aging and its related diseases are programmed by the hypothalamus. This theory, supported by beautiful experiments, remained unnoticed just to be re-discovered recently. Yet, it does not explain all manifestations of aging. And would organism age without hypothalamus? Do sensing pathways such as MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a "molecular hypothalamus" in every cell? Are hypothalamus-driven alterations simply a part of quasi-programmed aging manifested by hyperfunction and secondary signal-resistance? Here are some answers.

  14. A study of water in glass by an autoradiographic method that utilizes tritiated water

    International Nuclear Information System (INIS)

    Knickerbocker, S.H.; Brown, S.D.; Joshi, S.B.

    1983-01-01

    This chapter determines water concentration and spatial distribution in glass by an autoradiographic method that makes use of tritiated water as the tagged species. Describes the method and presents some typical results. Lists advantages and disadvantages associated with the method and examines other methods that might be used for the study of water in glass. Discusses dry glass preparation, the addition of tritiated water to glass, glass preparation, film selection, and film analysis. Shows tritium autoradiography to be a valuable technique for measuring the content and spatial distribution of water in inorganic glasses. Finds that the technique yields unique information, particularly in regard to spatial distribution, when compared with techniques of IR spectroscopy, SIMS, SIPS, NRRA, ESR and NMR. Points out that large areas (e.g., several square inches) of sample can be mapped in a single exposure. Notes that the spatial resolution of water in the glass network can be 10 -7 m, so very accurate diffusion profiles are obtainable

  15. Estrogen receptors in the temporomandibular joint of the baboon (Papio cynocephalus): an autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Aufdemorte, T.B.; Van Sickels, J.E.; Dolwick, M.F.; Sheridan, P.J.; Holt, G.R.; Aragon, S.B.; Gates, G.A.

    1986-04-01

    Using an autoradiographic method, the temporomandibular joint (TMJ) complex of five aged female baboons was studied for the presence of receptors for estradiol-17 beta. The study was performed in an effort to learn more of the pathophysiology of this joint and in an attempt to provide a scientific basis to explain the reported preponderance of women who seek and undergo treatment for signs and symptoms referable to the TMJ. This experiment revealed that the TMJ complex contains numerous cells with receptors for estrogen, particularly the articular surface of the condyle, articular disk, and capsule. Muscles of mastication contained relatively fewer receptors. As a result, one may postulate a role for the sex steroid hormones in the maintenance, repair, and/or pathogenesis of the TMJ. Additional studies are necessary to fully determine the significance of hormone receptors in this site and any correlation between diseases of the TMJ and the endocrine status of affected patients.

  16. Estrogen receptors in the temporomandibular joint of the baboon (Papio cynocephalus): an autoradiographic study

    International Nuclear Information System (INIS)

    Aufdemorte, T.B.; Van Sickels, J.E.; Dolwick, M.F.; Sheridan, P.J.; Holt, G.R.; Aragon, S.B.; Gates, G.A.

    1986-01-01

    Using an autoradiographic method, the temporomandibular joint (TMJ) complex of five aged female baboons was studied for the presence of receptors for estradiol-17 beta. The study was performed in an effort to learn more of the pathophysiology of this joint and in an attempt to provide a scientific basis to explain the reported preponderance of women who seek and undergo treatment for signs and symptoms referable to the TMJ. This experiment revealed that the TMJ complex contains numerous cells with receptors for estrogen, particularly the articular surface of the condyle, articular disk, and capsule. Muscles of mastication contained relatively fewer receptors. As a result, one may postulate a role for the sex steroid hormones in the maintenance, repair, and/or pathogenesis of the TMJ. Additional studies are necessary to fully determine the significance of hormone receptors in this site and any correlation between diseases of the TMJ and the endocrine status of affected patients

  17. Organization of ascending auditory pathways in the pigeon (Columba livia) as determined by autoradiographic methods

    International Nuclear Information System (INIS)

    Correia, M.J.; Eden, A.R.; Westlund, K.N.; Coulter, J.D.

    1982-01-01

    A mixture of tritiated proline and fucose was injected into the labyrinthine endolymphatic space of 5 white king pigeons (Columba livia). Using standard autoradiographic techniques, the authors observed transsynaptic labeling in ascending auditory pathways to the level of the mesencephalon. Auditory system structures, ipsilateral to the injection site, which labeled heavily were the cochlear nerve, the magnocellular and angular nuclei, and the superior olive. Those ipsilateral structures which were slightly labeled were the lateral lemniscus and the dorsal part of the lateral mesencephalic nucleus. Contralateral structures which labeled were the superior olive, lateral lemniscus, and dorsal part of the lateral mesencephalic nucleus. The results of this study suggest that ascending auditory pathways (to the level of mesencephalon) in the pigeon are more similar to those described for mammals in general than previously thought. (Auth.)

  18. Organization of ascending auditory pathways in the pigeon (Columba livia) as determined by autoradiographic methods

    Energy Technology Data Exchange (ETDEWEB)

    Correia, M.J.; Eden, A.R.; Westlund, K.N.; Coulter, J.D. (Texas Univ., Galveston (USA). Medical Branch)

    1982-02-25

    A mixture of tritiated proline and fucose was injected into the labyrinthine endolymphatic space of 5 white king pigeons (Columba livia). Using standard autoradiographic techniques, the authors observed transsynaptic labeling in ascending auditory pathways to the level of the mesencephalon. Auditory system structures, ipsilateral to the injection site, which labeled heavily were the cochlear nerve, the magnocellular and angular nuclei, and the superior olive. Those ipsilateral structures which were slightly labeled were the lateral lemniscus and the dorsal part of the lateral mesencephalic nucleus. Contralateral structures which labeled were the superior olive, lateral lemniscus, and dorsal part of the lateral mesencephalic nucleus. The results of this study suggest that ascending auditory pathways (to the level of mesencephalon) in the pigeon are more similar to those described for mammals in general than previously thought.

  19. Origin of the somatic cells in the rat gonad: An autoradiographic approach

    Energy Technology Data Exchange (ETDEWEB)

    Merchant-Larios, H [Departamento de Biologia del Desarrollo, Instituto de Investigaciones Biomedicas, Mexico City

    1979-01-01

    Gonads from rats of 11 and 12 days of gestation that had been given a pulse of /sup 3/H-thymidine were studied at different times using autoradiographic techniques. When the animals were labeled before the formation of the gonadal blastema (11 days), the percentage of labeled cells in this structure was greater than in the coelomic epithelium and mesenchyme. However, when /sup 3/H-thymidine was injected after the gonadal blastema was already established (12 days), very few of these cells took up the compound; they remained in this conditions until the sexual differentiation of the gonad. From this characteristic, which is an indication of the early differentiation of the blastemal cells, one may conclude that the seminiferous cords arise from this initial cellular line. On the other hand, there appears to be a contribution of coelomic epithelial cells during the formation of the sex cords in the ovary.

  20. Tissue distribution of epimucosally applied 3H DNFB: an autoradiographic study

    International Nuclear Information System (INIS)

    Warfvinge, G.; Larsson, Aa.

    1988-01-01

    The distribution of 3 H-labeled 2,4-dinitrofluorobenzene (DNFB) has been autoradiographically investigated in buccal mucosa after topical application to sensitized or nonsensitized rats. The rats were killed between 3 min and 24 h after challenge. No significant labeling pattern differences were found between plastic embedded and frozen sections. Surface epithelium was heavily labeled and labeled cells were observed in the lamina propria shortly (3-6 min) after application. These cells were clearly dendritic. Specific accumulation of hapten in epithelial Langerhans cells (LC) could not be clearly demonstrated. The connective tissue labeling gradually diminished and at 24 h post-elicitation, remaining label could be detected only in the epithelial surface layers. (author)

  1. An autoradiographic study of the projections of the central nucleus of the monkey amygdala

    International Nuclear Information System (INIS)

    Price, J.L.; Amaral, D.G.

    1981-01-01

    The efferent connections of the central nucleus of the monkey amygdala have been studied using the autoradiographic method for tracing axonal projections. Small injections of 3H-amino-acids which are largely confined to the central nucleus lead to the labeling of several brainstem nuclei as far caudally as the spinomedullary junction. A number of intra-amygdaloid connections between the basal and lateral nuclei of the amygdala and the central nucleus are also described. The present findings, taken together with recently reported widespread projections from the temporal association cortex to the amygdala, point out a potentially trisynaptic route between neocortical association regions and a variety of brainstem nuclei, many of which are related to autonomic function

  2. Autoradiographic localization of 131I-labelled thyroxine in the tissues of rat

    International Nuclear Information System (INIS)

    Prakash, P.; Romack, F.E.

    1977-01-01

    An attempt was made to visualize the sites of localization of 131 I-labelled thyroxine in the tissues of the rat by autoradiographic dipping techniques. The maximal uptake of 131 I-thyroxine in rats occured at 12 hours in all the tissues examined. The radioactivity continued to decrease from 12 to 36 hours after the injection. In the liver and kidney, the decline after 12 hours was rather marked. The radioactivity decreased only slightly from 12 to 36 hours in the spleen. After 3 hours of injection, the radioactivity was consistently higher in the thyroid follicular epithelial cells than in the interfollicular connective tissue. A high concentration of radioactivity was found at the periphery of the colloid areas. (author)

  3. Descriptive, cytochemical and autoradiographic data on the paranucleolar mass. Electron microscopic study in several Lacertilians

    International Nuclear Information System (INIS)

    Hubert, Jean

    1975-01-01

    In several Lacertilians, a nuclear fibrillar area, called paranucleolar mass in previous works, is a constant cytological feature of germ cells and certain somatic cells. This nuclear area shows many similarities with the nuclear area called in different animals nuclear vacuole, paranucleolar vacuole or light area. The ultrastructure and development of the paranucleolar mass is described. The cytochemical study indicates that it is composed of proteins. The autoradiographic results show that it does not incorporate thymidine 3 H or uridine 3 H, which is in agreement with the lack of DNA and RNA proved with cytochemical procedures. It is rarely labelled with leucine 3 H. This last result which seems to be at variance with the proteinaceous nature of the paranucleolar mass is probably due to our short experimental periods in proportion to the long formation of the paranucleolar mass [fr

  4. Autoradiographic measurement of Pu distribution in mixed-oxide nuclear fuel

    International Nuclear Information System (INIS)

    Green, D.R.; Rasmussen, D.E.; Gray, W.H.

    1976-09-01

    The autoradiographic method described was developed for rapid, economical determination of the Pu distribution and microhomogeneity in mixed oxide fuel. High Pu concentration regions of any size down to 13 microns in diameter can be reproducibly resolved using this method. The new method uses computerized scanning and analysis, and includes automatic self-calibration to virtually elimate variations resulting from photographic film and processing. The speed of this new method allows analysis of enough data to ensure statistical reliability of occurrence frequencies, even for sparse populations of Pu-rich regions with diameters greater than 60 microns. Determination of these occurrence frequencies is an important factor in controlling fuel quality to ensure safe, efficient operation in a Liquid Metal Fast Breeder Reactor

  5. Autoradiographic evidence of 2-methylindole covalent binding to pulmonary epithelial cells in the goat

    International Nuclear Information System (INIS)

    Becker, G.M.; Breeze, R.G.; Carlson, J.R.

    1984-01-01

    3-Methylindole (3MI), the main ruminal fermentation product of L-tryptophan, causes acute pulmonary edema and interstitial emphysema in ruminants. Intravenous infusion of 3MI in goats causes necrosis and sloughing of pneumocytes and bronchial epithelial cells. Previous studies indicate that a reactive metabolite or metabolites of 3MI bind covalently to tissue macromolecules in the lung and this binding is associated with the pneumotoxicity of 3MI. We undertook this autoradiographic study of 3MI covalent binding to test the hypothesis that reactive 3MI metabolite(s) bind to the lung cells susceptible to 3MI-induced injury. We infused goats with ( 3 H)3MI and killed them either 0.5, 2 or 6 h after start of the infusion. Sections of fixed lung were extensively washed, alcohol dehydrated and embedded in plastic. Only covalently bound radioactivity remained. Silver grains were quantitated per area in the developed autoradiographs. There was a 2:1 ratio of binding to the small airway epithelium compared to the interalveolar septa in all the goats. Both ciliated and non-ciliated bronchiolar cells were labelled, as were both types I and II pneumocytes. Normal goat lung slices incubated in vitro with ( 3 H)3MI were labeled in the same pattern. Inclusion of either of the inhibitors of cytochrome P-450, SKF-525-A or piperonyl butoxide significantly reduced this binding to both the pneumocytes and the bronchiolar cells. We consider these results supportive of our hypothesis that 3MI is metabolized to reactive intermediates by the epithelial cells of the lung, where they bind to macromolecules, which may cause cellular damage. (author)

  6. Effects of heavy-ion exposure to rat's hypothalamus on the copulatory behavior

    International Nuclear Information System (INIS)

    Saito, Masayoshi; Uno, Takashi; Kawata, Tetsuya; Liu, C.; Kan'o, Momoe; Okamura, Junko; Ito, Hisao; Takai, Nobuhiko; Ando, Koichi

    2006-01-01

    The present study was designed to determine whether irradiation (carbon particles 290 MeV/nucleon, Mono Peak 30-60 Gy, irradiation field 5 mm cube in hypothalamus) to hypothalamus modifies the copulatory behavior of male rats. By the second year, we studied the chronic effects for heavy ions on the copulatory behavior. In addition, the influence of heavy ions to cortex (irradiation field width and depth 5 mm, respectively) was studied. The copulatory items were recorded: frequency number of mounting, intromission and ejaculation during 30 min after 1, 3 and 6-7 months following irradiation. Results are as follows. At 60 Gy to hypothalamus, the frequency number of intromission and ejaculation was decreased from one month to 7 months following irradiation. Particularly, suppression for the copulatory behavior was recognized in 3 and 4 months after irradiation. At 3 and 4 months after 60 Gy irradiation, the frequency number of ejaculation was decreased in comparison with non-irradiated (control) male rats. At 45 Gy to hypothalamus or cortex, the frequency number of ejaculation was decreased after one month (Both sides of hypothalamus and cortex) and 3 months (Only as for hypothalamus) following irradiation. At 30 Gy to cortex, the frequency number of ejaculation was similar but irradiation to hypothalamus decreased it 3 months following irradiation. (author)

  7. Magnetic resonance imaging of hypothalamus hypophysis axis lesions

    International Nuclear Information System (INIS)

    Shiina, Takeki; Uno, Kimiichi; Arimizu, Noboru; Yoshida, Sho; Yamada, Kenichi.

    1990-01-01

    Magnetic resonance imaging (MRI) using a 0.5T superconductive machine was performed to the thirty three cases with a variety of the sellar and parasellar tumors and with dysfunction of the hypothalamus-hypophysis axis. Posterior pituitary bright spot (PBS) on T1 weighted image was evaluated with the pituitary hormonal function. These cases were 12 cases of post-treated tumors including pituitary adenoma (9 patients), suprasellar germinoma (2 patients) and craniopharyngioma (one patient), and non-tumorous conditions including 15 cases of central diabetes insipidus (DI), Syndrome of inappropriate secretion of ADH (SIADH) (one patient), Sheehan's syndrome (3 patients) and anorexia nervosa (2 patients). Pituitary bright spot was not seen in all 19 cases with overt DI. On the other hand, PBS was not seen in 9 cases without overt DI. Three cases of these 9 cases showing Sheehan's syndrome with insufficient antidiuretic hormone (ADH) secretion was considered as the state of subclinical DI. Posterior bright spot was not seen in all 13 cases of empty sella including partial empty sella. The results suggested that disappearance of PBS represents abnormality or loss of posterior pituitary function and also it was considered to be closely related to the empty sella. (author)

  8. A difference in [14C]deoxyglucose autoradiographic patterns in striate cortex between Macaca and Saimiri monkeys following monocular stimulation

    International Nuclear Information System (INIS)

    Hendrickson, A.E.; Wilson, J.R.

    1979-01-01

    Since the apparent absence of ocular dominance columns (ODC) in some New World primates could be caused by deficiencies of the transsynaptic autoradiographic technique, such as spillage of label in the poorly laminated dorsal lateral geniculate nucleus, the authors have examined this question using a functional autoradiographic tracing technique based on the uptake of [ 14 C]2-deoxyglucose ([ 14 C]dG) by active neurons. When only one eye is stimulated, this innovative method graphically demonstrates a repetitive pattern in Macaca monkey striate cortex which has been interpreted to be the ODC driven by the open eye. They now report on the results of a comparative study of Old World Macaca and New World Saimiri monkeys using [ 14 C]dG autoradiography in which evidence is found for repetitive patterns of [ 14 C]dG in Saimiri for layers above, but not in, layer IV. (Auth.)

  9. Activity changes of the cat paraventricular hypothalamus during phasic respiratory events

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Poe, G R; Rector, D M

    1997-01-01

    We monitored the spatiotemporal organization of cellular activity in the medial paraventricular hypothalamus during spontaneously-occurring periods of increased inspiratory effort followed by prolonged respiratory pauses (sigh/apnea) in the freely-behaving cat. Paraventricular hypothalamic activity...

  10. In vitro autoradiographic localization of vasoactive intestinal peptide (VIP) binding sites in the rat central nervous system

    International Nuclear Information System (INIS)

    Besson, J.; Dussaillant, M.; Marie, J.C.; Rostene, W.; Rosselin, G.

    1984-01-01

    This paper describes the autoradiographic distribution of VIP binding sites in the rat central nervous system using monoiodinated 125I-labeled VIP. High densities of VIP binding sites are observed in the granular layer of the dorsal dentate gyrus of the hippocampus, the basolateral amygdaloid nucleus, the dorsolateral and median geniculate nuclei of the thalamus as well as in the ventral part of the hypothalamic dorsomedial nucleus

  11. An autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

    International Nuclear Information System (INIS)

    Kasubuchi, Yasuo; Mino, Masahiro; Yoshioka, Hiroshi; Kusunoki, Tomoichi

    1979-01-01

    The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status. (author)

  12. Autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

    Energy Technology Data Exchange (ETDEWEB)

    Kasubuchi, Y; Mino, M; Yoshioka, H; Kusunoki, T [Kyoto Prefectural Univ. of Medicine (Japan)

    1979-10-01

    The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status.

  13. Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography

    International Nuclear Information System (INIS)

    Corp, E.S.; Woods, S.C.; Figlewicz, D.P.; Porte, D. Jr.; Baskin, D.G.; Dorsa, D.M.

    1986-01-01

    In vitro autoradiography and computer video densitometry were used to localize and quantify binding of 125 I-insulin in the hypothalamus of the rat brain. Highest specific binding was found in the arculate, dorsomedial, suprachiasmatic, paraventricular and periventricular regions. Significantly lower binding was present in the ventromedial nucleus and median eminence. The results are consistent with the hypothesis that insulin modulates the neural regulation of feeding by acting at sites in the hypothalamus. (author)

  14. Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia

    OpenAIRE

    Ihnatko, Robert; Post, Claes; Blomqvist, Anders

    2013-01-01

    Background: Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain’s metabolic control centre. Methods: The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed litterma...

  15. Slits Are Chemorepellents Endogenous to Hypothalamus and Steer Thalamocortical Axons into Ventral Telencephalon

    OpenAIRE

    Braisted, Janet E.; Ringstedt, Thomas; O'Leary, Dennis D. M.

    2009-01-01

    Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into...

  16. Autoradiographic study on the distribution of 241Am in the shell of the freshwater zebra mussel Dreissena polymorpha

    International Nuclear Information System (INIS)

    Zuykov, M.; Pelletier, E.; Rouleau, C.; Popov, L.; Fowler, S.W.; Orlova, M.

    2009-01-01

    Autoradiography was used to identify α-track distributions in a series of shell sections from live mussels Dreissena polymorpha Pallas and dissected shells of dead mussels obtained from laboratory experiments using relatively high concentrations of 241 Am in the exposure media, a required condition for successful use of this autoradiographic technique. A comparable distribution of α-tracks was recorded on autoradiographs from both live and dead shells suggesting that metabolism does not lead to any sizable changes in the process of 241 Am adsorption (present in the extrapallial fluid) onto the inner surface of shell. Autoradiographs showed a preferential accumulation of 241 Am in the organic periostracum, whereas the outer and inner shell layers were characterized by a relatively low α-tracks density. No α-tracks were observed in the central part of the shell in any of the samples. These observations will be useful for the development of a general model to explain bioaccumulation and biosorption processes of radionuclides into mollusk shells. (author)

  17. Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density?

    Directory of Open Access Journals (Sweden)

    Mi Jang

    2017-01-01

    Full Text Available BackgroundThe proportion of saturated fatty acids/unsaturated fatty acids in the diet seems to act as a physiological regulation on obesity, cardiovascular diseases, and diabetes. Differently composed fatty acid diets may induce satiety of the hypothalamus in different ways. However, the direct effect of the different fatty acid diets on satiety in the hypothalamus is not clear.MethodsThree experiments in mice were conducted to determine whether: different compositions of fatty acids affects gene mRNA expression of the hypothalamus over time; different types of fatty acids administered into the stomach directly affect gene mRNA expression of the hypothalamus; and fat composition changes in the diet affects gene mRNA expression of the hypothalamus.ResultsThe type of fat in cases of purified fatty acid administration directly into the stomach may cause changes of gene expressions in the hypothalamus. Gene expression by dietary fat may be regulated by calorie amount ingested rather than weight amount or type of fat.ConclusionTherefore, the calorie density factor of the diet in regulating hypothalamic gene in food intake may be detrimental, although the possibility of type of fat cannot be ruled out.

  18. Chromium VI administration induces oxidative stress in hypothalamus and anterior pituitary gland from male rats.

    Science.gov (United States)

    Nudler, Silvana I; Quinteros, Fernanda A; Miler, Eliana A; Cabilla, Jimena P; Ronchetti, Sonia A; Duvilanski, Beatriz H

    2009-03-28

    Hexavalent chromium (Cr VI)-containing compounds are known carcinogens which are present in industrial settings and in the environment. The major route of chromium exposure for the general population is oral intake. Previously we have observed that Cr VI affects anterior pituitary secretion and causes oxidative stress in vitro. The aim of the present work was to investigate if in vivo Cr VI treatment (100 ppm of Cr VI in drinking water for up 30 days) causes oxidative stress in hypothalamus and anterior pituitary gland from male rats. This treatment produced a 4-fold increase of chromium content in hypothalamus and 10-fold increase in anterior pituitary gland. Lipid peroxidation showed a significant increase in hypothalamus and anterior pituitary. Cr VI augmented superoxide dismutase activity in anterior pituitary gland and glutathione reductase activity in hypothalamus, but glutathione peroxidase and catalase activities remained unchanged in both tissues. Heme oxygenase-1 mRNA expression significantly rose in both tissues. Metallothionein 1 mRNA content increased in anterior pituitary and metallothionein 3 mRNA increased in hypothalamus. These results show, for the first time, that oral chronic administration of Cr VI produces oxidative stress on the hypothalamus and anterior pituitary gland which may affect normal endocrine function.

  19. Effect of low dose radiation on POMC transcription level in mouse hypothalamus and immune organs

    International Nuclear Information System (INIS)

    Wan Hong; Liu Shuzheng

    1998-01-01

    Objective: To disclose the changes in mRNA transcription level of POMC in the hypothalamus and immune organs after low dose radiation. Method: In situ hybridization was used to examine the changes of POMC mRNA transcription level in mouse hypothalamus and immune organs following whole body irradiation (WBI) with 75 mGy X-rays. Results: There was a basal expression of POMC mRNA in both the hypothalamus and immune organs. POMC mRNA-positive neutron were located in the arcuate nucleus of hypothalamus. WBI with 75 mGy X-rays could significantly down-regulate the POMC transcription level that was remarkable within 1h and remained low in the observation period of 12h. POMC transcription level in mouse immune organs increased with time within 8h after irradiation and then began to decrease but still remained at a higher than normal level. The changes of POMC transcription level were more marked in the spleen than in other immune organs. Conclusion: These findings suggest that the immediate decrease of POMC transcription level in the hypothalamus might be the direct cause of the down-regulation of the hypothalamus-pituitary-adrenocortical axis after WBI with 75 mGy X-rays, accompanied with an increase in POMC transcription in immune organs

  20. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    Science.gov (United States)

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Autoradiographic analysis of tritiated imipramine binding in the human brain post mortem: effects of suicide

    International Nuclear Information System (INIS)

    Gross-Isseroff, R.; Israeli, M.; Biegon, A.

    1989-01-01

    In vitro quantitative autoradiography of high-affinity tritiated imipramine binding sites was performed on brains of 12 suicide victims and 12 matched controls. Region-specific differences in imipramine binding were found between the two groups. Thus, the pyramidal and molecular layers of the cornu ammoni hippocampal fields and the hilus of the dentate gyrus exhibited 80%, 60%, and 90% increases in binding in the suicide group, respectively. The postcentral cortical gyrus, insular cortex, and claustrum had 45%, 28%, and 75% decreases in binding in the suicide group, respectively. No difference in imipramine binding was observed in prefrontal cortical regions, in the basal ganglia, and in mesencephalic nuclei. No sex and postmortem delay effects on imipramine binding were found. Imipramine binding was positively correlated with age, the effect of age being most pronounced in portions of the basal ganglia and temporal cortex

  2. Autoradiographic localization of a gluten peptide during organ culture of human duodenal mucosa

    International Nuclear Information System (INIS)

    Fluge, G.; Aksnes, L.

    1983-01-01

    An 125I-labeled subfraction of Frazer's fraction III (molecular weight, 8,000) was added to the culture medium during organ culture of duodenal biopsies from two patients with celiac disease in exacerbation. The isotope-labeled gluten peptide was localized by autoradiography after 6, 12, and 24 h of culture. At 6 h, labeling was located mainly in the basal layers of the biopsies. The tissue was well preserved. After 12 h in culture, the labeling had spread to the lamina propria and the crypts. A few grains were located over enterocytes and desquamated cells. Moderate histological signs of toxicity were observed. After 24 h, there was marked toxic deterioration, comparable to that seen after culture with alpha-gliadin. Labeling had spread throughout the entire section. There seemed to be no specificity of the binding, for the entire section was affected. Culture with the identical gluten fraction, in the radionegative state, produced histological deterioration comparable to that seen after exposure to the isotope-labeled peptide. Gluten peptides are presented to the target cells in a unique way during organ culture, different from in vivo conditions. This may influence the results when the organ culture method is used to investigate the pathogenesis of celiac disease

  3. Autoradiographic visualization of extrajunctional acetylcholine receptors in whole human biceps brachii muscle

    International Nuclear Information System (INIS)

    Askmark, H.; Gillberg, P.-G.; Aquilonius, S.-M.

    1985-01-01

    The morphological distribution of acetylcholine receptors in the whole biceps brachii muscle from a patient with amyotrophic lateral sclerosis (ALS) and from a control patient was studied by in vitro autoradiography with 3 H-alpha-bungarotoxin alphaBtx). In ALS, 3 H-alpha-Btx binding occurred over the entire muscle, while in the control case the binding was restricted to the motor end-plate region. (author)

  4. Autoradiographic localization of a gluten peptide during organ culture of human duodenal mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Fluge, G.; Aksnes, L.

    1983-01-01

    An 125I-labeled subfraction of Frazer's fraction III (molecular weight, 8,000) was added to the culture medium during organ culture of duodenal biopsies from two patients with celiac disease in exacerbation. The isotope-labeled gluten peptide was localized by autoradiography after 6, 12, and 24 h of culture. At 6 h, labeling was located mainly in the basal layers of the biopsies. The tissue was well preserved. After 12 h in culture, the labeling had spread to the lamina propria and the crypts. A few grains were located over enterocytes and desquamated cells. Moderate histological signs of toxicity were observed. After 24 h, there was marked toxic deterioration, comparable to that seen after culture with alpha-gliadin. Labeling had spread throughout the entire section. There seemed to be no specificity of the binding, for the entire section was affected. Culture with the identical gluten fraction, in the radionegative state, produced histological deterioration comparable to that seen after exposure to the isotope-labeled peptide. Gluten peptides are presented to the target cells in a unique way during organ culture, different from in vivo conditions. This may influence the results when the organ culture method is used to investigate the pathogenesis of celiac disease.

  5. The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent

    Directory of Open Access Journals (Sweden)

    Sutcliffe Margaret

    2011-04-01

    Full Text Available Abstract Background Humans and mice with loss of function mutations in GPR54 (KISS1R or kisspeptin do not progress through puberty, caused by a failure to release GnRH. The transcriptional networks regulated by these proteins in the hypothalamus have yet to be explored by genome-wide methods. Results We show here, using 1 million exon mouse arrays (Exon 1.0 Affymetrix and quantitative polymerase chain reaction (QPCR validation to analyse microdissected hypothalamic tissue from Gpr54 and Kiss1 knockout mice, the extent of transcriptional regulation in the hypothalamus. The sensitivity to detect important transcript differences in microdissected RNA was confirmed by the observation of counter-regulation of Kiss1 expression in Gpr54 knockouts and confirmed by immunohistochemistry (IHC. Since Gpr54 and Kiss1 knockout animals are effectively pre-pubertal with low testosterone (T levels, we also determined which of the validated transcripts were T-responsive and which varied according to genotype alone. We observed four types of transcriptional regulation (i genotype only dependent regulation, (ii T only dependent regulation, (iii genotype and T-dependent regulation with interaction between these variables, (iv genotype and T-dependent regulation with no interaction between these variables. The results implicate for the first time several transcription factors (e.g. Npas4, Esr2, proteases (Klk1b22, and the orphan 10-transmembrane transporter TMEM144 in the biology of GPR54/kisspeptin function in the hypothalamus. We show for the neuronal activity regulated transcription factor NPAS4, that distinct protein over-expression is seen in the hypothalamus and hippocampus in Gpr54 knockout mice. This links for the first time the hypothalamic-gonadal axis with this important regulator of inhibitory synapse formation. Similarly we confirm TMEM144 up-regulation in the hypothalamus by RNA in situ hybridization and western blot. Conclusions Taken together, global

  6. Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the anx/anx mouse model.

    Science.gov (United States)

    Mercader, Josep Maria; Lozano, Juan José; Sumoy, Lauro; Dierssen, Mara; Visa, Joana; Gratacòs, Mònica; Estivill, Xavier

    2008-11-12

    The anx/anx mouse displays poor appetite and lean appearance and is considered a good model for the study of anorexia nervosa. To identify new genes involved in feeding behavior and body weight regulation we performed an expression profiling in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected 156 differentially expressed genes and validated 92 of those using TaqMan low-density arrays. The expression of a set of 87 candidate genes selected based on literature evidences was also quantified by TaqMan low-density arrays. Our results showed enrichment in deregulated genes involved in cell death, cell morphology, and cancer, as well as an alteration of several signaling circuits involved in energy balance including neuropeptide Y and melanocortin signaling. The expression profile along with the phenotype led us to conclude that anx/anx mice resemble the anorexia-cachexia syndrome typically observed in cancer, infection with human immunodeficiency virus or chronic diseases, rather than starvation, and that anx/anx mice could be considered a good model for the treatment and investigation of this condition.

  7. Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction.

    Science.gov (United States)

    Bellefontaine, Nicole; Chachlaki, Konstantina; Parkash, Jyoti; Vanacker, Charlotte; Colledge, William; d'Anglemont de Tassigny, Xavier; Garthwaite, John; Bouret, Sebastien G; Prevot, Vincent

    2014-06-01

    The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonadotropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalamo-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region.

  8. Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

    Science.gov (United States)

    Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

    1996-04-01

    Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

  9. Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C]iodoantipyrine technique in freely moving rats

    International Nuclear Information System (INIS)

    Nehlig, A.; Pereira de Vasconcelos, A.; Boyet, S.

    1989-01-01

    The postnatal changes in local cerebral blood flow in freely moving rats were measured by means of the quantitative autoradiographic [ 14 C]iodoantipyrine method. The animals were studied at 10, 14, 17, 21 and 35 days and at the adult stage. At 10 days after birth, rates of blood flow were very low and quite homogeneous in most cerebral structures except in a few posterior areas. From these relatively uniform levels, values of local cerebral blood flow rose notably to reach a peak at 17 days in all brain regions studied. Rates of blood flow decreased between 17 and 21 days after birth and then increased from weaning time to reach the known characteristic distribution of the adult rat. The postnatal evolution of local cerebral blood in the rat is in good agreement with previous studies in other species such as dog and humans that also show higher rates of cerebral blood flow and glucose utilization at immature stages. However, in the rat, local cerebral blood flow and local cerebral glucose utilization are not coupled over the whole postnatal period studied, since blood flow rates reach peak values at 17 days whereas glucose utilization remains still quite low at that stage. The high rate of cerebral blood flow in the 17-day-old rat may reflect the energetic and biosynthetic needs of the actively developing brain that are completed by the summation of glucose and ketone body utilization

  10. Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster

    International Nuclear Information System (INIS)

    Lucky, A.W.; Eisenfeld, A.J.; Visintin, I.

    1985-01-01

    In the hamster flank organ, the growth of hair and growth of sebaceous glands are androgen-dependent functions. Although dihydrotestosterone (DHT) is known to be a potent stimulator of flank organ growth, there is no information about localization of DHT receptor sites in this organ. The purpose of this study was to use steroid autoradiography to localize DHT receptors in the hamster flank organ. Because steroid hormones are functional when translocated to nuclear receptors, nuclear localization by autoradiography defines receptor sites. In order to be able to visualize autoradiographic grains from radiolabeled androgens around hair follicles, albino hamsters were studied to avoid confusion between the grains and pigment granules which are abundant in the more common Golden Syrian hamster. Mature male hamsters castrated 24 hours earlier were given tritium-labeled dihydrotestosterone ( [ 3 H]DHT). Using the technique of thaw-mount steroid autoradiography, 4-micron unfixed frozen sections were mounted in the dark onto emulsion-coated glass slides and allowed to develop for 4-6 months. [ 3 H]DHT was found to be concentrated over sebocyte nuclei. The label was present peripherally as well as in differentiating sebocytes. There was no nuclear localization of [ 3 H]DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of [ 3 H] DHT were assessed by thin-layer chromatography in paired tissue samples. Most of the label remained with DHT. Uptake was inhibited in the flank organ of hamsters pretreated with unlabeled DHT

  11. Autoradiographic determination of catechol estrogen binding sites in brain, pituitary and uterus

    International Nuclear Information System (INIS)

    Parvizi, N.; Sar, M.; Duncan, G.E.; Stumpf, W.E.

    1985-01-01

    The anatomical pattern of nuclear binding of 2-OH[6,9- 3 H]estradiol ([ 3 H]2-OHE 2 ) in brain, pituitary and uterus have been studied autoradiographically. Autoradiograms of forebrain, pituitary and uterus show nuclear concentrations of radioactivity in certain cells. This nuclear concentration is abolished when unlabelled 2-OHE 2 or E 2 was injected prior to the injection of [ 3 H]2-OHE 2 . In the brain nuclear labelling is observed in the septal-preoptic region, in the anterior hypothalamic area, and in the central hypothalamic area. Some estrogen-sensitive nuclear groups, such as lateral septum and hippocampus, do not show accumulation of radioactivity. In the uterus, luminal and glandular epithelium, stromal cell and muscle cells are labelled. A comparison of the quantitative nuclear uptake of radioactivity and of the different time intervals after the injection of different doses shows similar uptake of nuclear radioactivity. This is comparable to data obtained after [6,7- 3 H]estradiol ([ 3 H]E 2 ) injection. The results provide clear evidence for nuclear binding of catechol estrogens of the same magnitude as [ 3 H]E 2 after in vivo treatment. (Auth.).0

  12. Autoradiographic disposition of [1-methyl-14C]- and [2-14C]caffeine in mice

    International Nuclear Information System (INIS)

    Lachance, M.P.; Marlowe, C.; Waddell, W.J.

    1983-01-01

    Male, C57B1/6J mice received either [1-methyl-14C]caffeine or [2-14C]caffeine via the tail vein at a dose of 0.7 or 11 mg/kg, respectively. At 0.1, 0.33, 1, 3, 9, and 24 hr after treatment, the mice were anesthetized with ether and frozen by immersion in dry ice/hexane. The mice were processed for whole-body autoradiography by the Ullberg technique; this procedure does not allow thawing or contact with solvents. All autoradiographs revealed some retention of radioactivity at early time intervals in the lacrimal glands, seminal vesicle fluid, nasal and olfactory epithelium, and retinal melanocytes. The remaining portion of the animal was densitometrically uniform except for the lower levels noted in the CNS and adipose tissues. Excretion of radioactivity by the liver and kidneys seems to be the major routes of elimination. Localization in the liver at late time intervals was confined principally to the centrilobular region. Late sites of retention, observed only after [1-methyl-14C]caffeine administration, included the pancreas, minor and major salivary glands, splenic red pulp, thymal cortex, bone marrow, and gastrointestinal epithelium. Sites of localization present in both studies included the olfactory epithelium, lacrimal glands, hair follicles, and retinal melanocytes. Further studies are needed to determine whether the localization at these various sites is due to metabolic degradation, active transport, or possibly a specific receptor interaction

  13. Autoradiographic studies of chromosome replication during the cell cycle of Streptococcus faecium

    International Nuclear Information System (INIS)

    Higgins, M.L.; Koch, A.L.; Dicker, D.T.; Daneo-Moore, L.

    1986-01-01

    Analysis of the distribution of autoradiographic grains around cells of Streptococcus faecium which had been either continuously or pulse-labeled with tritiated thymidine (mass doubling time, 90 min) showed a non-Poisson distribution even when the distribution of cell sizes in the populations studied was taken into account. These non-Poisson distributions of grains were assumed to reflect the discontinuous nature of chromosome replication. To study this discontinuous process further, an equation was fitted to the grain distribution observed for the pulse-labeled cells that assumed that in any population of cells there were subpopulations in which there were zero, one, or two replicating chromosomes. This analysis predicted an average time for chromosome replication and for the period between completion of rounds of chromosome replication and division of 55 and 43 min, respectively, which were in excellent agreement with estimates made by other techniques. The present investigation extended past studies in indicating that the initiation and completion of rounds of chromosome replication are poorly phased with increases in cell volume and that the amount of chromosome replication may be different in different cell halves

  14. A study on measurement of the regional cerebral blood flow using autoradiographic method in moyamoya disease

    International Nuclear Information System (INIS)

    Sasaki, Tomohiro; Kiya, Katsuzo; Yuki, Kiyoshi; Kawamoto, Hitoshi; Mizoue, Tatsuya; Kiura, Yoshihiro; Uozumi, Tohru; Ikawa, Fusao

    1997-01-01

    Development of Autoradiographic method (ARG) has provided measurement of cerebral blood flow in moyamoya disease. We evaluate a cerebral vasodilatory capacity (CVC) for moyamoya disease using ARG method. We used 5 patients with moyamoya disease as a candidate for measurement of the cerebral blood flow (CBF) who admitted to Hiroshima Prefectural Hospital during the past one year. There were 3 patients in an adult age and 2 patients in a young age. We tried to measure the regional CBF (rCBF) using ARG method which was a easy way to estimate the rCBF on SPECT. The CVC was calculated from the difference of the rCBF between resting SPECT and Diamox-loading SPECT. Results were as follows; Reactivity of cerebral vessels to CO 2 loading and CVC weakened in moyamoya disease. The rCBF and CVC in the territories of anterior and middle cerebral arteries reduced in comparison with those in the area supplied by the posterior cerebral artery. The CVC at the treated side with surgical reconstruction recovered somewhat in an adult type. From these results, measurement of CBF using ARG method seems to be useful for evaluation of the CVC in moyamoya disease. (author)

  15. Thiazide diuretic receptors: Autoradiographic localization in rat kidney with [3H]metolazone

    International Nuclear Information System (INIS)

    Beaumont, K.; Vaughn, D.A.; Healy, D.P.

    1989-01-01

    The localization of binding sites for [ 3 H]metolazone, a quinazolinesulfonamide diuretic with thiazide-like actions, was determined by in vitro autoradiography. [ 3 H]Metolazone bound saturably to rat kidney sections incubated in vitro with a dissociation constant (Kd) = 3.4 nM and binding site density = 0.14 pmol/mg of protein. Incubation conditions were used that excluded binding to low affinity sites and carbonic anhydrase. Pharmacological specificity of binding was consistent with labeling of physiologically relevant thiazide diuretic receptors, as identified in previous studies of [ 3 H]metolazone binding to renal membranes. Autoradiographs obtained with tritium-sensitive film demonstrated that binding sites were limited to the renal cortex and were relatively sparsely distributed. Higher resolution autoradiography indicated that [ 3 H] metolazone binding sites were localized in a highly specific manner over short lengths of tubular segments, which by their morphology and distribution most likely represented distal convoluted tubules. In the short sections of tubule that contained receptors, labeling was very dense and appeared to be more prevalent over luminal than peritubular surfaces. The intrarenal distribution of [ 3 H]metolazone binding sites provides further evidence for their identity as thiazide diuretic receptors. These results are consistent with physiological studies demonstrating that the early distal tubule is the location of thiazide-sensitive sodium chloride cotransport

  16. Quantitative autoradiographic analysis of muscarinic receptor subtypes and their role in representational memory

    International Nuclear Information System (INIS)

    Messer, W.S.

    1986-01-01

    Autoradiographic techniques were used to examine the distribution of muscarinic receptors in rat brain slices. Agonist and selective antagonist binding were examined by measuring the ability for unlabeled ligands to inhibit [ 3 H]-1-QNB labeling of muscarinic receptors. The distribution of high affinity pirenzepine binding sites (M 1 subtype) was distinct from the distribution of high affinity carbamylcholine sites, which corresponded to the M 2 subtype. In a separate assay, the binding profile for pirenzepine was shown to differ from the profile for scopolamine, a classical muscarinic antagonist. Muscarinic antagonists, when injected into the Hippocampus, impaired performance of a representational memory task. Pirenzepine, the M 1 selective antagonist, produced representational memory deficits. Scopolamine, a less selective muscarinic antagonist, caused increases in running times in some animals which prevented a definitive interpretation of the nature of the impairment. Pirenzepine displayed a higher affinity for the hippocampus and was more effective in producing a selective impairment of representational memory than scopolamine. The data indicated that cholinergic activity in the hippocampus was necessary for representation memory function

  17. Double-label autoradiographic deoxyglucose method for sequential measurement of regional cerebral glucose utilization

    Energy Technology Data Exchange (ETDEWEB)

    Redies, C; Diksic, M; Evans, A C; Gjedde, A; Yamamoto, Y L

    1987-08-01

    A new double-label autoradiographic glucose analog method for the sequential measurement of altered regional cerebral metabolic rates for glucose in the same animal is presented. This method is based on the sequential injection of two boluses of glucose tracer labeled with two different isotopes (short-lived /sup 18/F and long-lived /sup 3/H, respectively). An operational equation is derived which allows the determination of glucose utilization for the time period before the injection of the second tracer; this equation corrects for accumulation and loss of the first tracer from the metabolic pool occurring after the injection of the second tracer. An error analysis of this operational equation is performed. The double-label deoxyglucose method is validated in the primary somatosensory (''barrel'') cortex of the anesthetized rat. Two different rows of whiskers were stimulated sequentially in each rat; the two periods of stimulation were each preceded by an injection of glucose tracer. After decapitation, dried brain slices were first exposed, in direct contact, to standard X-ray film and then to uncoated, ''tritium-sensitive'' film. Results show that the double-label deoxyglucose method proposed in this paper allows the quantification and complete separation of glucose utilization patterns elicited by two different stimulations sequentially applied in the same animal.

  18. Registration and three-dimensional reconstruction of autoradiographic images by the disparity analysis method

    International Nuclear Information System (INIS)

    Zhao, Weizhao; Ginsberg, M.; Young, T.Y.

    1993-01-01

    Quantitative autoradiography is a powerful radio-isotopic-imaging method for neuroscientists to study local cerebral blood flow and glucose-metabolic rate at rest, in response to physiologic activation of the visual, auditory, somatosensory, and motor systems, and in pathologic conditions. Most autoradiographic studies analyze glucose utilization and blood flow in two-dimensional (2-D) coronal sections. With modern digital computer and image-processing techniques, a large number of closely spaced coronal sections can be stacked appropriately to form a three-dimensional (3-d) image. 3-D autoradiography allows investigators to observe cerebral sections and surfaces from any viewing angle. A fundamental problem in 3-D reconstruction is the alignment (registration) of the coronal sections. A new alignment method based on disparity analysis is presented which can overcome many of the difficulties encountered by previous methods. The disparity analysis method can deal with asymmetric, damaged, or tilted coronal sections under the same general framework, and it can be used to match coronal sections of different sizes and shapes. Experimental results on alignment and 3-D reconstruction are presented

  19. A unit density method of grain analysis used to identify GABEergic neurons for electron microscopic autoradiographs

    International Nuclear Information System (INIS)

    Burry, R.W.

    1982-01-01

    The distribution of electron microscopic autoradiographic grains over neurons in cerebellar cultures incubated with [ 3 H]gamma-aminobutyric acid ([ 3 H]GABA) was examined. With the unit density method of grain analysis, the number of grains over each structure was tested against the total grain density for the entire section. If an individual structure has a grain density higher than the expected grain density, it is considered one of the group of heavily labeled structures. The expected grain density for each structure is calculated based on the area for that structure, the total grain density and the Poisson distribution. A different expected grain density can be calculated for any P value required. The method provides an adequate population of structures for morphological analysis but excludes weakly labeled structures and thus may underestimate the number of labeled structures. The unit density method of grain analysis showed, as expected, a group of cell bodies and synapses that was labeled heavily. Cultures incubated with other [ 3 H]amino acids did not have any heavily labeled synaptic elements. In addition, serial section analysis of sections showed that synapses heavily labeled with [ 3 H]GABA are seen in adjacent sections. The advantage of the unit density method of grain analysis is that it can be used to separate two groups of metabolically different neurons even when no morphological differences are present. (Auth.)

  20. Autoradiographic localization of mu and delta opioid receptors in the mesocorticolimbic dopamine system

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P. Jr.

    1989-01-01

    In vitro autoradiographic techniques were coupled with selective chemical lesions of the A10 dopamine cells and intrinsic perikarya of the region to delineate the anatomical localization of mu and delta opioid receptors, as well as, neurotensin receptors. Mu opioid receptors were labeled with {sup 125}I-DAGO. Delta receptors were labeled with {sup 125}I-DPDPE. Neurotensin receptors were labeled with {sup 125}I-NT3. Unilateral lesions of the dopamine perikarya were produced by injections of 6-OHDA administered in the ventral mesencephalon. Unilateral lesions of intrinsic perikarya were induced by injections of quinolinic acid in to the A10 dopamine cell region. Unilateral lesions produced with 6-OHDA resulted in the loss of neurotensin receptors in the A10 region and within the terminal fields. Mu opioid receptors were unaffected by this treatment, but delta opioid receptors increased in the contralateral striatum and nucleus accumbens following 6-OHDA administration. Quinolinic acid produced a reduction of mu opioid receptors within the A10 region with a concomitant reduction in neurotensin receptors in both the cell body region and terminal fields. These results are consistent with a variety of biochemical and behavioral data which suggest the indirect modulation of dopamine transmission by the opioids. In contrast these results strongly indicate a direct modulation of the mesolimbic dopamine system by neurotensin.

  1. Follicle and oocyte growth in early postnatal calves: cytochemical, autoradiographical and electron microscopical studies

    International Nuclear Information System (INIS)

    Mhawi, A.J.; Kaňka, J.; Motlík, J.

    1991-01-01

    The initiation of oocyte and follicle growth was studied in 1- and 3-d-old calf ovaries using cytochemical, autoradiographical and electron microscopical approaches. Attention was only paid to unilaminar ovarian follicles that were classified into 3 categories: unilaminar flattened (UF), unilaminar flatto-cuboidal (UFC) and unilaminar cuboidal (UC) ovarian follicles when the oocyte was surrounded by 1 layer of flattened, a mixture of flattened and cuboidal and entirely cuboidal follicle cells, respectively. Our findings suggested that oocytes within each of these follicle categories were in different developmental stages. Furthermore, electron microscopic observations revealed that early after birth, oocyte nuclei characteristic of diplotene configuration (aggregation of the nuclear chromatin into moderately electron-dense small patches and fibrillo-granular texture of the nucleolus) were encountered in 41% of the UF follicles. The rest of the UF as well as all of the UFC and UC follicles were found to contain dictyate oocytes in which the chromatin was highly decondensed and the nucleolus differentiated into fibrillar, fibrillo-granular and granular components. The present results also indicated that the complete transition of the surrounding follicle cells from flattened to cuboidal shape and the morphological changes of the oocyte endoplasmic reticulum and mitochondria were 2 complementary events essential for initiation of oocyte growth

  2. DNA synthesis and pronucleus development in pig zygotes obtained in vivo: an autoradiographic and ultrastructural study

    International Nuclear Information System (INIS)

    Laurincik, J.; Hyttel, P.; Kopecny, V.

    1995-01-01

    Porcine zygotes flushed from oviducts 48, 52, 56, 60, or 64 hr after hCG were incubated 30 min in 3H-thymidine, transferred to nonradioactive medium for 2 hr, and incubated for 30 min with 14C-thymidine. After this procedure, ova were prepared (i.e., at 51, 55, 59, 63, or 67 hr after hCG) for autoradiography and ultrastructural observations, respectively. The first autoradiographic labelling, i.e., DNA synthesis, was observed at 56-56.5 hr after hCG, while the latest labelling was seen at 60-60.5 hr. At 51 hr after hCG, formation of the pronuclear envelope was observed, while no nucleolus precursor bodies or prestages to these structures were found. At 55 hr a few clusters of small electron-dense granules were observed, together with condensed chromatin in the pronuclei. At 59 hr the apposed regions of both pronuclei contained nucleolus precursor bodies and condensed chromatin, in close contact with both clusters of small granules and clusters of an additional category of large granules and the nuclear envelope. Additionally, large accumulations of the small granules were found in the vicinity of similarly sized accumulations of the large granules without chromatin association. At 63 hr the spherical accumulations of large granules on some occasions presented a central vacuole, and condensed chromatin and clusters of small granules were attached to its periphery. Within the vacuole, electron-dense material was found

  3. Autoradiographic studies of the adaptative behaviour of the oral flora to xylit

    International Nuclear Information System (INIS)

    Schmidt, R.

    1980-01-01

    Fasten saliva samples of 22 test persons were aerobically incubed with radio-labeled xylit and sorbit for 24 hours at 37 0 C. It was determined by thin-layer chromatography and by the autoradiographic detection of the sugar alcohols, after what incubation time the sugar substitutes were completely metabolised. In order to provide intensive contact between the organisms of the oral cavity and the xylit the test persons rinsed their mouth three times per day with a xylit solution over a period of one month. Then a second saliva sample was examined. By adding the bacteriostaticum chloramphenicol to the cultures, it was proved that in the majority of the test persons the decompensation of xylit and sorbit is enzymatically induced when the organisms living in the oral cavity get into contact with sugar alcohol. Between the decompensation time before and after 30 days of xylit contact no significant difference could be found. These results permit the conclusion that after the contact over one month the organisms of the oral cavity do not adapt to xylit. (orig./MG) [de

  4. Autoradiographic assay of mutants resistant to diphtheria toxin in mammalian cells in vitro

    International Nuclear Information System (INIS)

    Ronen, A.; Gingerich, J.D.; Duncan, A.M.V.; Heddle, J.A.

    1984-01-01

    Diptheria toxin kills mammalian cells by ribosylating elongation factor 2, a protein factor necessary for protein synthesis. The frequency of cells able to form colonies in the presence of the toxin can be used as an assay for mutation to diphtheria toxin resistance. Resistance to diphtheria toxin can also be detected autoradiographically in cells exposed to [ 3 H]leucine after treatment with the toxin. In cultures of Chinese hamster ovary cells, the frequency of such resistant cells is increased by exposure of the cells to γ-rays, ultraviolet light, ethylnitrosourea, mitomycin c, ethidium bromide, and 5-bromo-2'-deoxyuridine in a dose- and time-dependent manner. The resistant cells form discrete microcolonies if they are allowed to divide several times before intoxication which indicates that they are genuine mutants. The assay is potentially adaptable to any cell population that can be intoxicated with diphtheria toxin and labeled with [ 3 H]leucine, whether or not the cells can form colonies. It may be useful, therefore, for measuring mutation rates in slowly growing or nondividing cell populations such as breast, brain, and liver, as well as in cells that do divide but cannot be readily cloned, such as the colonic epithelium. 23 references, 6 figures

  5. An autoradiographic method of mapping the distribution and density of monoamine neurons in mouse brain

    International Nuclear Information System (INIS)

    Masuoka, D.T.; Alcaraz, A.F.

    1975-01-01

    A combined in vitro uptake and autoradiographic procedure as an important complement to the histochemical fluorescence method is described. Slabs of fresh mouse brain were incubated with 14 C-NE, 14 C-DA or 14 C-5-HT, freeze-dried, and placed against X-ray film for autoradiography. Catecholamine nerve terminals were labeled by in vitro incubation with 14 C-NE or 14 C-DA. Dopaminergic terminals were labeled by 14 C-NE incubation preceded by desipramine (to block uptake into NE terminals). With 14 C-5-HT incubation, the uptake pattern indicated the possibility that 5-HT nerve terminals were being labeled. Advantages of this method are that it allows the visualization of overall density and distribution of selected monoamine nerve terminals or uptake sites of other putative neurotransmitters in whole coronal or sagittal sections, so that data are obtained from many areas of brain or spinal cord rather than in only those areas preselected for microscopic viewing

  6. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

    Science.gov (United States)

    St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

    2011-01-01

    To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  7. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland

    Directory of Open Access Journals (Sweden)

    Jonny eSt-Amand

    2012-01-01

    Full Text Available To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the mouse hypothalamus, pituitary gland and parietal cortex using serial analysis of gene expression (SAGE. Total counts of SAGE tags for the hypothalamus, pituitary gland and parietal cortex were 165824, 126688 and 161045 tags, respectively. This represented 59244, 45151 and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis and turnover, cell differentiation, the cell cycle and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  8. Hypothalamus-Anchored Resting Brain Network Changes before and after Sertraline Treatment in Major Depression

    Directory of Open Access Journals (Sweden)

    Rui Yang

    2014-01-01

    Full Text Available Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n=12 both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.

  9. Effect of gamma irradiation on the activity of monoamine oxidase in the hypothalamus of ewes

    International Nuclear Information System (INIS)

    Pastorova, B.; Stanikova, A.

    2008-01-01

    The study investigated changes in monoamine oxidase (MAO) activity in the hypothalamus of ewes in the anoestrous period exposed to a whole body Co-60 irradiation with a total dose of 6.7 Gy for the period of 7 days. The activity of MAO was determined by means of a radiochemical method using C-14 tryptamine as a substrate. Whole body exposure to gamma radiation of total dose of 6.7 Gy increased significantly (P < 0.001) the activity of MAO in the caudal, medial and rostral hypothalamus of the investigated ewes. It may by assumed that an increased degradation of catecholamines caused by MAO is one of the mechanisms responsible for pronounced changes in the level of catecholamines in the hypothalamus of ewes after irradiation. (authors)

  10. Study on the interaction between leucine-enkephalin and hypothalamus-pituitary-thyroid axis

    International Nuclear Information System (INIS)

    Li Fengying; Chen Jialun; Chen Mingdao; Tang Jinfeng; Li Jiping

    2001-01-01

    Objective: To study the possible interaction between leucine enkephalin and hypothalamus-pituitary-thyroid axis. Methods: Mice models of hyperthyroidism and hypothyroidism were produced. Serum thyroid hormonal levels (T 3 , T 4 , TSH, TRH), the leucine enkephalin content of the whole brain and 5-HT of the hypothalamus were determined in the animals sacrificed on different days after the animal models were established. Results: In hyperthyroid rats, the levels of T 3 , T 4 increased progressively (P 3 , T 4 levels were persistent lower (P < 0.001) along with gradually increasing of serum TSH and TRH levels while pituitary TSh hypothalamus TRH content decreased gradually (P < 0.01), but rose back when reaching the nadir, Besides, LEK elevated and 5-HT decreased (P<0.01). Conclusion: The thyroid functional hormonal changes are not necessarily accompanied by a corresponding increase or decrease of brain LEK

  11. Detection, Quantification, and Microlocalisation of Targets of Pesticides Using Microchannel Plate Autoradiographic Imagers

    Directory of Open Access Journals (Sweden)

    Mabruka H. Tarhoni

    2011-10-01

    Full Text Available Organophosphorus (OP compounds are a diverse chemical group that includes nerve agents and pesticides. They share a common chemical signature that facilitates their binding and adduction of acetylcholinesterase (AChE within nerve synapses to induce cholinergic toxicity. However, this group diversity results in non-uniform binding and inactivation of other secondary protein targets, some of which may be adducted and protein activity influenced, even when only a relatively minor portion of tissue AChE is inhibited. The determination of individual OP protein binding targets has been hampered by the sensitivity of methods of detection and quantification of protein-pesticide adducts. We have overcome this limitation by the employment of a microchannel plate (MCP autoradiographic detector to monitor a radiolabelled OP tracer compound. We preincubated rat thymus tissue in vitro with the OP pesticides, azamethiphos-oxon, chlorfenvinphos-oxon, chlorpyrifos-oxon, diazinon-oxon, and malaoxon, and then subsequently radiolabelled the free OP binding sites remaining with 3H-diisopropylfluorophosphate (3H-DFP. Proteins adducted by OP pesticides were detected as a reduction in 3H-DFP radiolabelling after protein separation by one dimensional polyacrylamide gel electrophoresis and quantitative digital autoradiography using the MCP imager. Thymus tissue proteins of molecular weights ~28 kDa, 59 kDa, 66 kDa, and 82 kDa displayed responsiveness to adduction by this panel of pesticides. The 59 kDa protein target (previously putatively identified as carboxylesterase I was only significantly adducted by chlorfenvinphos-oxon (p < 0.001, chlorpyrifos-oxon (p < 0.0001, and diazinon-oxon (p < 0.01, the 66 kDa protein target (previously identified as serum albumin similarly only adducted by the same three pesticides (p < 0.0001, (p < 0.001, and (p < 0.01, and the 82 kDa protein target (previously identified as acyl peptide hydrolase only adducted by chlorpyrifos-oxon (p

  12. Catecholamine levels in sheep hypothalamus, hypophysis and adrenals following whole-body gamma irradiation

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.; Molnarova, M.

    1985-01-01

    Changes were studied in the levels of catecholamines and L-DOPA in the control system of the reproduction cycle (hypothalamus, hypophysis) and in the adrenal glands of sheep after whole-body irradiation with 60 Co at a total dose of 6.7 Gy for seven days. The output of the radiation source was 0.039 Gy/h. The catecholamines (noradrenaline, dopamine and adrenaline) and L-DOPA were determined after separation from the tissues by the method of spectral fluorometry. After whole-body exposure to gamma radiation, noradrenaline dropped in the hypothalamus in comparison with the control group, most significantly in the rostral (by 74.2%) and caudal (by 40%) parts. A similar drop was also observed in dopamine, the concentrations of which decreased in the rostral hypothalamus by 60%. Adrenaline showed a drop in the hypothalamus, most significant in the caudal region (by 62%). Consequently, the level of the precursor of the synthesis of catecholamines and L-DOPA changed and showed in the studied regions of the hypothalamus significantly lower levels than in the control group. As regards the hypophysis, after irradiation no significant changes in the levels of noradrenaline and adrenaline were recorded, however, dopamine and L-DOPA dropped significantly (P<0.01). The exposure to gamma radiation also causes a decrease in the concentrations of catecholamines and L-DOPA in the adrenal glands of sheep, most significantly in noradrenaline (by 61%). It was thus found that whole-body irradiation of sheep with a dose of 6.7 Gy results in a significant decrease in the level of catecholamines in the hypothalamus, hypophysis and adrenal glands, which is probably in relation to the failure of synthesis and degradation of catecholamines and to the total organism injury

  13. Autoradiographic investigation of the removal of non-metallic inclusions in connection with the steel remelting process in vacuum furnaces

    International Nuclear Information System (INIS)

    Kolaski, H.; Siewierski, J.

    1978-01-01

    The labelled radioactive non-metallic inclusions in steel were obtained through deoxidation of steel with an activated aluminium alloy containing 1% rare earths. Quantity and distribution of the non-metallic inclusions in the steel were determined by applying autoradiography to the longitudinal and cross sections of the steel slabs. After remelting in an electronic furnace the distribution of non-metallic inclusions was determined by autoradiography of the lateral surfaces and the cross section of the slabs. It was found that 50 - 70% of the inclusions could be removed. The results obtained from autoradiographic investigation allow the exploration of the mechanism of the removal of inclusions. (author)

  14. Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study

    International Nuclear Information System (INIS)

    Watanabe, Arata; Nakai, Akio; Tohyama, Yoshihiro; Nguyen, Khnah Q.; Diksic, Mirko

    2006-01-01

    Anpirtoline has been described as an agonist at 5-HT 1B receptors with a relatively high potency. It also acts as an agonist at 5-HT 1A receptors, but has a lower potency than at the 5-HT 1B sites. There is very little known about the mechanism by which anpirtoline influences regional 5-HT synthesis. The aim of the present study was to investigate the effects of acutely and chronically administered anpirtoline on 5-HT synthesis in the rat brain using the autoradiographic α-[ 14 C]methyl-L-tryptophan method. In the acute study, anpirtoline (2.0 mg/kg) was administered intraperitoneally 30 min before the tracer injection. The control rats were injected with the same volume of saline. In the chronic study, anpirtoline (2 mg/kg per day) was injected subcutaneously in saline once a day for 10 days. There were no significant differences between the plasma-free and total tryptophan concentrations between the anpirtoline treatment and the respective control groups. In the acute experiment, 5-HT synthesis rates in all of the brain areas investigated were significantly decreased by anpirtoline when compared to the saline-treated group. In the chronic anpirtoline experiment, 5-HT synthesis rates of almost all of the projection areas, as well as the raphe nuclei, were normalized or had a tendency to be normalized. These results suggest that it is likely that the terminal 5-HT 1B receptors are involved in the regulation of 5-HT synthesis in the projection areas and that 5-HT synthesis, in the raphe, is likely influenced by anpirtoline's 5-HT 1A and/or 5-HT 1B agonistic properties

  15. Autoradiographic study of gamma-irradiated mouse spleen during primary immune response

    International Nuclear Information System (INIS)

    Gitsov, L.G.; Kyncheva, L.S.; Burneva, V.G.; Martinova, J.Sh.; Viklichka, S.

    1978-01-01

    Study on the kinetics of the cells in the mouse spleen during the primary immune response against thymusdependent antigen after sublethal irradiation was carried out. For this purpose the animals were immunized with sheep erythrocytes one day after their irradiation with 700 r gamma rays. On the 5th day after the immunization, tritium labelled thymidine was injected three times at two hourly intervals. Mice were killed two hours after the third injection for preparation of routine histological samples and autoradiographs. Immunized, but not irradiated mice were utilized as controls. Extensive zones of lymphocyte destruction were observed in the spleen of the irradiated mice - accumulation of picnotic lymphocyte nuclei, surrounded by reticulo-histocyte elements. The number of the labelled cells and the intensity of labelled are lower than that of the germinal centres in control animal. There is no marked cell destruction in the periarteriolar zone nor labelled cells, whereas in the controls there is a considerable number of labelled blast cells. In the red pulp of the irradiated animals islands of erythroblasts were found, whereas in the controls - parallely to the erythroblast islands, there are islands of proliferating lymphocytes and plasmocytes. The decrease of lymphocyte number in irradiated mice is connected with their destruction and with the altered lymphocytopoiesis in the red pulp. It is assumed that the observed preservation of the periarteriolar lymphatic sheaths in an expression of a higher radioresistance of the T-cells as compared to the B-cells in the white pulp. This study contributes for elucidation of the irradiation immunosuppressive effect. It points out also that the post-irradiation lymphopaenia is due not only to the cell death but also to the exclusion of part of the T-lymphocytes from the circulation and their selective deposition in the thymus-dependent zones of the peripheral lymphoid organs. (A.B.)

  16. Heterogeneity of uridine incorporation along the rabbit nephron. I. Autoradiographic study

    International Nuclear Information System (INIS)

    Vandewalle, A.; Farman, N.; Cluzeaud, F.; Bonvalet, J.P.

    1984-01-01

    An autoradiographic study of uridine labeling in tubular segments microdissected from the rabbit kidney is presented. Kidney pyramids were incubated for 60 min with low (66 nM) and high (66μM) [ 3 H]-uridine concentration. At the two concentrations studied the labeling was almost exclusively nuclear in all segments studied. At the low concentration, labeling predominated in the macula densa (MD = 63.88 +/- 6.15 silver grains/100 μm 2 , n = 11), cortical ascending limb (CAL = 19.65 +/- 1.65, n = 15), and initial distal tubule (DCT/sub a/ = 24.31 +/- 2.70, n = 6). It was minimal in the proximal tubule (PCT 2 = 9.14 +/- 1.61, n = 16) and in the cortical (CCT = 5.23 +/- 0.75, n = 18) and medullary (MCT = 5.52 +/- 1.10, n = 12) collecting ducts. At a high concentration, the profile of labeling was roughly similar except for a relative increase in labeling much more pronounced in collecting ducts (CCT = +373, MCT = +323%) than in the other structures (MD = -14, CAL = +66, DCT/sub a/ = +49, PCT = +9%). Pulse-chase experiments do not show evidence for differences in turnover or degradation rates of RNA between segments, at least in the PCT and the connecting part of the CCT. Analysis of the results at low and high concentration suggests that the observed heterogeneity in uridine labeling depends on both variable endogenous nucleoside pools and different rates of uridine incorporation into RNA from one segment to another

  17. Heterogeneity of uridine incorporation along the rabbit nephron. I. Autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Vandewalle, A.; Farman, N.; Cluzeaud, F.; Bonvalet, J.P.

    1984-04-01

    An autoradiographic study of uridine labeling in tubular segments microdissected from the rabbit kidney is presented. Kidney pyramids were incubated for 60 min with low (66 nM) and high (66..mu..M) (/sup 3/H)-uridine concentration. At the two concentrations studied the labeling was almost exclusively nuclear in all segments studied. At the low concentration, labeling predominated in the macula densa (MD = 63.88 +/- 6.15 silver grains/100 ..mu..m/sup 2/, n = 11), cortical ascending limb (CAL = 19.65 +/- 1.65, n = 15), and initial distal tubule (DCT/sub a/ = 24.31 +/- 2.70, n = 6). It was minimal in the proximal tubule (PCT/sub 2/ = 9.14 +/- 1.61, n = 16) and in the cortical (CCT = 5.23 +/- 0.75, n = 18) and medullary (MCT = 5.52 +/- 1.10, n = 12) collecting ducts. At a high concentration, the profile of labeling was roughly similar except for a relative increase in labeling much more pronounced in collecting ducts (CCT = +373, MCT = +323%) than in the other structures (MD = -14, CAL = +66, DCT/sub a/ = +49, PCT = +9%). Pulse-chase experiments do not show evidence for differences in turnover or degradation rates of RNA between segments, at least in the PCT and the connecting part of the CCT. Analysis of the results at low and high concentration suggests that the observed heterogeneity in uridine labeling depends on both variable endogenous nucleoside pools and different rates of uridine incorporation into RNA from one segment to another.

  18. In vivo binding and autoradiographic imaging of (+)-3-[125I]Iodo-MK-801 to the NMDA receptor-channel complex in rat brain

    International Nuclear Information System (INIS)

    Gibson, R.E.; Burns, H.D.; Thorpe, H.H.; Waisi Eng; Ransom, R.; Solomon, H.

    1992-01-01

    Radioiodinated (+)-3-Iodo-MK-801 is a high affinity radioligand for the N-methyl-D-aspartate (NMDA) receptor-channel complex. We have demonstrated in vivo localization in the CNS of rat which is stereoselective and blocked by coinjection of unlabeled MK-801. Autoradiography indicates localization in vivo which is in concordance with in vitro autoradiographic studies. These results indicate that radioiodinated (+)-3-Iodo-MK-801 is a useful probe for in vitro and in vivo autoradiographic studies and suggest that radioligands for the NMDA receptor may be developed which will provide in vivo images of receptor distribution in man. (author)

  19. A Newly Defined Area of the Mouse Anterior Hypothalamus Involved in Septohypothalamic Circuit: Perifornical Area of the Anterior Hypothalamus, PeFAH.

    Science.gov (United States)

    Horii-Hayashi, Noriko; Nishi, Mayumi

    2018-02-27

    Although the hypothalamus is classified into more than 10 compartments, it still contains uncharacterized areas. In this study, we identified a new triangular-shaped area between the paraventricular hypothalamic nucleus (PVN) and the fornix area in the mouse anterior hypothalamus, which is enriched in chondroitin sulfate proteoglycans (CSPGs). We designated this region as the perifornical area of the anterior hypothalamus (PeFAH) based on its anatomical location. As evidenced by Nissl staining, the PeFAH was distinguishable as an area of relatively low density. Immunohistochemical and DNA microarray analyses indicated that PeFAH contains sparsely distributed calretinin-positive neurons and densely clustered enkephalin-positive neurons. Furthermore, the PeFAH was shown to have bidirectional neural connections with the lateral septum. Indeed, we confirmed enkephalinergic projections from PeFAH neurons to the lateral septum, and inversely, calbindin-positive lateral septum neurons as afferents to the PeFAH. Finally, c-Fos expression analysis revealed that the activity of certain PeFAH neuronal populations tended to be increased by psychological stressors, but not that of enkephalinergic neurons. We proposed PeFAH as a new region in the AH.

  20. Optogenetic activation of leptin- and glucose-regulated GABAergic neurons in dorsomedial hypothalamus promotes food intake via inhibitory synaptic transmission to paraventricular nucleus of hypothalamus

    Directory of Open Access Journals (Sweden)

    Zesemdorj Otgon-Uul

    2016-08-01

    Full Text Available Objective: The dorsomedial hypothalamus (DMH has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY, cocaine- and amphetamine-regulated transcript (CART, cholecystokinin (CCK, leptin receptor, and melanocortin 3/4 receptors. However, the principal neurons generating the orexigenic function in the DMH remain to be defined. This study aimed to clarify the role of the DMH GABAergic neurons in feeding regulation by using optogenetics and electrophysiological techniques. Methods: We generated the mice expressing ChRFR-C167A, a bistable chimeric channelrhodopsin, selectively in GABAergic neurons of DMH via locally injected adeno-associated virus 2. Food intake after optogenetic activation of DMH GABAergic neurons was measured. Electrophysiological properties of DMH GABAergic neurons were measured using slice patch clamp. Results: Optogenetic activation of DMH GABAergic neurons promoted food intake. Leptin hyperpolarized and lowering glucose depolarized half of DMH GABAergic neurons, suggesting their orexigenic property. Optical activation of axonal terminals of DMH GABAergic neurons at the paraventricular nucleus of hypothalamus (PVN, where anorexigenic neurons are localized, increased inhibitory postsynaptic currents on PVN neurons and promoted food intake. Conclusion: DMH GABAergic neurons are regulated by metabolic signals leptin and glucose and, once activated, promote food intake via inhibitory synaptic transmission to PVN. Keywords: Dorsomedial hypothalamus, GABAergic neuron, Feeding, Leptin, Glucose, Optogenetics

  1. Evolution of hypothalamus-pituitary growth axis among fish, amphibian, birds and mammals

    Directory of Open Access Journals (Sweden)

    Moaeen-Ud-Din M.

    2015-01-01

    Full Text Available Hypothalamus-pituitary growth axis (HP growth axis regulates animal growth and development in pre-natal and post natal life governed by many factors. However, until recently, the evolutionary history of this axis among lineages is not understood. Aim of the present study was to understand the major events in evolution and evolutionary history and trend of HP growth axis. The diversity among Homo sapience, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio and Xenopus laevis was determined for genes involved in HP growth axis in current study. Sequences of HP growth axis genes were retrieved from NCBI (http://www.ncbi.nlm.nih.gov/. Nucleotide diversity using Kimura’s two-parameter method; codon-based test of positive selection using the Nei-Gojobori; equality of evolutionary rate with Tajima's relative rate test and phylogenetic history using the RelTime method were estimated in MEGA6. Estimates of the coefficients of evolutionary differentiation based on nucleotides and amino acids substitution patterns of HP growth axis genes showed contrasting evolutionary patterns among the lineages. The results demonstrated that although these genes might have crucial functional roles in each of the species, however, their sequence divergence did not necessarily reflect similar molecular evolution among the species. Codon-based test of positive selection revealed that Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat had similar and higher non synonymous substitutions (P > 0.05. Higher rate of non-synonymous substitutions at similar orthologs level among species indicated a similar positive selection pressure in these species. Results for relative rate test assessed with the chi-squared test showed difference on unique mutations among lineages at synonymous and non synonymous sites except Chicken vs Mouse, Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat. This indicated that the mutagenic process that generates

  2. Radiosynthesis and autoradiographic evaluation of [{sup 11}C]NAD-299, a radioligand for visualization of the 5-HT{sub 1A} receptor

    Energy Technology Data Exchange (ETDEWEB)

    Sandell, Johan E-mail: Johan.Sandell@psyk.ks.se; Halldin, Christer; Hall, Haakan; Thorberg, Seth-Olov; Werner, Tom; Sohn, Daniel; Sedvall, Goeran; Farde, Lars

    1999-02-01

    The selective 5-HT{sub 1A} receptor antagonist NAD-299 ([R]-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide) was labeled with the positron emitting radionucldie carbon-11. The radioligand was synthesized from NAD-195 ([R]-3-N,N-dicyclobutylamino-8-fluoro-5-trifluoromethylsulfonyloxy-3, 4-dihydro-2H-1-benzopyran) in two radiochemical steps. A palladium-catalyzed reaction of NAD-195 and [{sup 11}C]cyanide was followed by hydrolysis of the carbon-11-labeled nitrile intermediate with basic hydrogen peroxide. The total radiochemical yield, based on [{sup 11}C]CO{sub 2} and corrected for decay, was 20-40%. The specific radioactivity was 24 GBq/{mu}mol (900 Ci/mmol) at end of synthesis, with a radiochemical purity better than 99% and a total synthesis time of 40-45 min. Autoradiographic examination of [{sup 11}C]NAD-299 binding in human brain postmortem demonstrated high binding in hippocampus, raphe nuclei, and neocortex. The binding in the hippocampus was higher than in the neocortex. Within the hippocampus, the densest binding was observed in the CA1 region. [{sup 11}C]NAD-299 binding was inhibited by addition of the 5-HT{sub 1A} receptor ligands WAY-100635, pindolol, ({+-})-8-OH-DPAT, 5-HT, and buspirone, leaving a low background of nonspecific binding. The results indicate that [{sup 11}C]NAD-299 binds specifically to 5-HT{sub 1A} receptors in the human brain in vitro and is a potential radioligand for positron emission tomography (PET) examination of 5-HT{sub 1A} receptors in vivo.

  3. Radiosynthesis and autoradiographic evaluation of [11C]NAD-299, a radioligand for visualization of the 5-HT1A receptor

    International Nuclear Information System (INIS)

    Sandell, Johan; Halldin, Christer; Hall, Haakan; Thorberg, Seth-Olov; Werner, Tom; Sohn, Daniel; Sedvall, Goeran; Farde, Lars

    1999-01-01

    The selective 5-HT 1A receptor antagonist NAD-299 ([R]-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide) was labeled with the positron emitting radionucldie carbon-11. The radioligand was synthesized from NAD-195 ([R]-3-N,N-dicyclobutylamino-8-fluoro-5-trifluoromethylsulfonyloxy-3, 4-dihydro-2H-1-benzopyran) in two radiochemical steps. A palladium-catalyzed reaction of NAD-195 and [ 11 C]cyanide was followed by hydrolysis of the carbon-11-labeled nitrile intermediate with basic hydrogen peroxide. The total radiochemical yield, based on [ 11 C]CO 2 and corrected for decay, was 20-40%. The specific radioactivity was 24 GBq/μmol (900 Ci/mmol) at end of synthesis, with a radiochemical purity better than 99% and a total synthesis time of 40-45 min. Autoradiographic examination of [ 11 C]NAD-299 binding in human brain postmortem demonstrated high binding in hippocampus, raphe nuclei, and neocortex. The binding in the hippocampus was higher than in the neocortex. Within the hippocampus, the densest binding was observed in the CA1 region. [ 11 C]NAD-299 binding was inhibited by addition of the 5-HT 1A receptor ligands WAY-100635, pindolol, (±)-8-OH-DPAT, 5-HT, and buspirone, leaving a low background of nonspecific binding. The results indicate that [ 11 C]NAD-299 binds specifically to 5-HT 1A receptors in the human brain in vitro and is a potential radioligand for positron emission tomography (PET) examination of 5-HT 1A receptors in vivo

  4. Persistent expression of activated notch in the developing hypothalamus affects survival of pituitary progenitors and alters pituitary structure.

    Science.gov (United States)

    Aujla, Paven K; Bogdanovic, Vedran; Naratadam, George T; Raetzman, Lori T

    2015-08-01

    As the pituitary gland develops, signals from the hypothalamus are necessary for pituitary induction and expansion. Little is known about the control of cues that regulate early signaling between the two structures. Ligands and receptors of the Notch signaling pathway are found in both the hypothalamus and Rathke's pouch. The downstream Notch effector gene Hes1 is required for proper pituitary formation; however, these effects could be due to the action of Hes1 in the hypothalamus, Rathke's pouch, or both. To determine the contribution of hypothalamic Notch signaling to pituitary organogenesis, we used mice with loss and gain of Notch function within the developing hypothalamus. We demonstrate that loss of Notch signaling by conditional deletion of Rbpj in the hypothalamus does not affect expression of Hes1 within the posterior hypothalamus or expression of Hes5. In contrast, expression of activated Notch within the hypothalamus results in ectopic Hes5 expression and increased Hes1 expression, which is sufficient to disrupt pituitary development and postnatal expansion. Taken together, our results indicate that Rbpj-dependent Notch signaling within the developing hypothalamus is not necessary for pituitary development, but persistent Notch signaling and ectopic Hes5 expression in hypothalamic progenitors affects pituitary induction and expansion. © 2015 Wiley Periodicals, Inc.

  5. Double-radionuclide autoradiographic method using N-isopropyl-iodoamphetamine for sequential measurements of local cerebral blood flow

    International Nuclear Information System (INIS)

    Obrenovitch, T.P.; Clayton, C.B.; Strong, A.J.

    1987-01-01

    A double-radionuclide autoradiographic method has been assessed for sequential determinations of local CBF (LCBF). It is based on two successive intravascular injections of N-isopropyl-p-iodoamphetamine (IMP) labelled with different radionuclides, whose concentrations can later be differentiated in the same tissue section using double-radionuclide autoradiography. Previous studies suggested that the distribution of IMP, up to 30 min after its administration, still represents LCBFs. Our data indicate that, provided the tracer is injected directly into the left ventricle, there is little back diffusion from normal brain to blood under physiological conditions for at least 35 min following the tracer injection and an injection of unlabelled IMP, in a dose larger than that used for blood flow determination, does not displace any labelled IMP previously taken up by the brain, nor does it displace any labelled IMP previously accumulated in the lung that would lead to secondary brain uptake. On the basis of these results, we conclude that sequential autoradiographic determinations of LCBF using IMP labelled with different radionuclides is possible. This is a promising experimental method for the simultaneous investigation of changes in LCBF in several CNS structures

  6. Effects of HPM irradiation on expression of GR in hypothalamus and pituitary gland of rats

    International Nuclear Information System (INIS)

    Meng Li; Peng Ruiyun; Gao Yabing; Ma Junjie; Wang Shuiming; Hu Wenhua; Wang Dewen; Su Zhentao

    2005-01-01

    Objective: To explore the expression and significance of glucocorticoid receptor (GR) in hypothalamus and pituitary gland of rats after high power microwave (HPM) exposure. Methods: A total of 130 male Wistar rats were sacrificed at 6 h, 1 d, 3 d, 7 d, 14 d, 28 d and 3 m after whole body irradiation by 2-90 mW/cm 2 HPM and their hypothalamus and pituitary gland were collected. The changes of GR in the two tissues after HPM exposure were investigated by means of immunohistochemical staining and image analysis. Results: The expression of GR in hypothalamus was decreased after HPM exposure. The level of GR in the group of 10 mW/cm 2 was significantly lower (P 2 group was significantly lower (P 2 group was significantly higher (P 2 group was significantly higher (P<0.01) on 1 d and 3 d after HPM exposure. Conclusion: The expression of GR in hypothalamus was decreased while that in the anterior pituitary was increased after HPM exposure. The refore, the negative feedback of hypothalamic-pituitary-adrenal (HPA) axis was upset and the changes of GR is involved in the pathophysiological course of HPA. (authors)

  7. GABAergic projections from lateral hypothalamus to paraventricular hypothalamic nucleus promote feeding

    Science.gov (United States)

    Lesions of the lateral hypothalamus (LH) cause hypophagia. However, activation of glutamatergic neurons in LH inhibits feeding. These results suggest a potential importance for other LH neurons in stimulating feeding. Our current study in mice showed that disruption of GABA release from adult LH GAB...

  8. Influence of internal exposure on the morphofunctional characteristics of hypothalamus, pituitary and adrenal gland

    International Nuclear Information System (INIS)

    Derev'yanko, L.P.; Nosov, A.T.

    2004-01-01

    The phase changes in morphofunctional states of hypothalamus, pituitary, cortex and medulla of adrenal gland of rats, which for a long time (9 month) were fed a 137 Cs diary, were determined. At early stages of experiment (7 - 30 days) the enhancing of morphofunctional and secretory activity of cells of hypothalamus, pituitary, cortex and medulla of adrenal gland cells, were observed (total absorbed doses of 0,3 sGy). After 9 months (total absorbed doses of 3,0 sGy) in cells of hypothalamus, pituitary, cortex and medulla of adrenal gland the progressions of dystrophic-destructive changes of intracellular structures with the sings of decreasing of morphofunctional and secretory activities were determined. It is necessary to underline, that the sings of intracellular reparative regeneration, were observed in a small part of cells against the background of presence of dystrophic-destructive changes. In spite of the processes of intracellular reparative regeneration which were observed 9 months later after exposure, the completely renewing of morphofunctional and secretory activities in cells of hypothalamus, pituitary, cortex and medulla of adrenal gland cells were absent

  9. The role of gut hormones and the hypothalamus in appetite regulation.

    Science.gov (United States)

    Suzuki, Keisuke; Simpson, Katherine A; Minnion, James S; Shillito, Joyceline C; Bloom, Stephen R

    2010-01-01

    The World Health Organisation has estimated that by 2015 approximately 2.3 billion adults will be overweight and more than 700 million obese. Obesity is associated with an increased risk of diabetes, cardiovascular events, stroke and cancer. The hypothalamus is a crucial region for integrating signals from central and peripheral pathways and plays a major role in appetite regulation. In addition, there are reciprocal connections with the brainstem and higher cortical centres. In the arcuate nucleus of the hypothalamus, there are two major neuronal populations which stimulate or inhibit food intake and influence energy homeostasis. Within the brainstem, the dorsal vagal complex plays a role in the interpretation and relaying of peripheral signals. Gut hormones act peripherally to modulate digestion and absorption of nutrients. However, they also act as neurotransmitters within the central nervous system to control food intake. Peptide YY, pancreatic polypeptide, glucagon-like peptide-1 and oxyntomodulin suppress appetite, whilst ghrelin increases appetite through afferent vagal fibres to the caudal brainstem or directly to the hypothalamus. A better understanding of the role of these gut hormones may offer the opportunity to develop successful treatments for obesity. Here we review the current understanding of the role of gut hormones and the hypothalamus on food intake and body weight control.

  10. Optimization of viral vector technology to study gene function in the hypothalamus

    NARCIS (Netherlands)

    de Backer, M.W.A.

    2010-01-01

    The neural circuits involved in energy homeostasis are complex and include multiple brain regions and neuropeptides. The many functions of the different neuropeptide systems in the hypothalamus have been described; however, the specific roles of the different neuropeptides in specific hypothalamic

  11. Insulin in the arcuate nucleus of the hypothalamus reduces fat consumption in rats

    NARCIS (Netherlands)

    van Dijk, G; de Groote, C; Chavez, M; van der Werf, Y; Steffens, AB; Strubbe, JH

    1997-01-01

    Data are accumulating that insulin acting in the central nervous system is a physiological regulator of food intake and body weight, presumably via its effect in the hypothalamus. The present study investigated whether infusion of a small dose of insulin into two major hypothalamic insulin-binding

  12. 60 YEARS OF NEUROENDOCRINOLOGY: The structure of the neuroendocrine hypothalamus: the neuroanatomical legacy of Geoffrey Harris.

    Science.gov (United States)

    Watts, Alan G

    2015-08-01

    In November 1955, Geoffrey Harris published a paper based on the Christian A Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore, MD, USA. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing so, Harris introduced a set of properties that helped define the neuroendocrine hypothalamus. They included: i) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; ii) an analogy between the representation of body parts in the sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and iii) the idea that neuroendocrine neurons are motor neurons and the pituitary stalk functions as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons must pass in order to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries that were being made in the early 1950s were beginning to influence neuroendocrinology? This Thematic Review discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and, within this framework, how novel and powerful techniques are currently taking our understanding of the structure of the neuroendocrine hypothalamus to new levels. © 2015 Society for Endocrinology.

  13. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

    International Nuclear Information System (INIS)

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P.

    1990-01-01

    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of [35S]cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of [35S]cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, [35S]cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes

  14. Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.

    Science.gov (United States)

    Marshall, P E; Goldsmith, P C

    1980-07-14

    The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.

  15. Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus

    DEFF Research Database (Denmark)

    Rowe, Glenn C; Vialou, Vincent; Sato, Kazusa

    2012-01-01

    ) whether these effects were due to antagonism to AP1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ¿FosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass...

  16. Genome-wide DNA methylation analysis of the porcine hypothalamus-pituitary-ovary axis

    DEFF Research Database (Denmark)

    Yuan, Xiao Long; Zhang, Zhe; Li, Bin

    2017-01-01

    Previous studies have suggested that DNA methylation in both CpG and CpH (where H = C, T or A) contexts plays a critical role in biological functions of different tissues. However, the genome-wide DNA methylation patterns of porcine hypothalamus-pituitary-ovary (HPO) tissues remain virtually unex...

  17. A semi-automated algorithm for hypothalamus volumetry in 3 Tesla magnetic resonance images.

    Science.gov (United States)

    Wolff, Julia; Schindler, Stephanie; Lucas, Christian; Binninger, Anne-Sophie; Weinrich, Luise; Schreiber, Jan; Hegerl, Ulrich; Möller, Harald E; Leitzke, Marco; Geyer, Stefan; Schönknecht, Peter

    2018-07-30

    The hypothalamus, a small diencephalic gray matter structure, is part of the limbic system. Volumetric changes of this structure occur in psychiatric diseases, therefore there is increasing interest in precise volumetry. Based on our detailed volumetry algorithm for 7 Tesla magnetic resonance imaging (MRI), we developed a method for 3 Tesla MRI, adopting anatomical landmarks and work in triplanar view. We overlaid T1-weighted MR images with gray matter-tissue probability maps to combine anatomical information with tissue class segmentation. Then, we outlined regions of interest (ROIs) that covered potential hypothalamus voxels. Within these ROIs, seed growing technique helped define the hypothalamic volume using gray matter probabilities from the tissue probability maps. This yielded a semi-automated method with short processing times of 20-40 min per hypothalamus. In the MRIs of ten subjects, reliabilities were determined as intraclass correlations (ICC) and volume overlaps in percent. Three raters achieved very good intra-rater reliabilities (ICC 0.82-0.97) and good inter-rater reliabilities (ICC 0.78 and 0.82). Overlaps of intra- and inter-rater runs were very good (≥ 89.7%). We present a fast, semi-automated method for in vivo hypothalamus volumetry in 3 Tesla MRI. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. 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

  19. [Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

    Science.gov (United States)

    Sánchez-Criado, J E

    1979-06-01

    The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

  20. Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

    Science.gov (United States)

    Yan, Zhiyi; Jiao, Haiyan; Ding, Xiufang; Ma, Qingyu; Li, Xiaojuan; Pan, Qiuxia; Wang, Tingye; Hou, Yajing; Jiang, Youming; Liu, Yueyun; Chen, Jiaxu

    2018-05-03

    Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

  1. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

    Science.gov (United States)

    Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

    2017-10-15

    Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

  2. Visualization of μ1 opiate receptors in rat brain by using a computerized autoradiographic subtraction technique

    International Nuclear Information System (INIS)

    Goodman, R.R.; Pasternak, G.W.

    1985-01-01

    The authors have developed a quantitative computerized subtraction technique to demonstrate in rat brain the regional distribution of μ 1 sites, a common very-high-affinity binding site for both morphine and the enkephalins. Low concentrations of [D-Ala 2 , D-Leu 5 ]enkephalin selectively inhibit the μ 1 binding of [ 3 H]dihydromorphine, leaving μ 2 -sites, while low morphine concentrations eliminate the μ 1 binding of [ 3 H][D-Ala 2 , D-Leu 5 ]enkephalin, leaving sigma sites. Thus, quantitative differences between images of sections incubated in the presence and absence of these low concentrations of unlabeled opioid represent μ 1 binding sites. The regional distributions of μ 1 sites labeled with [ 3 H]dihydromorphine were quite similar to those determined by using [ 3 H][D-Ala 2 , D-Leu 5 ]enkephalin. High levels of μ 1 binding were observed in the periaqueductal gray, medial thalamus, and median raphe, consistent with the previously described role of μ 1 sites in analgesia. Other regions with high levels of μ 1 binding include the nucleus accumbens, the clusters and subcallosal streak of the striatum, hypothalamus, medial habenula, and the medial septum/diagonal band region. The proportion of total specific binding corresponding to μ 1 sites varied among the regions, ranging from 14% to 75% for [ 3 H][D-Ala 2 , D-Leu 5 ]enkephalin and 20% to 52% for [ 3 H]dihydromorphine

  3. One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.

    Science.gov (United States)

    Waise, T M Zaved; Toshinai, Koji; Naznin, Farhana; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu

    2015-09-04

    A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Distribution of angiotensin converting enzyme in sheep hypothalamus and medulla oblongata visualized by in vitro autoradiography

    International Nuclear Information System (INIS)

    Chai, S.Y.; McKinley, M.J.; Mendelsohn, F.A.

    1987-01-01

    In vitro autoradiographic mapping of angiotensin converting enzyme (ACE) in sheep brain using the specific ACE inhibitor, 125 I-351A, revealed very high densities of binding in large blood vessels and choroid plexus. In the a very high density of labelling occurred in the organum vasculosum of the lamina terminalis and median eminence and a high density in the subfornical organ and moderate density in supraoptic, suprachiasmatic, arcuate and paraventricular nuclei. All fiber tracts were unlabelled. In the medulla oblongata, a very high density of binding was detected in the area postrema and a high density in the nucleus of the solitary tract and dorsal motor nucleus of the vagus; a moderate density was found in the substantia gelatinosa of the spinal tract and the inferior olivary nucleus

  5. Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas; Balchen, T; Bruhn, T

    1999-01-01

    A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral...... artery (MCAO) in rats. In halothane anesthesia, the left middle cerebral artery was permanently occluded. Two hours after MCAO an i.v. bolus injection of 14C-deoxyglucose and 3H-leucine was given and circulated for 45 min. Two sets of brain sections were processed for quantitative autoradiography....... Neighboring brain sections exposed an X-ray film (3H-insensitive), and a 3H-sensitive for determination of rCMRglc and PS, respectively. Sections for PS determination were washed in trichloroacetic acid (TCA) prior to film exposure in order to remove 14C-deoxyglucose and unincorporated 3H-leucine. Regional...

  6. Autoradiographic localization of target cells for 1α, 25-dihydroxyvitamin D3 in bones from fetal rats

    International Nuclear Information System (INIS)

    Narbaitz, R.; Stumpf, W.E.; Sar, M.; Huang, S.; DeLuca, H.F.

    1983-01-01

    Thaw-mount autoradiographic studies after injection of 3 H-1,25-D 3 were conducted on 18- and 20-day-old rat fetuses. In maxillary bones, ribs, and tibia, nuclear concentration of radioactivity was found in osteoprogenitor cells and osteoblasts. Osteocytes and chondrocytes in epiphyseal plates were either unlabeled or weakly labeled. In competition experiments, nuclear concentration of radioactivity was blocked by the injection of a high dose of nonradioactive 1,25-D 3 prior to the administration of the labeled hormone, but not by a similar dose of nonradioactive 25-D 3 . The results are interpreted as indicating that osteoprogenitor cells and osteoblasts are target cells for the direct action of 1,25-D 3 on fetal bone. (orig.)

  7. Utilization of plastic detectors in autoradiographic studies of radioactive minerals from the Lagoa Real uranium Province, state of Bahia, Brazil

    International Nuclear Information System (INIS)

    Brandao, P.M.C.

    1984-01-01

    A short account on an autoradiographic technique using plastic detectors, it's methodology, application and results is presented. With this technique the distribution of radioactive minerals in rocks can be studied in detail. As radioactive source for this study, samples mineralized in uraninite and/or pitchblende were used. The utilized detectors were the CR-39 (a polymer plate) and films of celulose nitrate: CA-80-15 and CN-85. The mineralization is associated to mafics (amphibole, pyroxene, biotite, garnet, etc.) and to plagioclase (albite or albite-oligoclase), occurring as small inclusions and also in microfractures, cleavages and grain boundaries, mainly among plagioclase crystals which occur close to or practically touching mafic minerals. (Author) [pt

  8. Autoradiographic localization of glucocorticosteriod binding sites in rat brain after in vivo injection of [3H]RU 28362

    International Nuclear Information System (INIS)

    Sarrieau, Alain; Dussaillant, Monique; Rostene, William

    1988-01-01

    The autoradiographic distribution of glucocorticosteriod binding sites in the brain of adrenalectomized rats was studied following in vivo injection of a potent synthetic glucocorticosteriod agonist [ 3 H]RU 28362. Analysis of the autoradiograms revealed a specific and dense labelling in the pyramidal cell layer of the Ammon's horn and in the granular cell layer of the dentate gyrus of the hippocampus. In the hypothalmus, the labelling was particularly high in the paraventricular nucleus (site of CRF synthesis), the arcuate, periventricular and the supraoptic nuclei as well as in the median eminence. Autoradiograms also revealed the presence of[ 3 H]RU 28362 binding sites in several brain regions including the amygdala, the pineal gland, the entorhinal cortex, the interpeduncular, interfascicular and dorsal raphe nuclei, the central grey and the substantia nigra suggesting possible effects of glucocorticosteriods in these structures (author)

  9. Autoradiographic demonstration of unscheduled DNA synthesis in oral tissues treated with chemical carcinogens in short-term organ culture

    International Nuclear Information System (INIS)

    Ide, F.; Umemura, S.; Ishikawa, T.; Takayama, S.

    1981-01-01

    A system in which oral tissues of inbred F344 adult rats and Syrian golden hamster embryos were used in combination with autoradiography was developed for measurement of unscheduled DNA synthesis (UDS). For this, oral mucosa, submandibular gland, tooth germ and mandible in short-term organ cultures were treated with 4-nitroquinoline l-oxide or N-methyl-N-nitrosourea plus (methyl- 3 H)thymidine. Significant numbers of silver grains, indicating UDS, were detected over the nuclei of cells of all these tissues except rat salivary gland after treatment with carcinogens. This autoradiographic method is suitable for detection of UDS in oral tissues in conditions mimicking those in vivo. Results obtained in this study indicated a potential use of this system for studies on the mechanism of carcinogenesis at a cellular level comparable to in vivo carcinogenesis studies on oral tissues. (author)

  10. Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus.

    Science.gov (United States)

    Choi, Gloria B; Dong, Hong-Wei; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Swanson, Larry W; Anderson, David J

    2005-05-19

    In mammals, innate reproductive and defensive behaviors are mediated by anatomically segregated connections between the amygdala and hypothalamus. This anatomic segregation poses the problem of how the brain integrates activity in these circuits when faced with conflicting stimuli eliciting such mutually exclusive behaviors. Using genetically encoded and conventional axonal tracers, we have found that the transcription factor Lhx6 delineates the reproductive branch of this pathway. Other Lhx proteins mark neurons in amygdalar nuclei implicated in defense. We have traced parallel projections from the posterior medial amygdala, activated by reproductive or defensive olfactory stimuli, respectively, to a point of convergence in the ventromedial hypothalamus. The opposite neurotransmitter phenotypes of these convergent projections suggest a "gate control" mechanism for the inhibition of reproductive behaviors by threatening stimuli. Our data therefore identify a potential neural substrate for integrating the influences of conflicting behavioral cues and a transcription factor family that may contribute to the development of this substrate.

  11. Picomolar-affinity binding and inhibition of adenylate cyclase activity by melatonin in Syrian hamster hypothalamus

    International Nuclear Information System (INIS)

    Niles, L.P.; Hashemi, F.

    1990-01-01

    1. The effect of melatonin on forskolin-stimulated adenylate cyclase activity was measured in homogenates of Syrian hamster hypothalamus. In addition, the saturation binding characteristics of the melatonin receptor ligand, [ 125 I]iodomelatonin, was examined using an incubation temperature (30 degree C) similar to that used in enzyme assays. 2. At concentrations ranging from 10 pM to 1 nM, melatonin caused a significant decrease in stimulated adenylate cyclase activity with a maximum inhibition of approximately 22%. 3. Binding experiments utilizing [ 125 I]iodomelatonin in a range of approximately 5-80 pM indicated a single class of high-affinity sites: Kd = 55 +/- 9 pM, Bmax = 1.1 +/- 0.3 fmol/mg protein. 4. The ability of picomolar concentrations of melatonin to inhibit forskolin-stimulated adenylate cyclase activity suggests that this affect is mediated by picomolar-affinity receptor binding sites for this hormone in the hypothalamus

  12. Cholecystokinin receptors: Biochemical demonstration and autoradiographical localization in rat brain and pancreas using [3H] cholecystokinin8 as radioligand

    International Nuclear Information System (INIS)

    Van Dijk, A.; Richards, J.G.; Trzeciak, A.; Gillessen, D.; Moehler, H.

    1984-01-01

    Since cholecystokinin8 (CCK8) seems to be the physiological ligand of CCK receptors in the brain, it would be the most suitable probe for the characterization of CCK receptors in radioligand binding studies. [ 3 H]CCK8 was synthetized with a specific radioactivity sufficient for the detection of high affinity binding sites. [ 3 H]CCK8 binds saturably and reversibly to distinct sites in rat brain and pancreas with nanomolar affinity. While the C-terminal tetrapeptide of CCK is the minimal structure required for nanomolar affinity in the brain, the entire octapeptide sequence is required for binding affinity in pancreas. Desulfated CCK8 and several gastrin-I peptides, which are likewise unsulfated, show virtually no affinity to the binding sites in pancreas but high affinity in cerebral cortex. The ligand specificity of the CCK peptides corresponds to their electrophysiological potency in the brain and their stimulation of secretion in pancreas, respectively. Autoradiographically, high densities of [ 3 H]CCK8 binding sites were found in cerebral cortex and olfactory bulb, medium levels in nucleus accumbens, hippocampus, dentate gyrus, and striatum with virtually no labeling in cerebellum. This pattern is similar to the distribution of CCK-like immunoreactivity in the brain. In pancreas, equally high levels of [ 3 H]CCK8 labeling were found in the exocrine and endocrine region. [ 3 H]CCK8 binding sites differ from those identified previously with [ 125 I]Bolton-Hunter-CCK33 by their sensitivity to guanyl nucleotides in the brain, their ion dependency in the brain, and pancreas, and their different autoradiographical localization in some parts of the brain. The distribution of CCK binding sites labeled with [ 3 H]CCK8 appears to correlate better with the CCK immunoreactivity than those labeled with [ 125 I]Bolton-Hunter-CCK33. Thus, [ 3 H]CCK8 appears to be the radioligand of choice for the investigation of CCK receptors

  13. Stability Analysis for an Extended Model of the Hypothalamus-Pituitary-Thyroid Axis

    OpenAIRE

    Beata Jackowska-Zduniak

    2016-01-01

    We formulate and analyze a mathematical model describing dynamics of the hypothalamus-pituitary-thyroid homoeostatic mechanism in endocrine system. We introduce to this system two types of couplings and delay. In our model, feedback controls the secretion of thyroid hormones and delay reflects time lags required for transportation of the hormones. The influence of delayed feedback on the stability behaviour of the system is discussed. Analytical results are illustrated by...

  14. Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion

    OpenAIRE

    Qualls-Creekmore, Emily; Yu, Sangho; Francois, Marie; Hoang, John; Huesing, Clara; Bruce-Keller, Annadora; Burk, David; Berthoud, Hans-Rudolf; Morrison, Christopher D.; Münzberg, Heike

    2017-01-01

    The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHAGABA), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHAGABA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHAGABA neurons that coexpress the neuropeptide galanin (LHAGal). These LHAGal n...

  15. Progesterone metabolism by the hypothalamus, pituitary, and uterus of the rat during pregnancy

    International Nuclear Information System (INIS)

    Marrone, B.L.; Karavolas, H.J.

    1981-01-01

    Metabolites of [ 3 H]progesterone were quantitated from incubations of hypothalamus, pituitary, and uterus of rats during different stages of pregnancy. The hypothalamus, anterior pituitary, and a section of uterus from five rats on Days 1, 8, 15, and 21 of pregnancy were incubated individually with [3H]progesterone and analyzed for metabolite formation by reverse isotopic dilution analysis. The radioactive metabolites present were 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one, 20 alpha-hydroxy-4-pregnen-3-one, 20 alpha-hydroxy-5 alpha-pregnan-3-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol. The major metabolite formed by the hypothalamus and pituitary was 5 alpha-DHP. In the pituitary samples, formation of 5 alpha-DHP was decreased on Days 15 and 21 of pregnancy compared to Day 1, and formation of 20 alpha-hydroxy-5 alpha-pregnan-3-one was decreased on Day 21 compared to Day 1. In the uterine samples, 3 alpha-hydroxy-5 alpha-pregnan-20-one was the major metabolite formed at all stages of pregnancy. The formation of all metabolic products of progesterone by the uterus was increased on Day 21 compared to Days 1, 8, and 15 of pregnancy. No changes in the formation of progesterone metabolites were observed in the hypothalamic samples during pregnancy. It is concluded that there are different profiles in the in vitro metabolism of [3H]progesterone by the hypothalamus, pituitary, and uterus of the rat during the course of pregnancy

  16. A route for direct retinal input to the preoptic hypothalamus: dendritic projections into the optic chiasm.

    Science.gov (United States)

    Silver, J; Brand, S

    1979-07-01

    With the use of Golgi, horseradish peroxidase, and electron microscopic techniques, neurons within a broad region of the preoptic hypothalamus of the mouse were shown to have dendrites that projected well into the depths of the optic chiasm. Further experimental and ultrastructural investigation demonstrated synapses between these dendrites and retinal axonal boutons within the chiasm. All synapses located in the chiasm were classified as Gray's type I. The possible function of these dendritic projections is discussed.

  17. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    OpenAIRE

    Whirledge, Shannon; Cidlowski, John A.

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that oth...

  18. Hypothalamus-Related Resting Brain Network Underlying Short-Term Acupuncture Treatment in Primary Hypertension

    Directory of Open Access Journals (Sweden)

    Hongyan Chen

    2013-01-01

    Full Text Available The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP and heart rate (HR decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005 decreased and vitality (P = 0.036 increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem.

  19. Large central lesions compressing the hypothalamus and brainstem. Operative approaches and combination treatment with radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Hiroshi K.; Negishi, Masatoshi; Kohga, Hideaki; Hirato, Masafumi; Ohye, Chihiro [Gunma Univ., Maebashi (Japan). School of Medicine; Shibazaki, Tohru

    1998-09-01

    A major aim of minimally invasive neurosurgery is to preserve function in the brain and cranial nerves. Based on previous results of radiosurgery for central lesions (19 craniopharyngiomas, 46 pituitary adenomas, 9 meningeal tumors), combined micro- and/or radiosurgery was applied for large lesions compressing the hypothalamus and/or brainstem. A basal interhemispheric approach via superomedial orbitotomy or a transcallosal-transforaminal approach was used for these large tumors. Tumors left behind in the hypothalamus or cavernous sinus were treated with radiosurgery using a gamma unit. Preoperative hypothalamo-pituitary functions were preserved in most of these patients. Radiosurgical results were evaluated in patients followed for more than 2 years after treatment. All 9 craniopharyngiomas decreased in size after radiosurgery, although a second treatment was required in 4 patients. All 20 pituitary adenomas were stable or decreased in size and 5 of 7 functioning adenomas showed normalized values of hormones in the serum. All 3 meningeal tumors were stable or decreased in size after treatment. No cavernous sinus symptoms developed after radiosurgery. We conclude that combined micro- and radio-neurosurgery is an effective and less invasive treatment for large central lesions compressing the hypothalamus and brainstem. (author)

  20. Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula.

    Directory of Open Access Journals (Sweden)

    Gabriel-Nicolás eSantos-Durán

    2015-04-01

    Full Text Available The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp and ScTbr1 expression profiles and on the identification α-acetylated-tubulin-immunoreactive (ir, TH-ir, 5-HT-ir and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates.

  1. Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula.

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    Santos-Durán, Gabriel N; Menuet, Arnaud; Lagadec, Ronan; Mayeur, Hélène; Ferreiro-Galve, Susana; Mazan, Sylvie; Rodríguez-Moldes, Isabel; Candal, Eva

    2015-01-01

    The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp, and ScTbr1 expression profiles and on the identification α-acetylated-tubulin-immunoreactive (ir), TH-ir, 5-HT-ir, and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates.

  2. Morphometry of the pituitary gland and hypothalamus in long-term survivors of childhood trauma.

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    Porto, L; Margerkurth, J; Althaus, J; You, S-J; Zanella, F E; Kieslich, M

    2011-11-01

    Chronic pituitary dysfunction is increasingly recognized as a sequela of traumatic brain injury (TBI). Our aim was to rule out any late morphometric changes of the pituitary gland and hypothalamus in survivors of TBI during childhood requiring intensive care. We assessed morphometric abnormalities of the sella region and hypothalamus in patients who sustained TBI during childhood. The patients showed no clinical hormonal dysfunction at the acute phase and pituitary hormone levels at the time of our study were within normal limits. From the 18 enrolled patients in the magnetic resonance study, five were removed due to morphological changes or anatomical variations. We studied the MRI of 13 male survivors (mean age 27 years, mean time after trauma 20 years) and compared them to 13 male control subjects who were matched in terms of age (mean age, 26 years), education and ethnicity. Analyses of the pituitary gland and sella on a midsagittal T2- and T1-weighted image were performed. We used voxel-based morphometry (VBM), an unbiased MRI morphometric method to investigate hypothalamic region in this group of patients. There was only a trend towards a reduced pituitary gland width in the patient group compared to controls. However, no significant morphological and morphometric abnormality was seen and VBM showed no hypothalamic grey matter loss. In the absence of hormonal dysfunction, no persisting morphometric changes of the pituitary gland and hypothalamus were seen in survivors of childhood TBI requiring intensive care.

  3. Active coping with stress suppresses glucose metabolism in the rat hypothalamus.

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    Ono, Yumie; Lin, Hsiao-Chun; Tzen, Kai-Yuan; Chen, Hui-Hsing; Yang, Pai-Feng; Lai, Wen-Sung; Chen, Jyh-Horng; Onozuka, Minoru; Yen, Chen-Tung

    2012-03-01

    We used 18F-fluorodeoxyglucose small-animal positron-emission tomography to determine whether different styles of coping with stress are associated with different patterns of neuronal activity in the hypothalamus. Adult rats were subjected to immobilization (IMO)-stress or to a non-immobilized condition for 30 min, in random order on separate days, each of which was followed by brain-scanning. Some rats in the immobilized condition were allowed to actively cope with the stress by chewing a wooden stick during IMO, while the other immobilized rats were given nothing to chew on. Voxel-based statistical analysis of the brain imaging data shows that chewing counteracted the stress-induced increased glucose uptake in the hypothalamus to the level of the non-immobilized condition. Region-of-interest analysis of the glucose uptake values further showed that chewing significantly suppressed stress-induced increased glucose uptake in the paraventricular hypothalamic nucleus and the anterior hypothalamic area but not in the lateral hypothalamus. Together with the finding that the mean plasma corticosterone concentration at the termination of the IMO was also significantly suppressed when rats had an opportunity to chew a wooden stick, our results showed that active coping by chewing inhibited the activation of the hypothalamic-pituitary-adrenal axis to reduce the endocrine stress response.

  4. Large central lesions compressing the hypothalamus and brainstem. Operative approaches and combination treatment with radiosurgery

    International Nuclear Information System (INIS)

    Inoue, Hiroshi K.; Negishi, Masatoshi; Kohga, Hideaki; Hirato, Masafumi; Ohye, Chihiro; Shibazaki, Tohru

    1998-01-01

    A major aim of minimally invasive neurosurgery is to preserve function in the brain and cranial nerves. Based on previous results of radiosurgery for central lesions (19 craniopharyngiomas, 46 pituitary adenomas, 9 meningeal tumors), combined micro- and/or radiosurgery was applied for large lesions compressing the hypothalamus and/or brainstem. A basal interhemispheric approach via superomedial orbitotomy or a transcallosal-transforaminal approach was used for these large tumors. Tumors left behind in the hypothalamus or cavernous sinus were treated with radiosurgery using a gamma unit. Preoperative hypothalamo-pituitary functions were preserved in most of these patients. Radiosurgical results were evaluated in patients followed for more than 2 years after treatment. All 9 craniopharyngiomas decreased in size after radiosurgery, although a second treatment was required in 4 patients. All 20 pituitary adenomas were stable or decreased in size and 5 of 7 functioning adenomas showed normalized values of hormones in the serum. All 3 meningeal tumors were stable or decreased in size after treatment. No cavernous sinus symptoms developed after radiosurgery. We conclude that combined micro- and radio-neurosurgery is an effective and less invasive treatment for large central lesions compressing the hypothalamus and brainstem. (author)

  5. Effects of heavy-ion exposure to rat's hypothalamus on the copulatory behavior

    International Nuclear Information System (INIS)

    Saito, Masayoshi; Kawata, Tetsuya; Liu, C.; Kan'o, Momoe; Ito, Hisao; Takai, Nobuhiko; Ando, Koichi

    2005-01-01

    The effect of heavy-ion irradiation to brain on sexual behavior is not yet known. The present study was designed to determine whether irradiation (carbon particles 290 MeV/nucleon, Mono peak 15∼120 Gy, irradiation field 5-millimeter cube in hypothalamus) to rat's hypothalamus modifies the copulatory behavior of male rats. For the first year, we planned to estimate the short-term effects of carbon-irradiation on the copulatory behavior using a relatively high doses, and observation of sexual behavior was conducted for 30 min after 1, 2 or 3 months following irradiation. Results obtained in the first year are as follows. At dosages of 15 Gy, 30 Gy, 45 Gy and 60 Gy these were no changes in copulatory behavior after one month following irradiation; however, the intromission and ejaculation was found to decrease after 3-month follow-up in rats exposed to 60 Gy. At higher doses such as 90 Gy, 120 Gy, the number of mounting, intromission (120 Gy alone) and ejaculation (90 Gy, 120 Gy) were decreased. It may be possible to describe that carbon irradiation to hypothalamus does not inhibit the activity of copulatory behavior after short-term. Further experiments after long-term follow-up after irradiation are necessary to determine the chronic effects of heavy ions on the copulatory behavior. (author)

  6. [Biogenic amines in the epiphysis and hypothalamus under normal conditions and following ovariectomy].

    Science.gov (United States)

    Grishchenko, V I; Koliada, L D; Demidenko, D I

    1977-01-01

    Melatonin content in the epiphysis, serotonin, noradrenaline, dopamine-in the hypothalamus, gonadotropins--in the hypophysis of rats was studied under normal conditions and following ovariectomy; regularly of the estral cycle phases was studied as well. Two series of experiments were conducted on 120 rats with regular estral cycles. The animals were divided into groups according to the estral cycle phase. Melatonin concentration in the epiphysis, serotonin, noradrenaline, dopamine--in the hypothalamus was subject to variations coinciding with the estral cycle phases. Serotonin, noradrenaline, and dopamine content decreased in the hypophysis of ovariectomized rats in comparison with control; melatonin content rose in the epiphysis. There was no complete extinction of the estral cycle in the course of investigation (20 days). The action of castration on the sexual cycle depended on the phase at which the rats were subjected to ovariectomy. A reverse relationship existed between the melatonin content in the epiphysis and serotonin content in the hypothalamus, this serving as one of the important factors in the regulation of the sexual function.

  7. Vasoactive intestinal peptide binding sites and fibers in the brain of the pigeon Columba livia: An autoradiographic and immunohistochemical study

    International Nuclear Information System (INIS)

    Hof, P.R.; Dietl, M.M.; Charnay, Y.; Martin, J.L.; Bouras, C.; Palacios, J.M.; Magistretti, P.J.

    1991-01-01

    The distribution of vasoactive intestinal peptide (VIP) binding sites in the pigeon brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of VIP, which maintains the biological activity of the native peptide, was used throughout this study. The highest densities of binding sites were observed in the hyperstriatum dorsale, archistriatum, auditory field L of neostriatum, area corticoidea dorsolateralis and temporo-parieto-occipitalis, area parahippocampalis, tectum opticum, nucleus dorsomedialis anterior thalami, and in the periventricular area of the hypothalamus. Lower densities of specific binding occurred in the neostriatum, hyperstriatum ventrale and nucleus septi lateralis, dorsolateral area of the thalamus, and lateral and posteromedial hypothalamus. Very low to background levels of VIP binding were detected in the ectostriatum, paleostriatum primitivum, paleostriatum augmentatum, lobus parolfactorius, nucleus accumbens, most of the brainstem, and the cerebellum. The distribution of VIP-containing fibers and terminals was examined by indirect immunofluorescence using a polyclonal antibody against porcine VIP. Fibers and terminals were observed in the area corticoidea dorsolateralis, area parahippocampalis, hippocampus, hyperstriatum accessorium, hyperstriatum dorsale, archistriatum, tuberculum olfactorium, nuclei dorsolateralis and dorsomedialis of the thalamus, and throughout the hypothalamus and the median eminence. Long projecting fibers were visualized in the tractus septohippocampalis. In the brainstem VIP immunoreactive fibers and terminals were observed mainly in the substantia grisea centralis, fasciculus longitudinalis medialis, lemniscus lateralis, and in the area surrounding the nuclei of the 7th, 9th, and 10th cranial nerves

  8. Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

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    Chen, Z L; Huang, R Q

    2014-06-20

    Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

  9. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    International Nuclear Information System (INIS)

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

    2011-01-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

  10. Dynamic of bioelectric activity back hypothalamus changes in conditions of pyroxan application on the background of stress-reaction developmen

    Directory of Open Access Journals (Sweden)

    T. G. Chaus

    2005-04-01

    Full Text Available The dynamic of changes of capacity of electroencephalogram’s rhythms back hypothalamus at animals of control group and group in stress conditions in parallel with rats who on a background of stress development accepted pyroxan is analyzed. The submitted results have shown influence of a pharmacological preparation pyroxan on bioelectric activity of back hypothalamus in stress conditions that restoration of electric activity under action of this preparation was more shown at 3 weeks of its application.

  11. [The catecholamine content of the hypothalamus during the modelling of the ulcer process in the gastroduodenal area].

    Science.gov (United States)

    Iemel'ianenko, I V; Sultanova, I D; Voronych, N M

    1995-01-01

    The content of catecholamines in rat hypothalamus in experimental ulcer process in gastroduodenal region has been studied in experiments on rats. It was determined that under these conditions the content of hypothalamus adrenalin increases and the content of noradrenalin decreases. The level of dofamin and DOFA in this brain structure changes in phases. The mentioned shifts depended on the duration and character of the pathological process in the gastroduodenal region.

  12. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  13. Effect of prolonged gamma irradiation (6.7 Gy) on monoamine oxidase activity in ewe hypothalamus in anestral period

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.

    1988-01-01

    Changes were studied of monoamine oxidase (MAO) activity in the hypothalamus and hypophysis of ewes in the anestral period following whole-body 60 Co irradiation for 7 days with a dose of 6.7 Gy. The gamma radiation exposure rate was 0.039 Gy/h. The activity of MAO was determined using the radiochemical method. 14 C-tryptamine was used as the substrate. The highest activity was determined in the rostral hypothalamus (1100 pmol.mg -1 .min -1 ). MAO activity was at its lowest in the caudal region of the hypothalamus (550 pmol). The results show that whole-body exposure to gamma radiation with a total dose of 6.7 Gy makes a statistically significant increase (P<0.001) in MAO activity in the caudal hypothalamus of ewes while remaining at the level of the control group or increasing insignificantly in the rostral and medial hypothalamus. A significant decrease (P<0.05) was recorded in the hypophysis. It may be assumed that the increased degradation of catecholamines caused by MAO is one of the mechanisms responsible for the decreased concentration of catecholamines in the hypothalamus of ewes after irradiation. (author). 1 fig., 22 refs

  14. Genome-wide analysis of DHEA- and DHT-induced gene expression in mouse hypothalamus and hippocampus.

    Science.gov (United States)

    Mo, Qianxing; Lu, Shifang; Garippa, Carrie; Brownstein, Michael J; Simon, Neal G

    2009-04-01

    Dehydroepiandrosterone (DHEA) is the most abundant steroid in humans and a multi-functional neuroactive steroid that has been implicated in a variety of biological effects in both the periphery and central nervous system. Mechanistic studies of DHEA in the periphery have emphasized its role as a prohormone and those in the brain have focused on effects exerted at cell surface receptors. Recent results demonstrated that DHEA is intrinsically androgenic. It competes with DHT for binding to androgen receptor (AR), induces AR-regulated reporter gene expression in vitro, and exogenous DHEA administration regulates gene expression in peripheral androgen-dependent tissues and LnCAP prostate cancer cells, indicating genomic effects and adding a level of complexity to functional models. The absence of information about the effect of DHEA on gene expression in the CNS is a significant gap in light of continuing clinical interest in the compound as a hormone replacement therapy in older individuals, patients with adrenal insufficiency, and as a treatment that improves sense of well-being, increases libido, relieves depressive symptoms, and serves as a neuroprotective agent. In the present study, ovariectomized CF-1 female mice, an established model for assessing CNS effects of androgens, were treated with DHEA (1mg/day), dihydrotestosterone (DHT, a potent androgen used as a positive control; 0.1mg/day) or vehicle (negative control) for 7 days. The effects of DHEA on gene expression were assessed in two regions of the CNS that are enriched in AR, hypothalamus and hippocampus, using DNA microarray, real-time RT-PCR, and immunohistochemistry. RIA of serum samples assessed treatment effects on circulating levels of major steroids. In hypothalamus, DHEA and DHT significantly up-regulated the gene expression of hypocretin (Hcrt; also called orexin), pro-melanin-concentrating hormone (Pmch), and protein kinase C delta (Prkcd), and down-regulated the expression of deleted in bladder

  15. Autoradiographic detection of [125I]-secondary antiserum: a sensitive light and electron microscopic labeling method compatible with peroxidase immunocytochemistry for dual localization of neuronal antigens

    International Nuclear Information System (INIS)

    Pickel, V.M.; Chan, J.; Milner, T.A.

    1986-01-01

    We examined whether autoradiographic localization of [ 125 I]-antirabbit immunoglobulin (IgG) was suitable for light and electron microscopic detection of a rabbit antiserum to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), and whether autoradiographic and peroxidase labeling could be combined for simultaneous immunocytochemical identification of TH and neuropeptides in brain. Adult rat brains were fixed by aortic arch perfusion with acrolein and paraformaldehyde. Vibratome sections of the fixed tissues were incubated with various dilutions of TH antiserum followed by [ 125 I]-secondary IgG. These sections were then directly processed for autoradiography or were incubated with rabbit antiserum to substance P (SP) or methionine [Met5]-enkephalin (ME). These latter sections were then processed by the peroxidase-antiperoxidase (PAP) or conjugated peroxidase methods followed by autoradiography. Exposure periods of 12-20 days for light microscopy or 90 days for electron microscopy yielded substantial accumulations of silver grains even at the highest (1:30,000) dilution of TH antiserum. At this dilution, immunoreactivity for TH was virtually nondetectable by PAP and conjugated peroxidase methods. The differential sensitivities of the autoradiographic versus peroxidase methods provided a means for separable identification of rabbit antiserum to TH and to SP or ME. Ultrastructural analysis of the catecholaminergic neurons in the medial nuclei of the solitary tract (NTS) showed selective cytoplasmic localization of silver grains for [ 125 I]-labeling of TH in perikarya, dendrites, and terminals. Within single thin sections prepared for dual labeling, the peroxidase marker for SP and for ME was differentially localized with respect to autoradiographic labeling of TH

  16. Immunoassay of poliovirus antigens by single-radial-diffusion: development and characteristics of a sensitive autoradiographic zone size enhancement (ZE) technique

    International Nuclear Information System (INIS)

    Schild, G.C.; Wood, J.M.; Minor, P.D.; Dandawate, C.N.; Magrath, D.I.

    1980-01-01

    The reactions of polioviruses in single-radial-immunodiffusion (SRD) tests were investigated with a view to developing accurate and sensitive antigen assay systems. In direct SRD tests, the reactions were type-specific for polioviruses of types 1, 2 and 3 but the tests were of low sensitivity, being applicable only to the assay of virus concentrates. A novel autoradiographic zone size enhancement (ZE) test was developed which increased the sensitivity of the SRD assay 40-to 100-fold. The ZE test was dependent upon the ability of unlabelled poliovirus to co-migrate with the radioactive marker virus and so enhance the zone size detected autoradiographically. The areas of the autoradiographic zones were directly proportional to the concentration of unlabelled antigen. The ZE test was capable of detecting poliovirus D antigens in amounts corresponding to 10sup(3.3) to 10sup(4.3) TCID 50 of infectious virus. Studies with poliovirus type 3 strains indicated that the ZE test was narrowly strain-specific for the D-antigen of poliovirus type 3 strains when homologous type 3 D-antigen was used as radioactive marker, but broadly cross-reactive for the D-antigen of type 3 viruses when heterologous poliovirus type 3 D-antigen was used as marker. (author)

  17. Autoradiographic detection of mutation to exotoxin-A resistance in mouse fibroblasts treated with ethyl methanesulfonate, X-rays and ultraviolet light

    International Nuclear Information System (INIS)

    Tiah, M.; Ronen, A.

    1989-01-01

    P. aeruginosa exotoxin-A (PE) blocks protein synthesis in mammalian cells by inactivating elongation factor 2 (EF-2). Toxin-resistant mutant cells can be detected autoradioraphically, in cultures grown on microscope coverslips in the presence of PE, and exposed to [ 3 H]leucine. The frequency of PE-resistant cells detected by the autoradiographic assay in non-mutagenized cells of the established mouse cell line LTKA is 9.7 j 0.6 x 10 -5 . Upon treatment with ethyl methanesulfonate (EMS), X-rays of ultraviolet (UV) light it increases in a dose-dependent fashion. The mutational nature of the resistance detected by the assay is indicated by its clonal inheritance, and by the dose-dependent increase in the frequency of resistant cells after utagenesis. On the basis of the high frequency of PE-resistant cells detected by the autoradiographic assay, and their cross-resistance to diphteria toxin (DT), the authors suggest that the PE-resistant mutants detected by the autoradiographic assay are of class II, i.e., they are altered in the structural gene for EF-2. (author). 27 refs.; 5 figs.; 3 tabs

  18. Octylphenol (OP) alters the expression of members of the amyloid protein family in the hypothalamus of the snapping turtle, Chelydra serpentina serpentina.

    Science.gov (United States)

    Trudeau, Vance L; Chiu, Suzanne; Kennedy, Sean W; Brooks, Ronald J

    2002-03-01

    The gonadal estrogen estradiol-17beta (E(2)) is important for developing and regulating hypothalamic function and many aspects of reproduction in vertebrates. Pollutants such as octylphenol (OP) that mimic the actions of estrogens are therefore candidate endocrine-disrupting chemicals. We used a differential display strategy (RNA-arbitrarily primed polymerase chain reaction) to isolate partial cDNA sequences of neurotransmitter, developmental, and disease-related genes that may be regulated by OP or E(2) in the snapping turtle Chelydra serpentina serpentina hypothalamus. Hatchling and year-old male snapping turtles were exposed to a 10 ng/mL nominal concentration of waterborne OP or E(2) for 17 days. One transcript [421 base pairs (bp)] regulated by OP and E(2) was 93% identical to human APLP-2. APLP-2 and the amyloid precursor protein (APP) regulate neuronal differentiation and are also implicated in the genesis of Alzheimer disease in humans. Northern blot analysis determined that the turtle hypothalamus contains a single APLP-2 transcript of 3.75 kb in length. Exposure to OP upregulated hypothalamic APLP-2 mRNA levels 2-fold (p < 0.05) in month-old and yearling turtles. E(2) did not affect APLP-2 mRNA levels in hatchlings but stimulated a 2-fold increase (p < 0.05) in APLP-2 mRNA levels in yearling males. The protein beta-amyloid, a selectively processed peptide derived from APP, is also involved in neuronal differentiation, and accumulation of this neurotoxic peptide causes neuronal degeneration in the brains of patients with Alzheimer disease. Therefore, we also sought to determine the effects of estrogens on the expression of beta-amyloid. Using homology cloning based on known sequences, we isolated a cDNA fragment (474 bp) from turtle brain with 88% identity to human APP. Northern blot analysis determined that a single 3.5-kb transcript was expressed in the turtle hypothalamus. Waterborne OP also increased the expression of hypothalamic APP after 35 days of

  19. Autoradiographic methods for studying marked volatile substances (1961); Methode.d'etude autoradiographique de substances marquees volatiles (1961)

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Y; Wepierre, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1961-07-01

    The autoradiographic methods for animals used up to the present do not make it possible to localise exactly the distribution of marked volatile molecules. The Ullberg method (1954) which we have modified (Cohen, Delassue, 1959) involves cold desiccant. The method due to Pellerin (1957) avoids this desiccant but the histological comparison of the autoradiography with the biological document itself is difficult, if not impossible. Nevertheless, we have adopted certain points in the two methods and propose the following technique for the autoradiographic study of marked volatile molecules: 1- The surface of the frozen sample to be studied is prepared using a freezing microtome. 2- The last section, which is 20 {mu} thick and whose histological elements are parallel to those of the block, is dried by cooling and is used as the biological reference document for the autoradiography obtained, as is indicated in 3; 3- The radiography films are applied to the frozen block at -30 deg. C. The autoradiographs correspond to the radioactivity of the volatile molecule and of its non-volatile degradation products. 4- The radiographic film is also applied to the 20 {mu} section previously dried at -20 deg. C. This autoradiography corresponds to the radioactivity of the non-volatile degradation products of the molecule. 5- We confirmed the absence of diffusion of the volatile molecule and of pseudo-radiographic effects (photochemical and others). This method, which has enabled us to study the distribution of a carbide, para-cymene (C{sup 14}) 7, macroscopically in the case of a whole mouse and microscopically on the skin of a dog, can find general applications. (authors) [French] Les methodes d'autoradiographies sur l'animal, proposees jusqu'a present, ne permettent pas de localiser de facon precise la distribution de molecules marquees volatiles. En effet, la methode de Ullberg (1954) que nous avons modifiee (Cohen, Delassue, 1959) necessite la dessiccation par le froid. La methode

  20. Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin-releasing hormone neurons

    NARCIS (Netherlands)

    Goncharuk, Valeri D.; van Heerikhuize, Joop; Swaab, Dick F.; Buijs, Ruud M.

    2002-01-01

    By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH)-producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control

  1. The stress system in depression and neurodegeneration: focus on the human hypothalamus.

    Science.gov (United States)

    Bao, A-M; Meynen, G; Swaab, D F

    2008-03-01

    The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the pituitary, which subsequently causes cortisol release from the adrenal cortex. The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects. CRH neurons project not only to the median eminence but also into brain areas where they, e.g., regulate the adrenal innervation of the autonomic system and affect mood. The hypothalamo-neurohypophysial system is also involved in stress response. It releases AVP from the PVN and the supraoptic nucleus (SON) and oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the rhythmic changes of the stress system. Both centrally released CRH and increased levels of cortisol contribute to the signs and symptoms of depression. Symptoms of depression can be induced in experimental animals by intracerebroventricular injection of CRH. Depression is also a frequent side effect of glucocorticoid treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the hypothalamic PVN and SON are also activated in depression, which contributes to the increased release of ACTH from the pituitary. Increased levels of circulating AVP are also associated with the risk for suicide. The prevalence, incidence and morbidity risk for depression are higher in females than in males and fluctuations in sex hormone levels are considered to be involved in the etiology. About 40% of the activated CRH neurons in mood disorders co-express nuclear estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have been found in the CRH gene promoter region, and estrogens stimulate CRH production. An androgen-responsive element in the CRH gene promoter region initiates a suppressing effect on CRH expression. The decreased activity of the SCN is the basis for the disturbances of circadian and circannual fluctuations in mood, sleep and hormonal rhythms found in depression. Neuronal loss was also reported in the hippocampus of stressed or corticosteroid-treated rodents and primates. Because of the inhibitory control of the hippocampus on the HPA-axis, damage to this structure was expected to disinhibit the HPA-axis, and to cause a positive feedforward cascade of increasing glucocorticoid levels over time. This 'glucocorticoid cascade hypothesis' of stress and hippocampal damage was proposed to be causally involved in age-related accumulation of hippocampal damage in disorders like Alzheimer's disease and depression. However, in postmortem studies we could not find the presumed hippocampal damage of steroid overexposure in either depressed patients or in patients treated with synthetic steroids.

  2. Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland

    NARCIS (Netherlands)

    Fliers, Eric; Unmehopa, Unga A.; Alkemade, Anneke

    2006-01-01

    A major change in thyroid setpoint regulation occurs in various clinical conditions such as critical illness and psychiatric disorders. As a first step towards identifying determinants of these setpoint changes, we have studied the distribution and expression of thyroid hormone receptor (TR)

  3. The stress system in depression and neurodegeneration: Focus on the human hypothalamus

    NARCIS (Netherlands)

    Bao, A.-M.; Meynen, G.; Swaab, D.F.

    2008-01-01

    The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH)

  4. Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.

    Science.gov (United States)

    Akubuiro, A; Bridget Zimmerman, M; Boles Ponto, L L; Walsh, S A; Sunderland, J; McCormick, L; Singh, M

    2013-04-01

    ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region. Genes, Brain and Behavior © 2013 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  5. Effect of monochromatic light on circadian rhythmic expression of clock genes in the hypothalamus of chick.

    Science.gov (United States)

    Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

    2017-08-01

    To clarify the effect of monochromatic light on circadian clock gene expression in chick hypothalamus, a total 240 newly hatched chickens were reared under blue light (BL), green light (GL), red light (RL) and white light (WL), respectively. On the post-hatched day 14, 24-h profiles of seven core clock genes (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2 and cPer3) were measured at six time points (CT 0, CT 4, CT 8, CT 12, CT 16, CT 20, circadian time). We found all these clock genes expressed with a significant rhythmicity in different light wavelength groups. Meanwhile, cClock and cBmal1 showed a high level under GL, and followed a corresponding high expression of cCry1. However, RL decreased the expression levels of these genes. Be consistent with the mRNA level, CLOCK and BMAL1 proteins also showed a high level under GL. The CLOCK-like immunoreactive neurons were observed not only in the SCN, but also in the non-SCN brain region such as the nucleus anterior medialis hypothalami, the periventricularis nucleus, the paraventricular nucleus and the median eminence. All these results are consistent with the auto-regulatory circadian feedback loop, and indicate that GL may play an important role on the circadian time generation and development in the chick hypothalamus. Our results also suggest that the circadian clock in the chick hypothalamus such as non-SCN brain region were involved in the regulation of photo information. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Melatonin modulates monochromatic light-induced melatonin receptor expression in the hypothalamus of chicks.

    Science.gov (United States)

    Zhang, Liwei; Chen, Funing; Cao, Jing; Dong, Yulan; Wang, Zixu; Chen, Yaoxing

    2017-09-01

    To study the mechanism of the effect of monochromatic light on physiological function in chicken, a total of 192 newly hatched chicks were randomly divided into intact, sham-operated and pinealectomy groups then exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) using a light-emitting diode (LED) system for two weeks. At P14, the hypothalami were immediately collected for immunohistochemical staining of melatonin receptor subtypes (Mel1a and Mel1b) and detection of Mel1a and Mel1b expressions using RT-PCR and western blot. Immunohistochemical staining of the hypothalamus showed that the Mel1a-ir cells were distributed in the preoptic area (POA), nucleus preopticus periventricularis (POP) and suprachiasmatic nuclei (SCN), and the Mel1b-ir cells were presented in the POA and SCN. Analysis of RT-PCR and western blot showed that the mRNA and protein levels of Mel1a and Mel1b in the hypothalamus of chick exposed to GL were increased by 10.7-29.3%, 9.18-35.9% and 8.97-27.3% compared to those in the chicks exposed to WL (P=0.029-0.002), RL (P=0.027-0.001) and BL (P=0.038-0.007) in the intact group, respectively. After pinealectomy, however, these parameters decreased and there were no significant differences among the WL, RL, GL and BL groups. These findings suggested that melatonin plays a critical role in GL illumination-enhanced Mel1a and Mel1b expressions in the hypothalamus of chicks. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. The role of hypothalamus tuberomammillary nucleus on the regulation of respiratory movement of rats with asthma

    Directory of Open Access Journals (Sweden)

    Chen CHEN

    2016-01-01

    Full Text Available Objective  To explore the role of central histaminergic neurons in the tuberomammillary nucleus (TMN of posterior hypothalamus on asthma. Methods  Seventy-two healthy male SD rats were served as study objects. Sixty-four rats were sensitized with ovalbumin (OA solution intraperitoneally and challenged with OA aerosol inhalation to prepare asthma model. Asthma attack was evoked in asthmatic rats by OA solution injected intravenously, the electrical activities of TMN in posterior hypothalamus were recorded with biological signal collecting system and the power spectra were analyzed. TMN was lesioned or stimulated electrically by central stereo positioning technology. Histamine H3 receptor agonist R-(α-methylhistamine (RMHA or antagonist thioperamide (THIO was microinjected into TMN by central nuclear group microinjection technology, and the pulmonary function indexes were detected including diaphragm electromyography (EMGdi frequency, EMGdi integral, minute ventilation volume (MVV, expiratory time/inspiratory time (TE/TI, airway resistance (Raw and dynamic pulmonary compliance (Cdyn. Results  Compared with control group, the percentage of α, β1 and β2 wave in the electrical activities of TMN of asthmatic rats increased significantly, while the percentage of δ and θ wave decreased and the total discharge power increased. Compared with the corresponding control group, electric lesion of TMN or TMN microinjected with histamine H3 receptor antagonist increased EMGdi frequency, TE/TI, Raw, and decreased EMGdi integral, MVV and Cdyn. Compared with the corresponding control group, electric stimulation of TMN or TMN microinjected with histamine H3 receptor agonist decreased EMGdi frequency, TE/TI, Raw, and increased EMGdi integral, MVV and Cdyn. Conclusion  Central histaminergic neurons in tuberomammillary nucleus of posterior hypothalamus are activated in asthmatic rats. DOI: 10.11855/j.issn.0577-7402.2015.12.09

  8. Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

    Science.gov (United States)

    Villa, R F; Ferrari, F; Gorini, A

    2012-12-27

    Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

  9. Neonatal maternal separation up-regulates protein signalling for cell survival in rat hypothalamus.

    Science.gov (United States)

    Irles, Claudine; Nava-Kopp, Alicia T; Morán, Julio; Zhang, Limei

    2014-05-01

    We have previously reported that in response to early life stress, such as maternal hyperthyroidism and maternal separation (MS), the rat hypothalamic vasopressinergic system becomes up-regulated, showing enlarged nuclear volume and cell number, with stress hyperresponsivity and high anxiety during adulthood. The detailed signaling pathways involving cell death/survival, modified by adverse experiences in this developmental window remains unknown. Here, we report the effects of MS on cellular density and time-dependent fluctuations of the expression of pro- and anti-apoptotic factors during the development of the hypothalamus. Neonatal male rats were exposed to 3 h-daily MS from postnatal days 2 to 15 (PND 2-15). Cellular density was assessed in the hypothalamus at PND 21 using methylene blue staining, and neuronal nuclear specific protein and glial fibrillary acidic protein immunostaining at PND 36. Expression of factors related to apoptosis and cell survival in the hypothalamus was examined at PND 1, 3, 6, 9, 12, 15, 20 and 43 by Western blot. Rats subjected to MS exhibited greater cell-density and increased neuronal density in all hypothalamic regions assessed. The time course of protein expression in the postnatal brain showed: (1) decreased expression of active caspase 3; (2) increased Bcl-2/Bax ratio; (3) increased activation of ERK1/2, Akt and inactivation of Bad; PND 15 and PND 20 were the most prominent time-points. These data indicate that MS can induce hypothalamic structural reorganization by promoting survival, suppressing cell death pathways, increasing cellular density which may alter the contribution of these modified regions to homeostasis.

  10. State-dependent cellular activity patterns of the cat paraventricular hypothalamus measured by reflectance imaging

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, D M; Poe, G R

    1996-01-01

    Activity within the cat paraventricular hypothalamus (PVH) during sleep and waking states was measured by quantifying intrinsic tissue reflectivity. A fiber optic probe consisting of a 1.0 mm coherent image conduit, surrounded by plastic fibers which conducted 660 nm source light, was attached...... to a charge-coupled device camera, and positioned over the PVH in five cats. Electrodes for assessing state variables, including electroencephalographic activity, eye movement, and somatic muscle tone were also placed. After surgical recovery, reflected light intensity was measured continuously at 2.5 Hz...

  11. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  12. Effect of β-endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-01-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus

  13. Turnover of Biogenic Amines in the Hypothalamus of Rats during Pyrogen Fever

    Science.gov (United States)

    Penn, P. E.; Williams, B. A.

    1979-01-01

    Many pharmacological studies have implicated the biogenic amines in the hypothalamus as playing a role in the production of fever, but few investigations of endogenous neurochemicals have been made during fever. Turnover rates of transmitters utilizing radioactive precursors may be one of the most accurate measurements of activity in brain regions. The present study was designed to measure the turnover of 5-hydroxytryptamine (5-HT) norepinephrine (NE) and dopamine (DA) in the hypothalamus of rats during pyrogen fever. Salmonella typhosa (Wyeth, 8 units) was previously found in our laboratory to produce a significant hyperthermia in most rats by 2.5 hours. This pyrogen (N = l2) or saline control (N = 8) was injected intraperitoneally and the rats killed 2.75 hours later. Rectal temperatures (Tr) were monitored continuously with thermocouples taped to the tail and recorded automatically every 3 minutes. Half of each group received an injection of radioactive precursors, (3)H-tryptophan (0.5 mCi) and (3)H-tryptophan (1.0 mCi), via an indwelling jugular catheter 60 minutes before killing, and the other half at 90 minutes. The rats were killed by near freezing in liquid nitrogen and the brains dissected in the cold. Turnover was measured by the method of Lane (Life Sci 21, 1101, 1977). At the time of killing most of the pyrogen group showed a significant (p pyrogen and saline groups. A significant difference was found in the specific activity of NE between the 60 minute pyrogen and saline groups (4.41 +/- 0.41 vs 2.6 +/- 0.51 dpm/pmole) but no change in turnover. This suggests an increased accumulation of (3)H-NE in the pyrogen group, but no change in utilization. An increased turnover of DA for the pyrogen group (44.5 vs 19.2 pmole/mg protein/hr) was found. However, DA is mainly a precursor in the hypothalamus and measurement was near the limit of sensitivity for the assay; these limitations Must be considered in interpreting this data. The most significant finding was

  14. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Park, Kwang Suk [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea); Seoul National University College of Medicine, Department of Biomedical Engineering, Seoul (Korea); Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul [Seoul National University College of Medicine, Department of Otolaryngology, Head and Neck Surgery, Seoul (Korea); Lee, Dong Soo; Jeong, Jae Min [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea)

    2005-06-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1-{sup 14}C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in

  15. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Park, Kwang Suk; Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul; Lee, Dong Soo; Jeong, Jae Min

    2005-01-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1- 14 C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in any

  16. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus.

    Directory of Open Access Journals (Sweden)

    Patricia Blanchet

    2017-08-01

    Full Text Available Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense. The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms "mental retardation". To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus.

  17. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

    Science.gov (United States)

    Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

    2014-05-28

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

  18. Oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics: Immunofluorescent localization in the mouse hypothalamus.

    Science.gov (United States)

    Anderson, Brian M; Jacobson, Lauren; Novakovic, Zachary M; Grasso, Patricia

    2017-06-01

    This study describes the localization of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics, in the hypothalamus of Swiss Webster and C57BL/6J wild-type mice, leptin-deficient ob/ob mice, and leptin-resistant diet-induced obese (DIO) mice. The mice were given [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in 0.3% dodecyl maltoside by oral gavage. Once peak serum concentrations were reached, the mice received a lethal dose of pentobarbital and were subjected to intracardiac perfusion fixation. The brains were excised, post-fixed in paraformaldehyde, and cryo-protected in sucrose. Free-floating frozen coronal sections were cut at 25-µm and processed for imaging by immunofluorescence microscopy. In all four strains of mice, dense staining was concentrated in the area of the median eminence, at the base and/or along the inner wall of the third ventricle, and in the brain parenchyma at the level of the arcuate nucleus. These results indicate that [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 cross the blood-brain barrier and concentrate in an area of the hypothalamus known to regulate energy balance and glucose homeostasis. Most noteworthy is the localization of [D-Leu-4]-OB3 immunoreactivity within the hypothalamus of DIO mice via a conduit that is closed to leptin in this rodent model, and in most cases of human obesity. Together with our previous studies describing the effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on energy balance, glucose regulation, and signal transduction pathway activation, these findings are consistent with a central mechanism of action for these synthetic peptide leptin mimetics, and suggest their potential usefulness in the management of leptin-resistant obesity and type 2 diabetes in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. In vivo autoradiographic demonstration of β-adrenergic binding sites in adult rat type II alveolar epithelial cells

    International Nuclear Information System (INIS)

    Smith, D.M.; Sidhu, M.K.

    1984-01-01

    Adult male rats were injected intravenously with the muscarinic binding probe 3 H-Quinuclidinyl benzilate (QNB) or the β-adrenergic probe 3 H-dihydroalprenolol (DHA). Other rats were pre-treated with an intraperitoneal injection of a 500-fold excess of L-isoproterenol prior to the DHA. Light microscopic autoradiography of 0.5 μm sections of lung from the QNB group demonstrated very little labelling even after 6 months of exposure. In constrast, trachealis smooth muscle from these animals contained substantial labelling. Autoradiographs of lung from rats injected with DHA demonstrated labelling which was well localized over alveolar septa and concentrated over the cytoplasm of type II cells. Quantitative analysis of labelling in the DHA groups indicated a significant reduction of labelling in animals treated with L-isoproterenol prior to DHA, in both the alveolar parenchyma in general and over type II cells. The results of this study provide morphologic evidence for the uptake and specific binding of β-adrenergic antagonists by the adult lung in vivo, while failing to demonstrate similar binding of a muscarinic probe. In addition, the results demonstrate specific β-adrenergic receptors on type II cells in vivo and substantiate the view of a direct effect of β-adrenergic agonists on alveolar type II cells

  20. Autoradiographic study of the penetration of radiolabelled dextrans and inulin through non-keratinized oral mucosa in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Alfano, M C; Chasens, A I; Masi, C W [Block Periodontal Research Laboratories, Department of Periodontics and Oral Medicine, Fairleigh Dickinson University, School of Dentistry, Hackensack, New Jersey, U.S.A.

    1977-01-01

    Although a well known barrier effect against the penetration of macromolecules exists at the basement membrane region of epithelial tissues, recent reports suggest that the penetration of smaller molecules may be impeded by this region. Considering the probable importance of the permeability of gingival crevicular tissues in the etiology of inflammatory periodontal disease, the present study was designed to evaluate the barrier function of the basement membrane region of non-keratinized oral mucosal epithelium to a series of radiolabelled penetrating molecules of increasing molecular weight. Tritium labeled inulin (Mw 5,000), dextran 20 (Mw 20,000) and dextran 70 (Mw 70,000) were used as penetrating molecules, and autoradiographic tracer techniques were used to evaluate the barrier function. The study was conducted in vitro to eliminate vascular ''wash-out'' effects and to facilitate study of penetration across the basement membrane region in both directions. The results indicated that although the penetration of inulin and dextran 70 was impeded by the basement membrane region, the penetration of dextran 20 was not affected. Therefore, the barrier function of the basement membrane region is not solely dependent on the molecular weight of the penetration molecule. Mechanisms to account for the findings are described and the significance to periodontal disease is discussed.

  1. Biochemical characterization of an autoradiographic method for studying excitatory amino acid receptors using L-[3H]glutamate

    International Nuclear Information System (INIS)

    Cincotta, M.; Summers, R.J.; Beart, P.M.

    1989-01-01

    A method was developed for radiolabeling excitatory amino acid receptors of rat brain with L-[ 3 H]glutamate. Effective labeling of glutamate receptors in slide-mounted 10-microns sections was obtained using a low incubation volume (0.15 ml) and rapid washing: a procedure where high ligand concentrations were achieved with minimal waste. Saturation experiments using [ 3 H]glutamate revealed a single binding site of micromolar affinity. The Bmax was trebled in the presence of Ca2+ (2.5 mM) and Cl- (20 mM) with no change in the Kd. Binding was rapid, saturable, stereospecific, and sensitive to glutamate receptor agonists. The proportions of [ 3 H]glutamate binding sensitive to N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were 34, 54, and 51%, respectively. NMDA inhibited binding at a distinct subset of L-[ 3 H]glutamate sites, whereas AMPA and kainate competed for some common sites. Labeling of sections with L-[ 3 H]glutamate in the presence of the selective agonists allowed autoradiographic visualization of glutamate receptor subtypes in brain tissue

  2. Computer-assisted analyses of (/sup 14/C)2-DG autoradiographs employing a general purpose image processing system

    Energy Technology Data Exchange (ETDEWEB)

    Porro, C; Biral, G P [Modena Univ. (Italy). Ist. di Fisiologia Umana; Fonda, S; Baraldi, P [Modena Univ. (Italy). Lab. di Bioingegneria della Clinica Oculistica; Cavazzuti, M [Modena Univ. (Italy). Clinica Neurologica

    1984-09-01

    A general purpose image processing system is described including B/W TV camera, high resolution image processor and display system (TESAK VDC 501), computer (DEC PDP 11/23) and monochrome and color monitors. Images may be acquired from a microscope equipped with a TV camera or using the TV in direct viewing; the A/D converter and the image processor provides fast (40 ms) and precise (512x512 data points) digitization of TV signal with a 256 gray levels maximum resolution. Computer programs have been developed in order to perform qualitative and quantitative analyses of autoradiographs obtained with the 2-DG method, which are written in FORTRAN and MACRO 11 Assembly Language. They include: (1) procedures designed to recognize errors in acquisition due to possible image shading and correct them via software; (2) routines suitable for qualitative analyses of the whole image or selected regions of it, providing the opportunity for pseudocolor coding, statistics, graphic overlays; (3) programs permitting the conversion of gray levels into metabolic rates of glucose utilization and the display of gray- or color-coded metabolic maps.

  3. Autoradiographic research on cell proliferation of prenatal rat lung cells and their influence using the mitogen Kallikrein

    International Nuclear Information System (INIS)

    Bock-Lamberlin, P.R.

    1980-01-01

    In this work autoradiographic experiments were carried out on the kinetics of proliferation of four cell populations of the prenatal rat lung with the help of the determination of the 3 H-thymidine marker indices, with the following results: 1. The four studied cell populations exhibited variable proliferation rates on the twentieth or twenty-first day of development. 2. The strongest affect of the exogenously applied mitogen Kallikrein was demonstrated on the vessel wall cells, the next strongest on the bronchial epithelial cells, then the cartilage cells and finally the alveolar wall cells. 3. The mitogenic effect is dependent on dose. Higher doses significantly increased the 3 H-thymidine marker indices of the four cell populations tested in this work. 4. When the exposure time of the Kallikrein was extended by one hour this lead partially to stronger mitogenic effects than by the shorter exposure times at the same and higher dose levels of mitogen. 5. The 3 H-thymidine marker indices are dependent on the exposure time. 6. With increasing litter size, the 3 H indices as a rule decrease. (orig./MG) [de

  4. An autoradiographical method using an imaging plate for the analyses of plutonium contamination in a plutonium handling facility

    International Nuclear Information System (INIS)

    Takasaki, Koji; Sagawa, Naoki; Kurosawa, Shigeyuki; Mizuniwa, Harumi

    2011-01-01

    An autoradiographical method using an imaging plate (IP) was developed to analyze plutonium contamination in a plutonium handling facility. The IPs were exposed to ten specimens having a single plutonium particle. Photostimulated luminescence (PSL) images of the specimens were taken using a laser scanning machine. One relatively large spot induced by α-radioactivity from plutonium was observed in each PSL image. The plutonium-induced spots were discriminated by a threshold derived from background and the size of the spot. A good relationship between the PSL intensities of the spots and α-radioactivities measured using a radiation counter was obtained by least-square fitting, taking the fading effect into consideration. This method was applied to workplace monitoring in an actual uranium-plutonium mixed oxide (MOX) fuel fabrication facility. Plutonium contaminations were analyzed in ten other specimens having more than two plutonium spots. The α-radioactivities of plutonium contamination were derived from the PSL images and their relative errors were evaluated from exposure time. (author)

  5. An autoradiographic analysis of the cortical connections of the pallidal and cerebellar zones within the feline motor thalamus

    International Nuclear Information System (INIS)

    Wensel, J.P.

    1989-01-01

    The feline motor thalamus relays both basal ganglia and cerebellar inputs to the motor cortex. This complex is classically subdivided into three nuclei: the ventroanterior nucleus (VA), the ventrolateral nucleus (VL), and the ventromedial nucleus (VM). Poor correlation between recognized patterns of cortical and subcortical connectivity and traditional boundaries used to distinguish these nuclei complicate the elucidation of the role they play in the elaboration of motor behavior. The recent demonstration of complementarity for the pallidothalamic and dentatothalamic projections to the motor thalamus of the cat provided the foundation for a revision of these nuclear borders to reflect differences in subcortical connectivity. Using a revised topography, this study analyzed the afferent and efferent connections of the feline VA and VL through the application of both anterograde and retrograde tracing techniques. The extent of the cerebellothalamic projection, as revealed by the bidirectional transport of WGA-HRP, was used to demarcate the boundary between VA and VL. Injections of tritiated amino acids into VA and VL allowed for the autoradiographic tracing of their cortical projections. Autoradiography was also used to demonstrate the distributions of corticothalamic projections from selected pericruciate and posterior parietal subfields to the motor thalamus

  6. Autoradiographic study of the penetration of radiolabelled dextrans and inulin through non-keratinized oral mucosa in vitro

    International Nuclear Information System (INIS)

    Alfano, M.C.; Chasens, A.I.; Masi, C.W.

    1977-01-01

    Although a well known barrier effect against the penetration of macromolecules exists at the basement membrane region of epithelial tissues, recent reports suggest that the penetration of smaller molecules may be impeded by this region. Considering the probable importance of the permeability of gingival crevicular tissues in the etiology of inflammatory periodontal disease, the present study was designed to evaluate the barrier function of the basement membrane region of non-keratinized oral mucosal epithelium to a series of radiolabelled penetrating molecules of increasing molecular weight. Tritium labeled inulin (Mw 5,000), dextran 20 (Mw 20,000) and dextran 70 (Mw 70,000) were used as penetrating molecules, and autoradiographic tracer techniques were used to evaluate the barrier function. The study was conducted in vitro to eliminate vascular ''wash-out'' effects and to facilitate study of penetration across the basement membrane region in both directions. The results indicated that although the penetration of inulin and dextran 70 was impeded by the basement membrane region, the penetration of dextran 20 was not affected. Therefore, the barrier function of the basement membrane region is not solely dependent on the molecular weight of the penetration molecule. Mechanisms to account for the findings are described and the significance to periodontal disease is discussed. (author)

  7. The sensitivity testing of Wilms' tumors to cytostatic agents with an autoradiographic in vitro short-term test

    International Nuclear Information System (INIS)

    Willnow, U.

    1984-01-01

    Sensitivity of 15 Wilms' tumors in children was tested towards cytostatic agents in vitro by means of an autoradiographic short-term test. Sensitivity was measured as the magnitude of the inhibition of 3 H-thymidine or 3 H-uridine incorporation. The test was performed with Adriamycin, Actinomycin D, Daunomycin, Bleomycin, Cyclophosphamide, Ifosfamide, Trenimon, and Arabinosylcytosine. None of the tumors is resistant to all substances, they are responsive against 2 or more drugs. The most effective drugs tested are Adriamycin, Actinomycin D and Cyclophosphamide. The tumors show a marked individual sensitivity pattern. This behavior is explained mainly by the usually high proliferative activity of Wilms' tumors. The possibilities and limits of long-term and short-term methods for sensitivity testing are discussed critically. For the evaluation of the results of in vitro testing and in vivo effectiveness the close correlation should be considered between the type of cytostatic agent and proliferation kinetics of the tumor, cytostatic agent and effect on tumor metabolism as well as the effect of the cytostatics and the nucleic acid precursors used for the short-term test. Despite the methodological limitations preclinical testing should be preferred to unselected chemotherapy. (author)

  8. Autoradiographic investigations on the prednisolone-induced atrophy and on interdependent reactions in different lymphatic tissues of rabbit

    International Nuclear Information System (INIS)

    Steigueber, F.

    1980-01-01

    Under the application of 3 H-thymidine the method of organ extirpation (thymectomy and appendectomy) was combined with the cell labeling technique. By autoradiographic evaluation of histologic specimens the content of labelled lymphocytes in the examined tissues was determined. Thymus, appendix, subcutaneous lymphatic nodes and spleen were examined. In the thymus the application of prednisolone induced organ atrophy. Appendectomy leads in the thymic marrow to an increase of the mitotic activity. In the appendix the application of prednisolone causes the emptying of basal lymphatic follicles. Thymectomy induces a large increase of the mitotic activity of the lymphatic tissue. Not all lymphatic nodes show identical changes after organ extirpation and after prednisolone application, but considerable differences. Only a decreased proliferation of labled lymphocytes, occuring under prednisolone application, can be detected in the marrow of the mesenteric lymphatic nodes and of the red splenic pulp in the animal with thymectomy. This result is also valid for the marrow of the remaining deep lymphatic nodes, after thymectomy and appendectomy. The lymphocyte counting in the peripheral blood done during prednisolone treatment, does not indicate that the lymphocyte values depend to a notable extent on the previous surgical treatment of the animals. (orig./MG) [de

  9. Localisation of 3H-GABA in the rat olfactory bulb: An in vivo and in vitro autoradiographic study

    International Nuclear Information System (INIS)

    Jaffe, E.H.; Cuello, A.C.; Priestley, J.V.

    1983-01-01

    In an attempt to further clarify the localisation of GABAergic elements in the olfactory bulb we have performed, in vivo and in vitro, autoradiographic studies with 3 H-GABA (#betta#-amino butyric acid) and 3 H-DABA (L-2,4 diamino butyric acid). The results have shown a strong labelling with 3 H-GABA of the glial cells in all the layers of the olfactory bulb. A high concentration of grains was observed in the periglomerular region. The labelling in the external plexiform layer was uniformly distributed in the neuropile with the strongest activity at the level of the dendritic processes of the granule cells, leaving the mitral cell dendrites and cell bodies almost free of grains. 3 H-DABA showed a very similar pattern to 3 H-GABA. When olfactory bulb slices were preincubated with #betta#-alanine the labelling of the glial elements almost disappeared especially at the level of the olfactory nerve layer. The labelling pattern of the other layers of the bulb remained mostly unchanged. This supports the view that a population of periglomerular and granule cells are GABAergic and that #betta#-alanine competes with GABA uptake sites only in glial cells. (orig.)

  10. Autoradiographic imaging of cerebral ischemia using hypoxic marker: Tc-99m-HL91 in animal models

    International Nuclear Information System (INIS)

    Jiang, N.Y.; Zhu, C.S.; Hu, X.K.

    2002-01-01

    Objective: To explore the possibility of Tc-99m-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods: 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected Tc-99m-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Result: The ischemic territory accumulated more Tc-99m-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of Tc-99m-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. Conclusion : Tc-99m-HL91 can be avidly taken up by ischemic penumbra. Tc-99m-HL91 is a potential agent for imaging hypoxic tissue, and Tc-99m-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

  11. Autoradiographic imaging of cerebral ischaemia using hypoxic marker: 99mTc-HL91 in animal models

    International Nuclear Information System (INIS)

    Ningyi, J.; Cansheng, Z.; Xiaoke, H.

    2002-01-01

    Objective: To explore the possibility of 99mTc-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected 99mTc-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Result The ischemic territory accumulated more 99mTc-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of 99mTc-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. Conclusion 99mTc-HL91 can be avidly taken up by ischemic penumbra. 99mTc-HL91 is a potential agent for imaging hypoxic tissue, and 99mTc-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

  12. Sex differences in feeding behavior in rats: the relationship with neuronal activation in the hypothalamus

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2015-03-01

    Full Text Available There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation. Sex differences in feeding seem to occur among species, and responses to fasting (i.e., starvation, gonadal steroids (i.e., testosterone and estradiol, and diet (i.e., western-style diet vary significantly between sexes. The hypothalamus is the center for controlling feeding behavior. We examined the activation of feeding-related peptides in neurons in the hypothalamus. Phosphorylation of cyclic AMP response element-binding protein (CREB is a good marker for neural activation, as is the Fos antigen. Therefore, we predicted that sex differences in the activity of melanin-concentrating hormone (MCH neurons would be associated with feeding behavior. We determined the response of MCH neurons to glucose in the lateral hypothalamic area (LHA and our results suggested MCH neurons play an important role in sex differences in feeding behavior. In addition, fasting increased the number of orexin neurons harboring phosphorylated CREB in female rats (regardless of the estrous day, but not male rats. Glucose injection decreased the number of these neurons with phosphorylated CREB in fasted female rats. Finally, under normal spontaneous food intake, MCH neurons, but not orexin neurons, expressed phosphorylated CREB. These sex differences in response to fasting and glucose, as well as under normal conditions, suggest a vulnerability to metabolic challenges in females.

  13. Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia.

    Science.gov (United States)

    Ihnatko, R; Post, C; Blomqvist, A

    2013-10-01

    Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain's metabolic control centre. The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed littermates was examined using two-dimensional electrophoresis (2-DE)-based comparative proteomics. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. The 2-DE data showed an increased expression of dynamin 1, hexokinase, pyruvate carboxylase, oxoglutarate dehydrogenase, and N-ethylmaleimide-sensitive factor in tumour-bearing mice, whereas heat-shock 70 kDa cognate protein, selenium-binding protein 1, and guanine nucleotide-binding protein Gα0 were downregulated. The expression of several of the identified proteins was similarly altered also in the caloric-restricted pair-fed mice, suggesting an involvement of these proteins in brain metabolic adaptation to restricted nutrient availability. However, the expression of dynamin 1, which is required for receptor internalisation, and of hexokinase, and pyruvate carboxylase were specifically changed in tumour-bearing mice with anorexia. The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.

  14. Stiletto stabbing: penetrating injury to the hypothalamus with hyperacute diabetes insipidus.

    Science.gov (United States)

    Itshayek, Eyal; Gomori, John Moshe; Spektor, Sergey; Cohen, José E

    2010-12-01

    Diabetes insipidus (DI) is a well documented complication observed after traumatic head injuries. We report a case of hyperacute onset DI in a 19-year-old male who sustained a hypothalamic-pituitary injury when he was stabbed in the head with a 30-cm long thin-bladed knife. At CT, our patient showed significant hemorrhagic contusions of the lower hypothalamus. He developed polydipsia, polyuria, and mild hypernatremia in the Emergency Department. Diagnostic digital subtraction angiography showed a hypervascular congestive pituitary gland with prominent draining veins. On the third day his hypernatremia became severe (183mEq/L). He was managed with parenteral fluids and a regimen of intranasal DDAVP (1-desamino 8-d-arginine vasopressin), leading to improved plasmatic sodium levels, urine output, and urinary specific gravity. In patients presenting with hyperacute posttraumatic DI, emergency room physicians and neurosurgeons should rule out direct injury to the hypothalamus and/or the posterior lobe of the pituitary, and initiate early pharmacological treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Characterization of taurine binding, uptake, and release in the rat hypothalamus

    International Nuclear Information System (INIS)

    Hanretta, A.T.

    1985-01-01

    The neurotransmitter criteria of specific receptors, inactivation, and release were experimentally examined for taurine in the hypothalamus. Specific membrane binding and synaptosomal uptake of taurine both displayed high affinity and low affinity systems. The neurotransmitter criterion of release was studied in superfused synaptosomes. Exposure of synaptosomes which had been preloaded with a concentration of [ 3 H]taurine in the high affinity uptake range (1.5 μM) to either 56 mM K + or 100 μM veratridine evoked a Ca 2+ -independent release. Exposure of synaptosomes which had been preloaded with a concentration of [ 3 H]taurine in the low affinity uptake range (2 mM) to 56 mM K + induced a Ca 2+ -independent release, whereas 100 + M veratridine did not, either in the presence or absence of Ca 2+ . Based on these results, as well as other observations, a model is proposed in which the high affinity uptake system is located on neuronal membranes and the low affinity uptake system is located on glial membranes. The mechanisms of binding, uptake, and release in relation to the cellular location of each are discussed. We conclude that the neurotransmitter criterion of activation by re-uptake is satisfied for taurine in the hypothalamus. However, the failure to demonstrate both a specific taurine receptor site and a Ca 2+ -dependent evoked release, necessitates that we conclude that taurine appears not to function as a hypothalamic neurotransmitter, at least not in the classical sense

  16. Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Roberta eHaddad-Tóvolli

    2015-03-01

    Full Text Available Secreted protein Sonic hedgehog (Shh ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR of transcription factors Gli2 and Gli3. This balance—the Shh-Gli code—is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e. we wanted to clarify the hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: 1 hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; 2 another source of diversity are differential requirements for Shh of neural vs non-neural origin; 3 Gli2 is indispensable for the specification of a medial progenitor domain generating several essential hypothalamic nuclei plus the pituitary and median eminence; 4 the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

  17. Reactive oxygen species in the paraventricular nucleus of the hypothalamus alter sympathetic activity during metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    JOSIANE CAMPOS CRUZ

    2015-12-01

    Full Text Available The paraventricular nucleus of the hypothalamus (PVN contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II, which activates AT1 receptors in the circumventricular organs (OCVs, mainly in the subfornical organ (SFO. Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS, leading to increases in sympathetic nerve activity (SNA. Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS: dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS.

  18. Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure.

    Directory of Open Access Journals (Sweden)

    Ju Hwan Kim

    Full Text Available The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs. EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF of 835 MHz at a specific absorption rate (SAR of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress.

  19. The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

    International Nuclear Information System (INIS)

    Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.; Muskhelishvili, L.; Warbritton, A.R.; Thomas, M.; Tareke, E.; McDaniel, L.P.; Doerge, D.R.

    2008-01-01

    Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that is neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor α and β, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk

  20. The effect of radioactive radiation of the neurotransmitter levels in the hypothalamus, pituitary and pineal glands of sheeps

    International Nuclear Information System (INIS)

    Pastorova, B.; Maracek, I.; Stanikova, A.; Halagan, J.; Sopkova, D.

    2006-01-01

    The effect of the exposure of the whole body to continuous radiation was studied of catecholamines (epinephrine and unepinephrine) in the hypothalamus, pineal and pituitary glands of ewes during the anestric period with synchronized oestrus. The radiation was provided at the rate 0.020 Gy per hour. Catecholamines were separated from the tissue supernatants by the absorption chromatographic method and the catecholamine contents in the eluates were determined spectrofluorometrically. Protracted exposure to gamma radiation and hormone stimulation with SG reduces the concentration of unepinephrine (P<0.001) in the whole hypothalamus of the sheep. A statistically significant decrease (P<0.001) was recorded in the medial and caudal hypothalamus of ewes. If is assumed that the decrease in catecholamine concentration after irradiation (2.4 Gy) is associated with the destroyed metabolism of catecholamines in nervous tissue and activity its degradation enzyme monoaminooxidase. (authors)

  1. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model

    Science.gov (United States)

    Canelles, Sandra; Argente, Jesús; Barrios, Vicente

    2016-01-01

    ABSTRACT Insulin receptor substrate-2-deficient (IRS2−/−) mice are considered a good model to study the development of diabetes because IRS proteins mediate the pleiotropic effects of insulin-like growth factor-I (IGF-I) and insulin on metabolism, mitogenesis and cell survival. The hypothalamus might play a key role in the early onset of diabetes, owing to its involvement in the control of glucose homeostasis and energy balance. Because some inflammatory markers are elevated in the hypothalamus of diabetic IRS2−/− mice, our aim was to analyze whether the diabetes associated with the absence of IRS2 results in hypothalamic injury and to analyze the intracellular mechanisms involved. Only diabetic IRS2−/− mice showed increased cell death and activation of caspase-8 and -3 in the hypothalamus. Regulators of apoptosis such as FADD, Bcl-2, Bcl-xL and p53 were also increased, whereas p-IκB and c-FLIPL were decreased. This was accompanied by increased levels of Nox-4 and catalase, enzymes involved in oxidative stress. In summary, the hypothalamus of diabetic IRS2−/− mice showed an increase in oxidative stress and inflammatory markers that finally resulted in cell death via substantial activation of the extrinsic apoptotic pathway. Conversely, non-diabetic IRS2−/− mice did not show cell death in the hypothalamus, possibly owing to an increase in the levels of circulating IGF-I and in the enhanced hypothalamic IGF-IR phosphorylation that would lead to the stimulation of survival pathways. In conclusion, diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID:27013528

  2. Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2-adrenoceptors

    Science.gov (United States)

    Wortley, K E; Heal, D J; Stanford, S C

    1999-01-01

    The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely-moving rats were investigated using microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.In both the cortex and hypothalamus, pretreatment of rats with the α2-adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2-adrenoceptors. Furthermore, the data suggest that terminal α2-adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex. PMID:10516646

  3. Sex differences in androgen receptors of the human mamillary bodies are related to endocrine status rather than to sexual orientation or transsexuality

    NARCIS (Netherlands)

    Kruijver, F. P.; Fernández-Guasti, A.; Fodor, M.; Kraan, E. M.; Swaab, D. F.

    2001-01-01

    In a previous study we found androgen receptor (AR) sex differences in several regions throughout the human hypothalamus. Generally, men had stronger nuclear AR immunoreactivity (AR-ir) than women. The strongest nuclear labeling was found in the caudal hypothalamus in the mamillary body complex

  4. Histological changes in the hypothalamus and ependyne in the third ventricle of the brain in sheep after irradiation

    International Nuclear Information System (INIS)

    Stanikova, A.; Pastorova, B.

    2008-01-01

    We focused on changes in the hypothalamic neuro-secretion, morphology of brain ventricle ependyma of sheep after irradiation and hormonal stimulation. We observed sheep in anoestrous. Synchronization was ensured with Agelin for 10 days. On day 5 after instilation of sponges, we started with irradiation lasting for 5 days (2.5 Gy) and on day 10 we stimulated the sheep with SG and FSH. The samples from hypothalamus intended for REM, were processed according to Murakami et al. (1977). Hormonal treatment in combination with irradiation produced qualitative changes, more marked in the ependyma than in the hypothalamus. (authors)

  5. Morphological changes in the neurons of hypothalamus and ependyma of the third cerebral ventricle of sheep after irradiation

    International Nuclear Information System (INIS)

    Stanikova, A.; Pastorova, B.; Maracek, I.; Sopkova, D.; Halagan, J.

    2004-01-01

    We focused on changes in the hypothalamic neuro-secretion, morphology of brain ventricle ependyma of sheep after irradiation and hormonal stimulation. We observed sheep in anoestrus. Synchronization was ensured with Agelin for 10 days. On day 5 after the instillation of sponges, we started with irradiation lasting for 5 days (2.5 Gy) and on day 10 we stimulated the sheep with SG and FSH. The samples from hypothalamus intended for REM, were processed according to Murakami et al. (1977). Hormonal treatment in combination with irradiation produced qualitative changes, more marked in the ependyma than in the hypothalamus. (authors)

  6. Autoradiographic studies of the distribution of radium-226 in rat bone: their implications for human radiation dosimetry and toxicity

    International Nuclear Information System (INIS)

    Priest, N.D.; Haines, J.W.; Howells, G.; Green, D.

    1983-01-01

    A solution containing 226 Ra chloride was injected into young female rats via the saphenous vein. Subsequently, the distribution and retention of the 226 Ra in the skeleton was studied. The results show that 226 Ra is initially deposited in the rat femur as a volume deposit and is fairly evenly distributed throughout the bone matrix. Much of the 226 Ra initially deposited in the skeleton is lost within a few days of its administration. During the first week 226 Ra gradually accumulates at sites of bone deposition including accreting surfaces. Subsequent bone growth results in the burial of contaminated bone surfaces. Following bone resorption some of the 226 Ra released from individual bones is recycled systemically so that all skeletal components tend towards a uniform 226 Ra concentration per unit of bone mineral. Of the two models conventionally used for radiation dosimetry purposes, these results reported for rats suggest that though neither is ideal, the volume distribution model is preferable to the surface model at all times after the uptake of radium by the skeleton. (author)

  7. The role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

    Science.gov (United States)

    Harris, Breanna N; Carr, James A

    2016-05-01

    Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Opioid systems in the lateral hypothalamus regulate feeding behavior through orexin and GABA neurons.

    Science.gov (United States)

    Ardianto, C; Yonemochi, N; Yamamoto, S; Yang, L; Takenoya, F; Shioda, S; Nagase, H; Ikeda, H; Kamei, J

    2016-04-21

    The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of μ-, δ- and κ-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3 mg/kg, s.c.) and selective μ- (β-funaltrexamine, β-FNA; 10 mg/kg, s.c.), δ- (naltrindole; 3 mg/kg, s.c.) and κ- (norbinaltorphimine, norBNI; 20 mg/kg, s.c.) opioid receptor antagonists significantly decreased food intake in food-deprived mice. The injection of naloxone (20 μg/side) into the LH significantly decreased food intake whereas the injection of naloxone (20 μg/side) outside of the LH did not affect food intake. The injection of β-FNA (2 μg/side), naltrindole (1 μg/side) or norBNI (2 μg/side) into the LH significantly decreased food intake. Furthermore, all these antagonists significantly decreased the mRNA level of preproorexin, but not those of other hypothalamic neuropeptides. In addition, the injection of the GABAA receptor agonist muscimol (5 μg/side) into the LH significantly decreased food intake, and this effect was abolished by the GABAA receptor antagonist bicuculline (50 μg/side). Muscimol (1mg/kg, i.p.) decreased the mRNA level of preproorexin in the hypothalamus. Naloxone (3mg/kg, s.c.) significantly increased the GABA level in the LH and both bicuculline and the GABA release inhibitor 3-mercaptopropionic acid (3-MP, 5 μg/side) attenuated the inhibitory effect of naloxone on feeding behavior. 3-MP also attenuated the effects of β-FNA and norBNI, but not that of naltrindole. These results show that opioid systems in the LH regulate feeding behavior through orexin neurons. Moreover, μ- and κ-, but not δ-, opioid receptor antagonists inhibit feeding behavior by activating GABA neurons in the LH. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Autoradiographic observations of the induced vascular injuries by arachidonic acid in rabbit's brain and lung using 111In-oxine labeled platelets

    International Nuclear Information System (INIS)

    Fujimoto, Tsukasa; Fukushima, Yoshiharu; Suzuki, Hidenori; Kuroiwa, Kyoko; Tanoue, Kenjiro; Yamazaki, Hiroh.

    1985-01-01

    Autoradiography using 111 In-oxine labeled autologous platelets was performed to observe the behavior of platelets in induced vascular injury by activated platelets in rabbit's brain and lung. Cerebrovascular injuries were induced by injection of arachidonic acid (AA) (0.7 mg/kg) into right internal carotid artery. Fourteen animals were pretreated with antiplatelet drug, ticlopidine (200 mg/kg) and 10 were controls. Before the AA injection, 111 In-oxine (300 μCi) labeled platelets were injected intravenously. Evans blue was given as a marker of disturbances of blood brain barrier. Sixty min after the AA injection, brains were removed and autoradiographic and electron microscopic studies were done. In the nontreated animals and some of the treated animals whose platelet aggregability was not suppressed, blue staining were seen in the cerebral hemisphere of injection side and hot radioactivity in autoradiogram were revealed in corresponding area. In the treated animals whose platelet aggregability was remarkably suppressed, no or slight blue staining or radioactivity were recognized. Only in hot radioactive area, platelet thrombi and vascular injuries were seen. Vascular injuries of lung were produced by decompression after keeping animals under hyperbalic condition (6 atomosphere absolute for 40 min). Before this procedure, 111 In-oxine labeled platelets were injected. Lungs of both 4 control and 4 decompression sickness animals were removed and autoradiographic and lightmicroscopic observations were performed. In lungs of decompression sickness animals remarkable spotty high radioactivity and prominent platelet aggregates in the vessels were seen. These findings were not seen in control animals. Our results suggested important roles of platelets in induced vascular injuries. And this autoradiographic approach seemed to be quite useful for observation of platelet's behavior in injured vessels and evaluation of antiplatelet drugs. (author)

  10. Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

    Science.gov (United States)

    Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

    2007-09-15

    Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

  11. Macronutrients and the FTO gene expression in hypothalamus; a systematic review of experimental studies

    Directory of Open Access Journals (Sweden)

    Saeid Doaei

    2017-03-01

    Full Text Available The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.

  12. Hypothalamus-pituitary-thyroid axis activity and function of cardiac muscle in energy deficit

    Directory of Open Access Journals (Sweden)

    Katarzyna Lachowicz

    2017-12-01

    Full Text Available Frequently repeated statement that energy restriction is a factor that improves cardiovascular system function seems to be not fully truth. Low energy intake modifies the hypothalamus-pituitary-thyroid axis activity and thyroid hormone peripheral metabolism. Thyroid hormones, as modulators of the expression and activity of many cardiomyocyte proteins, control heart function. Decreased thyroid hormone levels and their disturbanced conversion and action result in alternation of cardiac remodeling, disorder of calcium homeostasis and diminish myocardial contractility. This review provides a summary of the current state of knowledge about the mechanisms of energy restriction effects on thyroidal axis activity, thyroid hormone peripheral metabolism and action in target tissues, especially in cardiac myocytes. We also showed the existence of energy restriction-thyroid-heart pathway.

  13. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Juan P. Hernández-Fonseca

    2009-01-01

    Full Text Available Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.

  14. State-dependent cellular activity patterns of the cat paraventricular hypothalamus measured by reflectance imaging

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, D M; Poe, G R

    1996-01-01

    Activity within the cat paraventricular hypothalamus (PVH) during sleep and waking states was measured by quantifying intrinsic tissue reflectivity. A fiber optic probe consisting of a 1.0 mm coherent image conduit, surrounded by plastic fibers which conducted 660 nm source light, was attached...... to a charge-coupled device camera, and positioned over the PVH in five cats. Electrodes for assessing state variables, including electroencephalographic activity, eye movement, and somatic muscle tone were also placed. After surgical recovery, reflected light intensity was measured continuously at 2.5 Hz...... changes with behavioral state in a regionally specific manner, and that overall activity increases during quiet sleep, and is even more enhanced in active sleep. PVH activation could be expected to stimulate pituitary release of adrenocorticotropic hormone (ACTH) and affect input to autonomic regulatory...

  15. Calcium in pollen-pistil interaction in Petunia hybrida Hort. I. Localization of Ca2+ ions in mature pollen grain using pyroantimonate and autoradiographic methods.

    Science.gov (United States)

    Bednarska, E; Butowt, R

    1994-01-01

    The localization of Ca2+ in the mature pollen grain and the flow of these ions from the somatic tissues of the anther to the pollen grains has been studied using pyroantimonate and autoradiographic methods. In the pollen grain, Ca2+ ions have been localized in the sporoderm and in the cytoplasmic vesicles of probably dictyosomal origin. Calcium ions were transported into the sporoderm together with the compounds of degenerating tapetum. The material of degenerating tapetum forms pollen coat surrounding the mature pollen grain.

  16. Calcium in pollen-pistil interaction in 'Petunia hybrida Hor'. Pt. 1. Localization of Ca2+ ions in mature pollen grain using pyroantimonate and autoradiographic methods

    International Nuclear Information System (INIS)

    Bednarska, E.; Butowt, R.

    1994-01-01

    The localization of Ca 2+ in the mature pollen grain and the flow of these ions the somatic tissues of the anther to the pollen grains has been studied using pyroantimonate and autoradiographic methods. In the pollen grain, Ca 2+ ions have been localized in the sporoderm in the cytoplasmic vesicles of probably dictyosomal origin. Calcium ions were transported into the sporoderm together with the compounds of degenerating tapetum. The material of degenerating tapetum forms pollen coat surrounding the mature pollen grains. (author). 18 refs, 9 figs

  17. Calcium in pollen-pistil interaction in `Petunia hybrida Hor`. Pt. 1. Localization of Ca{sup 2+} ions in mature pollen grain using pyroantimonate and autoradiographic methods

    Energy Technology Data Exchange (ETDEWEB)

    Bednarska, E.; Butowt, R. [Uniwersytet Mikolaja Kopernika, Torun (Poland)

    1994-12-31

    The localization of Ca{sup 2+} in the mature pollen grain and the flow of these ions the somatic tissues of the anther to the pollen grains has been studied using pyroantimonate and autoradiographic methods. In the pollen grain, Ca{sup 2+} ions have been localized in the sporoderm in the cytoplasmic vesicles of probably dictyosomal origin. Calcium ions were transported into the sporoderm together with the compounds of degenerating tapetum. The material of degenerating tapetum forms pollen coat surrounding the mature pollen grains. (author). 18 refs, 9 figs.

  18. Significance of local cerebral glucose utilization determined by the autoradiographic (/sup 14/C)deoxyglucose method in experimentally induced coma

    Energy Technology Data Exchange (ETDEWEB)

    Sakurada, O.; Kobayashi, M.; Ueno, H.; Ishii, S. (Juntendo Univ., Tokyo (Japan). School of Medicine)

    1982-01-01

    Bilateral lesions made in the midbrain reticular formation of the rat produced behavioral akinesia. These animals neither ate nor drank. EEGs of these animals usually showed high voltage slow waves at rest. Slight EEG arousal response was demonstrated by clapping, touching and pinching only in rats with moderate impairment. Concerning the rates of local cerebral glucose utilization (LCGU) measured by means of the autoradiographic (/sup 14/C) deoxyglucose method, 13 structures exhibited significant reductions in 28 gray structures examined when compared with sham operated rats. Lesions in the midbrain reticular formation resulted in reduction of LCGU in the neocortex, ventral nucleus of the thalamus, subthalamic nucleus, and medial and lateral geniculated bodies, mamillary body, septal nucleus and caudateputamen. Structures which did not show any significant change in LCGU were those related to the paleo and archi-cortices. These findings suggest the existence of two types of ascending activating systems. Administration of 30 mg/kg of pentobarbital reduced LCGU diffusely throughout the brain. When thyrotropin releasing hormone (TRH) was administered to rats with lesions in the midbrain reticular formation, reversal of the reduction of LCGU was observed in the dorsomedial nucleus of the thalamus and the mamillary body. Reversal of LCGU in the dorsomedial nucleus of thalamus was especially significant and its level exceeded the level of the sham control value. This suggests TRH might exert its function through the dorsomedial nucleus of the thalamus and mamillary body. When TRH was administered to rats treated with pentobarbital, significant reversal was observed in the following structures: the lateral and ventral nucleus of the thalamus, dentate gyrus, caudate-putamen, nucleus accumbens, pontine gray matter, and raphe nucleus.

  19. The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand

    Energy Technology Data Exchange (ETDEWEB)

    Basile, A.S.; Ostrowski, N.L.; Gammal, S.H.; Jones, E.A.; Skolnick, P. (National Institutes of Health, Bethesda, MD (USA))

    1990-02-01

    Autoradiographic analysis was used to examine radioligand binding to benzodiazepine (BZ) and GABAA receptors in the brains of rabbits with hepatic encephalopathy (HE). Thin sections of whole brain from normal rabbits and rabbits with HE were mounted on slides and subdivided into two groups. One group was washed before incubation with radioligand, while the second group was not prewashed. (3H)Flunitrazepam binding to BZ receptors was decreased by 22% to 42% (p less than 0.05) in the cerebral cortex, superior and inferior colliculi, and cerebellum of unwashed sections from rabbits with HE compared to all other groups. The binding of (3H)Ro 15-1788 to unwashed sections from rabbits with HE was reduced by a similar degree (18% to 37%, p less than 0.05) in the cerebral cortex, hippocampus, superior colliculus, and cerebellar cortex. Incubation of sections with the GABA-mimetic muscimol and NaCl produced an additional decrease in (3H)flunitrazepam binding to the cortex and hippocampus (25% to 31%, p less than 0.05) in unwashed HE rabbit brain, but increased radioligand binding (27% to 71%, p less than 0.05) to several regions in control rabbits. No changes in radioligand binding to either GABAA or peripheral benzodiazepine receptors was observed between HE and control rabbit sections. These findings are consistent with previous electrophysiologic and neurochemical observations indicating no significant changes in either the function or density of GABAA or BZ receptors in this model of HE. Further, they indicate that a reversible BZ receptor ligand with agonist properties is present in the brain in HE. This substance may contribute to the enhancement of GABAergic tone observed in this syndrome.

  20. Corticotropin-releasing factor (CRF) receptors in intermediate lobe of the pituitary: Biochemical characterization and autoradiographic localization

    International Nuclear Information System (INIS)

    Grigoriadis, D.E.; De Souza, E.B.

    1989-01-01

    CRF receptors were characterized using radioligand binding and chemical affinity cross-linking techniques and localized using autoradiographic techniques in porcine, bovine and rat pituitaries. The binding of 125I-[Tyr0]-ovine CRF (125I-oCRF) to porcine anterior and neurointermediate lobe membranes was saturable and of high affinity with comparable KD values (200-600 pM) and receptor densities (100-200 fmoles/mg protein). The pharmacological rank order of potencies for various analogs and fragments of CRF in inhibiting 125I-oCRF binding in neurointermediate lobe was characteristic of the well-established CRF receptor in anterior pituitary. Furthermore, the binding of 125I-oCRF to both anterior and neurointermediate lobes of the pituitary was guanine nucleotide-sensitive. Affinity cross-linking studies revealed that the molecular weight of the CRF binding protein in rat intermediate lobe was identical to that in rat anterior lobe (Mr = 75,000). While the CRF binding protein in the anterior lobes of porcine and bovine pituitaries had identical molecular weights to CRF receptors in rat pituitary (Mr = 75,000), the molecular weight of the CRF binding protein in porcine and bovine intermediate lobe was slightly higher (Mr = 78,000). Pituitary autoradiograms from the three species showed specific binding sites for 125I-oCRF in anterior and intermediate lobes, with none being apparent in the posterior pituitary. The identification of CRF receptors in the intermediate lobe with comparable characteristics to those previously identified in the anterior pituitary substantiate further the physiological role of CRF in regulating intermediate lobe hormone secretion

  1. Differential effects of axotomy on immature and mature hamster facial neurons: a tritiated-uridine autoradiographic study

    International Nuclear Information System (INIS)

    Jones, K.J.; LaVelle, A.

    1987-01-01

    In this study, tritiated-uridine incorporation was autoradiographically examined following axotomy of hamster facial motor neurons (HFMN) at the critical development age of 15 days postnatal and in the adult. The postoperative times selected were 0.5, 1, 2, and 4 days. In the 15-day operative series, no changes in incorporation were observed at any of the postoperative times, except at 4 days postoperative, when there was a decrease in tritiated-uridine incorporation in the axotomized neurons relative to the controls. In the adult operative series there were no changes in incorporation at 0.5 or 1 day postoperative, relative to the controls. At 2 days postoperative in the adult, there was a transient increase in tritiated-uridine incorporation that returned to control levels by 4 days postoperative. When axotomized and control cytoplasmic/nuclear grain densities were compared, no changes were found in either operative series. These results of the time course of axotomy-induced changes in RNA synthesis in HFMN corroborate our previous findings of an age-dependent reactive sequence in HFMN and lend support to the hypothesis that the young neurons are synthesizing at peak capacity related to final growth and cannot be stimulated further by axotomy. As discussed, the transient increase in RNA levels in the adult, the lack of any changes in the rate of transfer of RNA from the nucleus to the cytoplasm, and the decrease in RNA levels in the 15-day neurons may be related to the presence of an unusual intranucleolar body within the nucleolus of HFMN that contains ribosomal precursors

  2. Autoradiographic imaging of cerebral ischemia using hypoxic marker: 99mTc-HL91 in animal models

    International Nuclear Information System (INIS)

    Zhu Cansheng; Jiang Ningyi; Hu Xiaoke

    2001-01-01

    Objective: To explore the possibility of 99m Tc-HL91 imaging in detecting the ischemic penumbra during acute stoke. Methods; 16 Sprague-Dawley (SD) rats were divided into operation group (n=12) and pseudo-operation group (n=4) randomly. In operation group, 12 middle cerebral artery occlusion animal (MCAO) models were established by electrocautery. 4 rats in pseudo-operation group were treated as a control without occlusion. All animals were injected 99m Tc-HL91 intravenously 2 hours after occlusion. Animals were killed at different time after injection and brains were removed rapidly from the skull to do the autoradiographic study. Results: The ischemic territory accumulated more 99m Tc-HL91 than the opposite site in the autoradiogram at 1 hour after injection. The ischemic cerebral tissue can be visualized clearly. At 2, 4 hours after injection, the difference of accumulation of 99m Tc-HL91 in target and non-target site became more obvious. By using computer-enhanced imaging analysis, the optical density (OD) ratio differences between each subgroup of operation group and pseudo-operation group were all significant. The OD ratios (T/N) were 1.2691±0.0189, 1.3542±0.0119, 2.1201±0.0616, 2.5369±0.1214 respectively at 1, 2, 4 hours after 99m Tc-HL91 injection. Conclusion: 99m Tc-HL91 can be avidly taken up by ischemic penumbra. 99m Tc-HL91 is a potential agent for imaging hypoxic tissue, and 99m Tc-HL91 SPECT may be a promising imaging method in detecting the ischemic penumbra

  3. Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study.

    Science.gov (United States)

    Joffe, Hadine; Deckersbach, Thilo; Lin, Nancy U; Makris, Nikos; Skaar, Todd C; Rauch, Scott L; Dougherty, Darin D; Hall, Janet E

    2012-09-01

    Hot flashes are a common side effect of adjuvant endocrine therapies (AET; leuprolide, tamoxifen, aromatase inhibitors) that reduce quality of life and treatment adherence in breast cancer patients. Because hot flashes affect only some women, preexisting neurobiological traits might predispose to their development. Previous studies have implicated the insula during the perception of hot flashes and the hypothalamus in thermoregulatory dysfunction. The aim of the study was to understand whether neurobiological factors predict hot flashes. [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans coregistered with structural magnetic resonance imaging were used to determine whether metabolic activity in the insula and hypothalamic thermoregulatory and estrogen-feedback regions measured before and in response to AET predict hot flashes. Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. We measured regional cerebral metabolic rate of glucose uptake (rCMRglu) in the insula and hypothalamus on FDG-PET. Of 18 women without hot flashes who began AET, new-onset hot flashes were reported by 10 (55.6%) and were detected objectively in nine (50%) participants. Prior to the use of all AET, rCMRglu in the insula (P ≤ 0.01) and hypothalamic thermoregulatory (P = 0.045) and estrogen-feedback (P = 0.007) regions was lower in women who reported developing hot flashes. In response to AET, rCMRglu was further reduced in the insula in women developing hot flashes (P ≤ 0.02). Insular and hypothalamic rCMRglu levels were lower in intermediate than extensive CYP2D6 metabolizers. Trait neurobiological characteristics predict hot flashes. Genetic variability in CYP2D6 may underlie the neurobiological predisposition to hot flashes induced by AET.

  4. Nutritional status affects the microRNA profile of the hypothalamus of female sheep.

    Science.gov (United States)

    Yang, Heng; Lin, Shan; Lei, Xiaoping; Yuan, Cong; Yu, Yaosheng; Zhao, Zongsheng; Chen, Jingbo

    2018-01-25

    Recent studies on the seasonal regulation of the oestrous cycle in sheep have focussed mainly on the responses to photoperiod. However, the brain systems that control reproductive activity also respond to nutritional inputs, although the molecular mechanisms involved are not completely understood. One possibility is that small, non-coding RNAs, such as micro-RNAs (miRNAs), have significant influence. In the present study, the amounts and characteristics of miRNAs in hypothalamus from oestrous and anestrous ewes, fed low- or high-nutrient diets, were compared using Illumina HiSeq sequencing technology. In total, 398 miRNAs, including 261 novel miRNAs, were identified in ewes with an enhanced nutritional status (HEN), whereas 384 miRNAs, including 247 novel miRNAs, were identified in the ewes with a lesser nutritional status (HAN). There were eight conserved and 140 novel miRNAs expressed differentially between the two libraries. Based on quantitative real-time polymerase chain reaction, six miRNAs were assessed to verify the accuracy of the library database. Moreover, the correlation between the miRNA target and several upstream and downstream genes in the oestrus-related pathways were also verified in hypothalamus nerve cells. According to the results, nutritional status plays an important role in oestrous regulation in sheep, and the hypothalamic processes and pathways induced by nutritional signals (folic acid and tyrosine) are different from those induced by photoperiodic regulation of oestrus. We have expanded the repertoire of sheep miRNAs that could contribute to the molecular mechanisms that regulate the initiation of oestrous cycles in anestrous ewes in response to the influence of nutritional status.

  5. Topography of somatostatin gene expression relative to molecular progenitor domains during ontogeny of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Nicanor eMorales-Delgado

    2011-02-01

    Full Text Available The hypothalamus comprises alar, basal and floor plate developmental compartments. Recent molecular data support a rostro-caudal subdivision into rostral (terminal and caudal (peduncular halves. In this context, the distribution of neuronal populations expressing somatostatin (Sst mRNA was analyzed in the developing mouse hypothalamus, comparing with the expression pattern of the genes Orthopedia (Otp, Distal-less 5 (Dlx5, Sonic Hedgehog (Shh and Nk2 homeobox 1 (Nkx2.1. At embryonic day 10.5 (E10.5, Sst mRNA was first detectable in the anterobasal nucleus, a Nkx2.1-, Shh- and Otp- positive basal domain. By E13.5, nascent Sst expression was also related to two additional Otp-positive domains within the alar plate and one in the basal plate. In the alar plate, Sst-positive cells were observed in rostral and caudal ventral subdomains of the Otp-positive paraventricular complex. An additional basal Sst-expressing cell group was found within a longitudinal Otp-positive periretromamillary band that separates the retromamillary area from tuberal areas. Apart of subsequent growth of these initial populations, at E13.5 and E15.5 some Sst-positive derivatives migrate tangentially into neighboring regions. A subset of cells produced at the anterobasal nucleus disperses ventralwards into the shell of the ventromedial hypothalamic nucleus and the arcuate nucleus. Cells from the rostroventral paraventricular subdomain reach the suboptic nucleus, whereas a caudal contingent migrates radially into lateral paraventricular, perifornical and entopeduncular nuclei. Our data provide a topologic map of molecularly-defined progenitor areas originating a specific neuron type during early hypothalamic development. Identification of four main separate sources helps to understand causally its complex adult organization.

  6. Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: a case study with the organochlorine pesticide dieldrin.

    Science.gov (United States)

    Martyniuk, Christopher J; Doperalski, Nicholas J; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2013-01-01

    Organochlorine pesticides (OCPs) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates. In this study, female and male largemouth bass (Micropterus salmoides) (LMB) were exposed to 3mg dieldrin/kg feed in a 2 month feeding exposure (August-October) to (1) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; (2) characterize cell signaling cascades underlying dieldrin neurotoxicity; and (3) determine whether or not co-feeding with 17β-estradiol (E(2)), a hormone with neuroprotective roles, mitigates responses in males to dieldrin. Despite also being a weak estrogen, dieldrin treatments did not elicit changes in reproductive endpoints (e.g. gonadosomatic index, vitellogenin, or plasma E(2)). Sub-network (SNEA) and gene set enrichment analysis (GSEA) revealed that neuro-hormone networks, neurotransmitter and nuclear receptor signaling, and the activin signaling network were altered by dieldrin exposure. Most striking was that the majority of cell pathways identified by the gene set enrichment were significantly increased in females while the majority of cell pathways were significantly decreased in males fed dieldrin. These data suggest that (1) there are sexually dimorphic responses in the teleost hypothalamus; (2) neurotransmitter systems are a target of dieldrin at the transcriptomics level; and (3) males co-fed dieldrin and E(2) had the fewest numbers of genes and cell pathways altered in the hypothalamus, suggesting that E(2) may mitigate the effects of dieldrin in the central nervous system. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease

    International Nuclear Information System (INIS)

    Desjardins, G.C.; Beaudet, A.; Brawer, J.R.

    1990-01-01

    The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat

  8. Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease

    Energy Technology Data Exchange (ETDEWEB)

    Desjardins, G.C.; Beaudet, A.; Brawer, J.R. (McGill Univ., Quebec (Canada))

    1990-12-01

    The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.

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

    Directory of Open Access Journals (Sweden)

    Istvan Toth

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

  10. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Autoradiographic visualization of insulin-like growth factor-II receptors in rat brain

    International Nuclear Information System (INIS)

    Mendelsohn, L.G.; Kerchner, G.A.; Clemens, J.A.; Smith, M.C.

    1986-01-01

    The documented presence of IGF-II in brain and CSF prompted us to investigate the distribution of receptors for IGF-II in rat brain slices. Human 125 -I-IGF-II (10 pM) was incubated for 16 hrs at 4 0 C with slide-mounted rat brain slices in the absence and presence of unlabeled human IGF-II (67 nM) or human insulin (86 nM). Slides were washed, dried, and exposed to X-ray film for 4-7 days. The results showed dense labeling in the granular layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (pyramidal cells CA 1 -CA 2 and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding of these brain regions while insulin produced only a minimal reduction in the amount of 125 I-IGF-II bound. These results indicate that a specific neural receptor for IGS-II is uniquely distributed in rat brain tissue and supports the notion that this peptide might play an important role in normal neuronal functioning

  12. Influence of radon (222Rn) on hypothalamus, hypophysis, ovaries and uterus in Balb C strain mice

    International Nuclear Information System (INIS)

    Koziorowski, A.

    1997-01-01

    Curative properties of radon waters have been applied in balneotherapy for a long time. Therapeutic action is connected with radioactive properties of radon and the products of its degradation. All of them are the source of ionizing radiation, the alpha rays in particular. Radon therapy is widely applied to the treatment of many illnesses, especially of the circulatory system, rheumatism, and arthritis, bronchial asthma and many others. Good therapeutic results have also been achieved in gynecology to mention chronic inflammation of female reproductive organs and endocrinological disorders (of the ovary and during the period of sterilization). Positive results of radon therapy can also be associated with the influence of ionizing radiation on the activity of endocrine glands, mainly the axis hypothalamus - hypophysis - adrenal gland - ovary. There has been neither regular investigation into this problem nor into the morphology of the organs mentioned above. The present paper is an attempt to evaluate the influence of radon inhalations on the structure and function of hypothalamus, hypophysis ovary and uterus. This investigation was performed on hypothalamus, hypophysis, ovary and uterus in Balb C virgin mice. The total population of the mice under study was 140; with a control group of 40. The mice inhalated radon for 30 min. a day, starting with a single irradiation up to a 30-fold. I applied traditional histological techniques and immunocytochemical localization of selected hormones (FSH, LH, ADH). I also tried to evaluate the quantitative activity of mentioned glands by means of the computer morphometric and densitometric analyses of the immunocytochemical slides using an image analyzer Vidas 25 manufactured by Kontron. The results underwent statistical analysis. In order to examine the uterus the ultrastructural evaluation of its functioning was made. Moreover, I analyzed the concentration of FSH, LH, estrogens and progesterone in the serum by means of the

  13. Defective functional connectivity between posterior hypothalamus and regions of the diencephalic-mesencephalic junction in chronic cluster headache.

    Science.gov (United States)

    Ferraro, Stefania; Nigri, Anna; Bruzzone, Maria Grazia; Brivio, Luca; Proietti Cecchini, Alberto; Verri, Mattia; Chiapparini, Luisa; Leone, Massimo

    2018-01-01

    Objective We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16). Random-effect analyses were performed to study differences between patients and controls in ipsilateral and contralateral-to-the-pain posterior hypothalamus functional connectivity. Results Cluster headache patients showed an increased functional connectivity between the ipsilateral posterior hypothalamus and a number of diencephalic-mesencephalic structures, comprising ventral tegmental area, dorsal nuclei of raphe, and bilateral substantia nigra, sub-thalamic nucleus, and red nucleus ( p cluster headache patients mainly involves structures that are part of (i.e. ventral tegmental area, substantia nigra) or modulate (dorsal nuclei of raphe, sub-thalamic nucleus) the midbrain dopaminergic systems. The midbrain dopaminergic systems could play a role in cluster headache pathophysiology and in particular in the chronicization process. Future studies are needed to better clarify if this finding is specific to cluster headache or if it represents an unspecific response to chronic pain.

  14. Ascending Projections from the Solitary Tract Nucleus to the Hypothalamus : A Phaseolus vulgaris Lectin Tracing Study in the Rat

    NARCIS (Netherlands)

    Horst, G.J. ter; de Boer, P.; Luiten, P.G.M.; Willigen, J.D. van

    1989-01-01

    The course of the ascending pathways originating from the anterior gustatory and posterior visceral sensory part of the solitary tract nucleus and the topographic organization of the projections to the hypothalamus in the rat were studied with anterogradely transported Phuseolus vulgaris lectin. In

  15. Atrazine alters expression of reproductive and stress genes in the developing hypothalamus of the snapping turtle, Chelydra serpentina.

    Science.gov (United States)

    Russart, Kathryn L G; Rhen, Turk

    2016-07-29

    Atrazine is an herbicide used to control broadleaf grasses and a suspected endocrine disrupting chemical. Snapping turtles lay eggs between late May and early June, which could lead to atrazine exposure via field runoff. Our goal was to determine whether a single exposure to 2ppb or 40ppb atrazine during embryogenesis could induce short- and long-term changes in gene expression within the hypothalamus of snapping turtles. We treated eggs with atrazine following sex determination and measured gene expression within the hypothalamus. We selected genes a priori for their role in the hypothalamus-pituitary-gonad or the hypothalamus-pituitary-adrenal axes of the endocrine system. We did not identify any changes in gene expression 24-h after treatment. However, at hatching AR, Kiss1R, and POMC expression was upregulated in both sexes, while expression of CYP19A1 and PDYN was increased in females. Six months after hatching, CYP19A1 and PRLH expression was increased in animals treated with 2ppb atrazine. Our study shows persistent changes in hypothalamic gene expression due to low-dose embryonic exposure to the herbicide atrazine with significant effects in both the HPG and HPA axes. Effects reported here appear to be conserved among vertebrates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

    Directory of Open Access Journals (Sweden)

    Vreugdenhil Erno

    2010-07-01

    Full Text Available Abstract Background This study compared the transduction efficiencies of an adeno-associated viral (AAV vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP, with a lentiviral (LV vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed, to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 108 or 1 × 109 genomic copies of AAV1-GFP and 1 × 105 transducing units of LV-dsRed. Results Immunostaining for GFP and dsRed showed that AAV1-GFP transduced significantly more cells than LV-dsRed in both the lateral hypothalamus and the amygdala. In addition, the number of LV particles that were injected can not easily be increased, while the number of AAV1 particles can be increased easily with a factor 100 to 1000. Both viral vectors appear to predominantly transduce neurons. Conclusions This study showed that AAV1 vectors are better tools to overexpress or knockdown genes in the lateral hypothalamus and amygdala of adult rats, since more cells can be transduced with AAV1 than with LV vectors and the titer of AAV1 vectors can easily be increased to transduce the area of interest.

  17. Energy balance affects luteinizing hormone pulses and expression of neurokinin B in the hypothalamus of ovariectomized gilts

    Science.gov (United States)

    The pubertal transition of gonadotropin secretion in pigs is metabolically gated, but the mechanisms that underpin this regulation are unknown. Kisspeptin and neurokinin B (NKB) are coexpressed in neurons within the arcuate nucleus of the hypothalamus (ARC) and are thought to play an important role ...

  18. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  19. The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer's Disease Patients.

    Science.gov (United States)

    Liu, Xiaozheng; Chen, Wei; Tu, Yunhai; Hou, Hongtao; Huang, Xiaoyan; Chen, Xingli; Guo, Zhongwei; Bai, Guanghui; Chen, Wei

    2018-01-01

    Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer's disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

  20. PPARg mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

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    Yang eLiu

    2015-09-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARg is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARg signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARg-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARg mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARg mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis, and the subfornical organ. Within the hypothalamus, PPARg was present at moderate levels in the suprachiasmatic nucleus and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARg was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARg mRNA expression was upregulated in the suprachiasmatic nucleus in response to fasting. Double in situ hybridization further demonstrated that PPARg was primarily expressed in neurons. Collectively, our observations provide a comprehensive map of PPARg distribution and regulation in the intact adult mouse hypothalamus.

  1. Differential contribution of CBP:CREB binding to corticotropin-releasing hormone expression in the infant and adult hypothalamus

    NARCIS (Netherlands)

    Cope, J.L.; Regev, L.; Chen, Y.; Korosi, A.; Rice, C.J.; Ji, S.; Rogge, G.A.; Wood, M.A.; Baram, T.Z.

    2014-01-01

    Corticotropin-releasing hormone (CRH) contributes crucially to the regulation of central and peripheral responses to stress. Because of the importance of a finely-tuned stress system, CRH expression is tightly regulated in an organ- and brain region-specific manner. Thus, in hypothalamus, CRH is

  2. Time-dependent effects of neuropeptide Y infusion in the paraventricular hypothalamus on ingestive and associated behaviors in rats

    NARCIS (Netherlands)

    van Dijk, G; Strubbe, JH

    In this study the role of neuropeptide Y (NPY) in the paraventricular nucleus of the hypothalamus (PVN) in the daily regulation of feeding, drinking, locomotor activity, and nestbox occupation was investigated. These behaviors were recorded during and after bilateral infusion of NPY into the PVN of

  3. Specific expression of an oxytocin-enhanced cyan fluorescent protein fusion transgene in the rat hypothalamus and posterior pituitary

    Czech Academy of Sciences Publication Activity Database

    Katoh, A.; Fujihara, H.; Ohbuchi, T.; Onaka, T.; Scott, W. S. III.; Dayanithi, Govindan; Yamasaki, Y.; Kawata, M.; Suzuki, H.; Otsubo, H.; Suzuki, Hi.; Murphy, D.; Ueta, Y.

    2010-01-01

    Roč. 204, č. 3 (2010), s. 275-285 ISSN 0022-0795 Institutional research plan: CEZ:AV0Z50390703 Keywords : magnocellular neurons * neurosecretory-cells * hypothalamus Subject RIV: FH - Neurology Impact factor: 3.099, year: 2010

  4. Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia.

    Science.gov (United States)

    Hunt, Nicholas J; Russell, Benjamin; Du, Man K; Waters, Karen A; Machaalani, Rita

    2016-06-01

    We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as compared with controls. Orexin maintains wakefulness/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (n = 7), air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of 7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles) (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin-positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin-positive neurons in the hypothalamus and fibre expression in the pons, and that IHH exposure does not prevent the nicotine-induced increase. Thus, although both nicotine and IHH are risk factors for SIDS, it appears they have opposing effects on OxA and OxB expression, with the IHH exposure closely mimicking what we recently found in SIDS. © 2016 Federation of European Neuroscience Societies and John

  5. Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    Full Text Available Ling Ma,1 Yong Jiang,2 Yanan Dong,2 Jun Gao,2 Bin Du,2 Dianwei Liu2 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Background: Subarachnoid hemorrhage (SAH can induce apoptosis in many regions of the brain including the cortex and hippocampus. However, few studies have focused on apoptosis in the hypothalamus after SAH. Although some antiapoptotic strategies have been developed for SAH, such as anti-tumor necrosis factor-alpha (TNF-α antibody, the molecular mechanisms underlying this condition have yet to be elucidated. Therefore, the purpose of this study was to evaluate whether SAH could induce apoptosis in the hypothalamus and identify the potential molecular mechanisms underlying the actions of anti-TNF-α antibody, as a therapeutic regimen, upon apoptosis. Materials and methods: SAH was induced in a rat model. Thirty minutes prior to SAH, anti-TNF-α antibody or U0126, an extracellular signal-regulated kinase (Erk inhibitor, was microinjected into the left lateral cerebral ventricle. In addition, phorbol-12-myristate-13-acetate was injected intraperitoneally immediately after the anti-TNF-α antibody microinjection. Then, real-time polymerase chain reaction, Western blotting and immunohistochemistry were used to detect the expression of caspase-3, bax, bcl-2, phosphorylated Erk (p-Erk and Erk. Finally, anxiety-like behavior was identified by using open field. Results: Levels of caspase-3, bax and bcl-2, all showed a temporary rise after SAH in the hypothalamus, indicating the induction of apoptosis in this brain region. Interestingly, we found that the microinjection of anti-TNF-α antibody could selectively block the elevated levels of bax, suggesting the potential role of anti-TNF-α antibody in the inhibition of SAH

  6. Effects of amino acids and vitamins on the ultrastructure of the hypothalamus and neurotransmitter in exhausted rats

    Directory of Open Access Journals (Sweden)

    Jian-wei CHEN

    2012-01-01

    Full Text Available Objective  To investigate the effects of amino acids and vitamins on the ultrastructure of the hypothalamus and neurotransmitter in exhausted rats. Methods  After adaptive swimming, 36 male SD rats were randomly divided into three groups, namely, capsule, control, and granules, with 12 rats in each group. Rats in 3 groups were given respectively amino acids capsule (8 kinds of essential amino acids and 11 kinds of vitamins were contained, normal drinking water, or amino acid-fructose beverage (2.5ml/100g, 2 times per day by gavage for 14 days. Exhaustion of rats was produced by non-loading swimming. The duration of the experiment lasted 14 days. After the last exhaustive swimming, the hypothalamus of the rats was removed for the observation of its ultrastructure under electron microscope. The contents of 5-hydroxytryptamine (5-HT, 5-hydroxyindole acetic acid (5HIAA, hydroxyphenyl acetic acid (HOPAC, and γ-aminobutyric acid (GABA in the hypothalamus were measured with high performance liquid chromatography (HPLC-ECD. Results  The mitochondrial structure in the brain cells of the capsule and granules groups were basically intact. On the other hand, the cells in the control group swelled and degenerated. Different degrees of swelling could be seen in the mitochondria. In addition, obvious morphological changes of the ultrastructure were observed under electron microscopy. Dissolution and rupture of the mitochondrial membrane and cristae were noted, even with the whole mitochondria disrupted and vacuolated. The contents of 5-HT, 5-HTAA, HOPAC, and GABA in the hypothalamus of rats in the capsule and the granules groups were significantly lower than those in the control group (PConclusion  Amino acids and vitamins compound can increase the resistance of the nerve center to fatigue by alleviating pathological changes of ultrastructure and changes in neurotransmitter levels of the hypothalamus.

  7. Autoradiographic localization of thyrotropin releasing hormone (TRH) receptors in the central nervous system

    International Nuclear Information System (INIS)

    Manaker, S.

    1985-01-01

    Quantitative autoradiography was used to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the rat and human central nervous system (CNS). The binding of [ 3 H]-3-methyl-histidine 2 -TRH ([ 3 H]-MeTRH) to TRH receptors was saturable, of a high affinity (K/sub d/ = 5 nM), and specific for TRH analogs. Studies with neurotoxins ibotenic acid and 6-hydroxydopamine (6-OHDA) suggest that TRH receptors within the amygdala are predominantly located on cell bodies, and not nerve terminals. Finally, an examination was made of the concentrations of TRH receptors in spinal cords of patients with amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons located in Lamina IX. Large decreases in TRH receptors were noted in ALS spinal cords, when compared to non-neurological controls, probably reflecting the loss of motor neurons. In addition, decreases in the TRH receptor concentration of Lamina II were observed. This finding may reflect the sensitivity of neurons throughout the CNS to the pathophysiologic mechanisms of neuronal degeneration which cause ALS

  8. Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug

    International Nuclear Information System (INIS)

    Saito, Y.; Price, R.W.; Rottenberg, D.A.; Fox, J.J.; Su, T.L.; Watanabe, K.A.; Philips, F.S.

    1982-01-01

    2'-Fluoro-5-methyl-1-ν-D-arabinosyluracil (FMAU) labeled with carbon-14 was used to image herpes simplex virus type 1-infected regions of rat brain by quantitative autoradiography. FMAU is a potent antiviral pyrimidine nucleoside which is selectively phosphorylated by virus-coded thymidine kinase. When the labeled FMAU was administered 6 hours before the rats were killed, the selective uptake and concentration of the drug and its metabolites by infected cells (defined by immunoperoxidase staining of viral antigens) allowed quantitative definition and mapping of HSV-1-infected structures in autoradiograms of brain sections. These results shown that quantitative autoradiography can be used to characterize the local metabolism of antiviral drugs by infected cells in vivo. They also suggest that the selective uptake of drugs that exploit viral thymidine kinase for their antiviral effect can, by appropriate labeling, be used in conjunction with clinical neuroimaging techniques to define infected regions of human brain, thereby providing a new approach to the diagnosis of herpes encephalitis in man

  9. Interactions of neurotoxins with non-NMDA glutamate receptors: an autoradiographic study

    International Nuclear Information System (INIS)

    Kuenig, G.; Niedermeyer, B.; Krause, F.; Hartmann, J.; Deckert, J.; Heinsen, H.; Beckmann, H.; Riederer, P.; Ransmayr, G.

    1994-01-01

    Neurotoxic substances are discussed to cause neurode-generation by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3 H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease. (author)

  10. Galanin-Expressing GABA Neurons in the Lateral Hypothalamus Modulate Food Reward and Noncompulsive Locomotion.

    Science.gov (United States)

    Qualls-Creekmore, Emily; Yu, Sangho; Francois, Marie; Hoang, John; Huesing, Clara; Bruce-Keller, Annadora; Burk, David; Berthoud, Hans-Rudolf; Morrison, Christopher D; Münzberg, Heike

    2017-06-21

    The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA GABA ), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHA GABA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA GABA neurons that coexpress the neuropeptide galanin (LHA Gal ). These LHA Gal neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHA Gal neurons may represent a subpopulation of LHA GABA neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHA Gal or LHA GABA neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differential VTA connectivity and transmitter release in these LHA neurons influences this behavior. LHA Gal or LHA GABA neuronal activation both increased operant food-seeking behavior, but only activation of LHA GABA neurons increased overall chow consumption. Additionally, LHA Gal or LHA GABA neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHA GABA neurons induced compulsive-like locomotor behavior; while LHA Gal neurons induced locomotor activity without compulsivity. Thus, LHA Gal neurons define a subpopulation of LHA GABA neurons without direct VTA innervation that mediate noncompulsive food-seeking behavior. We speculate that the striking difference in compulsive-like locomotor behavior is also based on differential VTA innervation. The downstream neural network responsible for this behavior and a potential role for galanin as neuromodulator remains to be identified. SIGNIFICANCE STATEMENT The lateral hypothalamus (LHA) regulates motivated feeding behavior via GABAergic LHA neurons. The molecular identity of LHA

  11. Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep Disturbances Induced by Early-Life Obesity.

    Science.gov (United States)

    Gazea, Mary; Patchev, Alexandre V; Anderzhanova, Elmira; Leidmaa, Este; Pissioti, Anna; Flachskamm, Cornelia; Almeida, Osborne F X; Kimura, Mayumi

    2018-01-10

    Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep-wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep-wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep-wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep. SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly influenced by dynamic reorganization of the brain during puberty. The present work shows that obesity during puberty leads to persistently dysregulated patterns of sleep and wakefulness by blunting serotonergic signaling in the lateral hypothalamus. It also shows that pharmacological mimicry of satiety with peptide YY 3-36 can reverse this neurochemical imbalance and

  12. Effect of Diffusion on the Autoradiographic Measurement of Macromolecular Synthesis in Specific Cell Types In Vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, K.; Schwarz, V. [Department of Chemical Pathology, University of Manchester, Manchester (United Kingdom)

    1970-02-15

    Organ slices cultured in vitro lack a capillary circulation. Cells within the slice are supplied with nutrients and oxygen by diffusion from the culture medium into the slice. The rate of synthesis of macromolecules, e.g. ribonucleic acid, deoxyribonucleic acid, protein or mucopolysaccharide can be determined in these circumstances by adding labelled precursors to the culture medium. Comparisons of the rate of synthesis between different types of cell within a single organ slice or between different slices can be quantitated by autoradiography and grain counting only if the concentration of labelled precursor in tissue water is uniform throughout all the slices. To achieve this aim the precursor should rapidly saturate the tissue water at the beginning of the incubation period, and subsequently diffusion into the slice should keep pace with consumption of the precursor by the cells. Experimental methods to measure the relevant parameters of any organ slice and precursor combination will be described. These parameters are the diffusion coefficient of the precursor in the organ slice, the rate of consumption of the precursor by each cell type, and the frequency and distribution of tissue within the slice. The relation between precursor concentration and position within the slice can be calculated under differing culture conditions, using the appropriate mathematical model. It is then possible to choose those conditions which give a uniform concentration of precursor throughout the organ slice. The methods are illustrated by consideration of ribonucleic acid synthesis from {sup 3}H-uridine in full thickness slices of human skin, an organ which contains several tissues including epidermis, hair follicle, eccrine sweat gland and sebaceous gland. (author)

  13. Inhibition of serotonin release by bombesin-like peptides in rat hypothalamus in vitro

    International Nuclear Information System (INIS)

    Saporito, M.S.; Warwick, R.O. Jr.

    1989-01-01

    We investigated the activity of bombesin (BN), neuromedin-C (NM-C) and neuromedin-B (NM-B) on serotonin (5-HT) release and reuptake in rat hypothalamus (HYP) in vitro. BN and NM-C but not NM-B decreased K + evoked 3 H-5-HT release from superfused HYP slices by 25%. Bacitracin, a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K + evoked 3 H-5-HT release. Phosphoramidon (PAN, 10 μM) an endopeptidase 24.11 inhibitor, abolished the inhibitory effect of BN, but not NM-C, on K + evoked 3 H-5-HT release. The peptidyl dipeptidase A inhibitor enalaprilat (ENP, 10 μM), enhanced both BN and NM-C inhibition of 3 H-5-HT release. Bestatin (BST, 10 μM) had no effect on BN or NM-C inhibitory activity on 3 H-5-HT release. Neither BN, NM-C nor NM-B affected reuptake of 3 H-5-HT into HYP synaptosomes alone or in combination with any of the peptidase inhibitors, nor did these peptides alter the ability of fluoxetine to inhibit 3 H-5-HT uptake

  14. Effects of estradiol on norepinephrine and prostaglandin efflux in medial basal hypothalamus of ovariectomized rats

    International Nuclear Information System (INIS)

    Cardinali, D.P.; Fernandez Pardal, J.; Gimeno, M.F.; Gimeno, A.L.

    1982-01-01

    The spontaneous and K + -stimulated efflux of norepinephrine (NE) and the release of PGE 2 and PGF 2 α were examined in medial basal hypothalamus (MBH) of ovariectomized rats killed before and during the LH release that follows estradiol treatment. As compared to vehicle-treated, ovariectomized rats, estradiol-primed rats exhibited a 60% more increase in K + -stimulated 3 H-overflow of MBH slices preloaded with 3 H-NE at morning hours (1000 hours). Estradiol treatment did not result in further increase of K + -induced 3 H release from MBH slices at the time of LH release (1700 hours), nor affected labelled NE release in occipital cortex slices. A significant difference between K + -stimulated NE release of vehicle-treated spayed rats killed at 1000 and 1700 hours was observed, the latter showing 54% more release upon stimulus. PGE 2 efflux was time-dependent being highest at the evening in both vehicle- and estradiol-treated animals. The MBH of estrogenized rats released significantly more PGE 2 at the evening as compared to the controls. The release of PGF 2 α remained essentially unchanged regardless of estradiol treatment or time of day. The present results offer additional support to the involvement of MBH catecholamines and prostaglandins in the mechanism of LH secretion in the rat. (author)

  15. Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    Full Text Available The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC, plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT-expressing neurons in the ARC. Gene expression patterns are remarkably distinct in each individual cholinergic neuron. Two-thirds of cholinergic neurons express tyrosine hydroxylase (Th mRNA. A large subset of these Th-positive cholinergic neurons is GABAergic as they express the GABA synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter transcripts. Some cholinergic neurons also express the vesicular glutamate transporter transcript gene. POMC and POMC-processing enzyme transcripts are found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene expression patterns in individual cholinergic cells appear to be highly regulated in a cell-specific manner. In fact, membrane receptor transcripts are clustered with their respective intracellular signaling and downstream targets. This novel population of cholinergic neurons may be part of the neural circuitries that detect homeostatic need for food and control the drive to eat.

  16. Effect of parenteral glutamate treatment on the localization of neurotransmitters in the mediobasal hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I; Fonnum, F

    1978-01-01

    The localization of cholinergic, aminergic and amino acid-ergic neurones in the mediobasal hypothalamus has been studied in normal rat brain and in brains where neurones in nucleus arcuatus were destroyed by repeated administration of 2 mg/g body weight monosodium glutamate to newborn animals. In normal animals acetylcholinesterase staining, choline acetyltransferase and aromatic L-amino acid decarboxylase were concentrated in the median eminence and the arcuate nucleus. Glutamate decarboxylase was concentrated at the boundary between the ventromedial and the arcuate nuclei, with lower activity in the arcuate nucleus and very low activity in the median eminence. Nucleus arcuatus contained an intermediate level of high affinity glutamate uptake. In the lesioned animals, there were significant decreases in choline acetyltransferase, acetylcholinesterase staining and glutamate decarboxylase in the median eminence, whereas choline acetyltransferase activity and acetylcholinesterase staining, but not glutamate decarboxylase activity, were decreased in nucleus arcuatus. Aromatic L-amino acid decarboxylase was unchanged in all regions studied. The high affinity uptakes of glutamate, dopamine and noradrenaline, and the endogenous amino acid levels were also unchanged in the treated animals. The results indicate the existence of acetylcholine- and GABA-containing elements in the tuberoinfundibular tract. They further indicate that the dopamine cells in the arcuate nucleus are less sensitive to the toxic effect of glutamate than other cell types, possibly because they contain less glutamate receptors.

  17. α/β-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility

    Directory of Open Access Journals (Sweden)

    Alexandre Fisette

    2016-10-01

    Full Text Available α/β-Hydrolase domain 6 (ABHD6 is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG. Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMHKO have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMHKO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet. Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility.

  18. Self-administration of morphine into the lateral hypothalamus in the mouse.

    Science.gov (United States)

    Cazala, P; Darracq, C; Saint-Marc, M

    1987-07-28

    BALB/c mice were chronically and unilaterally implanted with a guide cannula, the tip of which was positioned 1 mm above the lateral hypothalamus (LH). On each experimental day, a stainless-steel injection cannula was inserted into the LH, and self-administration of morphine or vehicle in this brain area was studied by using a spatial discrimination test in a Y-maze. In a first experiment, we observed that when mice had access to morphine (0.1 microgram by injection) they rapidly discriminated the reinforced arm from the neutral arm of the maze in order to self administer, with increasing frequency, the drug into the LH. In contrast when only vehicle was present, the two arms were no longer discriminated. In a second experiment we compared the effects of 3 doses of morphine (0.1 microgram, 0.05 microgram and 0.025 microgram by injection); optimal discrimination was obtained with the lowest dose used. In a third experiment we observed that subcutaneous injections of naloxone (4 mg/kg) progressively reduced the number of self-administrations of morphine into the LH, a result which suggests that this response is dependent on an opiate receptor mechanism.

  19. Lateral hypothalamus contains two types of palatability-related taste responses with distinct dynamics.

    Science.gov (United States)

    Li, Jennifer X; Yoshida, Takashi; Monk, Kevin J; Katz, Donald B

    2013-05-29

    The taste of foods, in particular the palatability of these tastes, exerts a powerful influence on our feeding choices. Although the lateral hypothalamus (LH) has long been known to regulate feeding behavior, taste processing in LH remains relatively understudied. Here, we examined single-unit LH responses in rats subjected to a battery of taste stimuli that differed in both chemical composition and palatability. Like neurons in cortex and amygdala, LH neurons produced a brief epoch of nonspecific responses followed by a protracted period of taste-specific firing. Unlike in cortex, however, where palatability-related information only appears 500 ms after the onset of taste-specific firing, taste specificity in LH was dominated by palatability-related firing, consistent with LH's role as a feeding center. Upon closer inspection, taste-specific LH neurons fell reliably into one of two subtypes: the first type showed a reliable affinity for palatable tastes, low spontaneous firing rates, phasic responses, and relatively narrow tuning; the second type showed strongest modulation to aversive tastes, high spontaneous firing rates, protracted responses, and broader tuning. Although neurons producing both types of responses were found within the same regions of LH, cross-correlation analyses suggest that they may participate in distinct functional networks. Our data shed light on the implementation of palatability processing both within LH and throughout the taste circuit, and may ultimately have implications for LH's role in the formation and maintenance of taste preferences and aversions.

  20. Macronutrients and the FTO gene expression in hypothalamus; a systematic review of experimental studies.

    Science.gov (United States)

    Doaei, Saeid; Kalantari, Naser; Mohammadi, Nastaran Keshavarz; Tabesh, Ghasem Azizi; Gholamalizadeh, Maryam

    The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions. Copyright © 2017. Published by Elsevier B.V.

  1. Leptin and glucocorticoid signaling pathways in the hypothalamus of female and male fructose-fed rats

    Directory of Open Access Journals (Sweden)

    Vojnović-Milutinović Danijela

    2014-01-01

    Full Text Available Alterations in leptin and glucocorticoid signaling pathways in the hypothalamus of male and female rats subjected to a fructose-enriched diet were studied. The level of expression of the key components of the leptin signaling pathway (neuropeptide Y /NPY/ and suppressor of cytokine signaling 3 /SOCS3/, and the glucocorticoid signaling pathway (glucocorticoid receptor /GR/, 11β-hydroxysteroid dehydrogenase type 1 /11βHSD1/ and hexose-6-phosphate dehydrogenase /H6PDH/ did not differ between fructose-fed rats and control animals of both genders. However, in females, a fructose-enriched diet provoked increases in the adiposity index, plasma leptin and triglyceride concentrations, and displayed a tendency to decrease the leptin receptor (ObRb protein and mRNA levels. In male rats, the fructose diet caused elevations in plasma non-esterified fatty acids and triglycerides, as well as in both plasma and hypothalamic leptin concentrations. Our results suggest that a fructose-enriched diet can induce hyperleptinemia in both female and male rats, but with a more pronounced effect on hypothalamic leptin sensitivity in females, probably contributing to the observed development of visceral adiposity. [Projekat Ministarstva nauke Republike Srbije, br. III41009

  2. Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish

    Science.gov (United States)

    Nesan, Dinushan; Vijayan, Mathilakath M.

    2016-01-01

    In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish. PMID:26940285

  3. A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary.

    Science.gov (United States)

    Whirledge, Shannon; Cidlowski, John A

    2013-12-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success.

  4. Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation

    DEFF Research Database (Denmark)

    Dragano, Nathalia R V; Solon, Carina; Ramalho, Albina F

    2017-01-01

    BACKGROUND: The consumption of large amounts of dietary fats is one of the most important environmental factors contributing to the development of obesity and metabolic disorders. GPR120 and GPR40 are polyunsaturated fatty acid receptors that exert a number of systemic effects that are beneficial...... for metabolic and inflammatory diseases. Here, we evaluate the expression and potential role of hypothalamic GPR120 and GPR40 as targets for the treatment of obesity. METHODS: Male Swiss (6-weeks old), were fed with a high fat diet (HFD, 60% of kcal from fat) for 4 weeks. Next, mice underwent stereotaxic...... the treatment period. At the end of the experiment, the hypothalamus was collected for real-time PCR analysis. RESULTS: We show that both receptors are expressed in the hypothalamus; GPR120 is primarily present in microglia, whereas GPR40 is expressed in neurons. Upon intracerebroventricular treatment, GW9508...

  5. [Role of estrogen-sensitive neurons in the arcuate region of the hypothalamus in the mechanism of luteinizing hormone release].

    Science.gov (United States)

    Babichev, V N; Ignatkov, V Ia

    1978-01-01

    Experiments were conducted on rats; estradiol brought to the arcuate region of the hypothalamus by means of microionophoresis led to the increase of the region of the hypothalamus by means of microionophoresis led to the increase of the blood luteinizing hormone (LH) level during the following stages of the estral cycle-diestrus 1, diestrus 2, and the first half day of the proestrus; as to the second half of the proestrus day--estradiol decreased its level. Changes in the LH level in the hypophysis under the influence of the microionophoretic introduction of estradiol into the arcuate region occurred during the second half of the day of diestrus 2 (reduction), and during the estrus (elevation). In the majority of cases a rise of the blood level was combined with the neuron activation in the arcuate region under the influence of estradiol.

  6. A very large number of GABAergic neurons are activated in the tuberal hypothalamus during paradoxical (REM sleep hypersomnia.

    Directory of Open Access Journals (Sweden)

    Emilie Sapin

    Full Text Available We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD(67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD(67in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD(+, Fos-ir/MCH(+, and GAD(+/MCH(+ double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD(+ neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.

  7. Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data.

    Science.gov (United States)

    Pedroso, Amanda P; Souza, Adriana P; Dornellas, Ana P S; Oyama, Lila M; Nascimento, Cláudia M O; Santos, Gianni M S; Rosa, José C; Bertolla, Ricardo P; Klawitter, Jelena; Christians, Uwe; Tashima, Alexandre K; Ribeiro, Eliane B

    2017-04-07

    Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.

  8. Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I; Fonnum, F

    1980-01-01

    The effects of bilateral transection of the fornix bundle on the high affinity uptake of glutamate and on the amino acid content in several nuclei of rat forebrain and hypothalamus were studied in order to investigate the possible role of glutamate as a transmitter of these fibres. This lesion decreased the high affinity uptake of L-glutamate by 60 to 70% in the mammillary body and lateral septum, and by 40 to 50% in the anterior diagonal band nucleus, the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the nucleus accumbens. The content of endogenous glutamate in samples dissected from freeze-dried tissue also decreased significantly in these regions. Endogenous aspartate was slightly decreased in the anterior diagonal band nucleus and the mammillary body, but unchanged in the other regions. No significant changes were seen in the levels of serine, ..gamma..-aminobutyric acid, glutamine and taurine, except for an increase in glutamine and taurine in the bed nucleus of the stria terminalis. The high affinity uptake of ..gamma..-aminobutyric acid, tested in the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the mammillary body, was unchanged after the lesion. The results indicate that allocortical efferents innervating subcortial nuclei through the fornix might use glutamate as a transmitter. The study further supports the concept that glutamate plays an important role as transmitter of several different corticofugal fibre systems in mammalian brain.

  9. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  10. Macro-and micro-autoradiographic study in comparison with the incorporation of 35S-methionine by various tissue protein in organism

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Mei Shengping; Le Shangcheng

    1990-12-01

    The purpose of the study was to observe the incorporation level of 35 S-methionine by various tissue protein in organism. By the use of the macro-and micro-autoradiographic technique, the incorporation of 35 S-methionine by the tissues has been utilized as an index of various tissue protein synthesis. On this basis, the further experiments showed that tracer agent 35 S-methionine was dominantly incorporated in the immature cells of bone marrow and the tissue of liver, kidney and spleen. Its incorporation increased gradually with time. From the experimental results it can be concluded that a strong protein biosynthesis metabolism was produced in these tissues. While the tissues have important physiological function in organism, such as heart, lung and skeletal muscle, but the protein biosynthesis in those tissues was at a low level

  11. Autoradiographic visualization of A 1-adenosine receptors in brain and peripheral tissues of rat and guinea pig using 125I-HPIA

    International Nuclear Information System (INIS)

    Weber, R.G.; Lohse, M.J.; Jones, C.R.; Palacios, J.M.

    1988-01-01

    A 1 -adenosine receptors were identified in sections of rat brain and guinea pig kidney with the radioiodinated agonist 1 25I-N 6 -p-hydroxyphenylisopropyladenosine ( 1 25I-HPIA) using in vitro autoradiography. The affinities of adenosine receptor ligands in competing with 1 25I-HPIA binding to tissue sections were in good agreement with those found in membranes and indicate that the binding site represents an A 1 pattern of [ 3 H]N 6 -cyclohexyladenosine ([ 3 H]CHA) binding sites determined previously, with highest densities in the hippocampus and dentate gyrus, the cerebellar cortex, some thalamic nuclei and certain layers of the cerebral cortex. In the guinea pig kidney 1 25I-HPIA labelled longitudinal structures in the medulla. This study demonstrates that 1 25I-HPIA allows the autoradiographic detection of A-1 adenosine receptors in the brain and peripheral organs and has the advantage of short exposure times (author)

  12. Autoradiographical in-vitro examination of the cell proliferation of persisting psoriatic plaques in preferred areas under therapy with ultraviolet light: Photochemotherapy (PUVA) and selective ultraviolet phototherapy (SUP)

    International Nuclear Information System (INIS)

    Middendorf, M.

    1982-01-01

    The application of ultraviolet rays (PUVA, SUP) brought significant progress in the treatment of psoriasis. The goal of UV-irradiation is to normalise the epidermal growth conditions. The cell cycle of persisting psoriatic plaque in preferred areas was examined under therapy with PUVA and SUP using an autoradiographic in-vitro method, double labelling with 14 C- and 3 H-thymididin. The results were compared to the known cell-kinetic parameters of psoriasis. The values thus obtained confirm the characteristic changes in the cell cycle of psoriasis. Furthermore, there is a block within the DNA-synthesis phase in the plaques persisting under UV-therapy. The resistence of persisting psoriatic plaques in preferred regions against UV-therapy is regarded as an indication of an extreme disturbance in the proliferation behaviour of the psoriatic skin. (orig./MG) [de

  13. A two emulsion autoradiographic technique and the discriminating of the three different types of labelling after double labelling with 3H- and 14C-thymidine

    International Nuclear Information System (INIS)

    Schultze, B.; Maurer, W.; Hagenbusch, H.

    1976-01-01

    The first part of the paper deals with a two emulsion autoradiographic technique for double labelling experiments with 3 H- and 14 C-thymidine which permits a clear discrimination of the different types of labelling. In the second part the application of this technique to cell kinetics studies is discussed. Accurate discrimination between the different types of labelling, namely purely 3 H-, purely 14 C- and double ( 3 H + 14 C) labelling, is only possible if the activity ratio of 3 H- to 14 C-thymidine is sufficiently high. This condition is necessary for a reliable distinction between those grains in the first emulsion which are due to true 3 H-labelling and spurious grains which are simultaneously produced in the same emulsion by 14 C-β- particles. Experiments are described to determine the required activity ratio of 3 H- to 14 C-thymidine. (author)

  14. The application of data derived from autoradiographic studies with 241Pu in the formulation of a bone dosimetric model for 239Pu

    International Nuclear Information System (INIS)

    Priest, N.D.; Hunt, B.W.

    1979-01-01

    Recently a dosimetric model for 239 Pu in bone has been published which in conjunction with the general ICRP dosimetric model for actinides is used to calculate annual limits of intake for 239 Pu. This model allows for the burial of plutonium in bone, for the recycling of plutonium within the skeleton and for the retention of plutonium in the bone marrow. The model was based upon published descriptions of the distribution and redistribution patterns of plutonium in bone and on evidence obtained from autoradiographic studies of bone from animals injected with 241 Pu. The experiments with 241 Pu demonstrated the initial uptake of plutonium by bone surfaces. As a result of the growth and drift processes much of this plutonium became either buried in the bone or was retained within macrophages in the bone marrow. (author)

  15. Kinetics of Human Haematopoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Cronkite, E. P. [Forschungsgruppe Freiburg, Institut fuer Haematologie der Gesellschaft fuer Strahlenforschung Assoziation mit EURATOM, Freiburg/Breisgau, Federal Republic of Germany (Germany); Medical Research Center, Brookhaven National Laboratory, Upton, Long Island, NY (United States)

    1967-07-15

    An understanding of the parameters of normal cell proliferation is a prerequisite for the understanding of the disturbances induced by radiation. The disturbances induced by radiation on cell renewal systems has been presented in detail by Bond, Fliedner and Archambeau. In this paper a method of studying the concepts and actual observations on human haemopoiesis will be summarized. Details of the procedures, methods and concepts are published. The method employed is the serial.autoradiographic study of haemopoietic tissues after labelling the DNA of proliferating compartments by intravenous injection of tritiated thymidine (3HTDR) a specific DNA precursor. One can then observe the flow of labelled cells through mitosis, the transit of labelled cells from a proliferating compartment to a non proliferating compartment and the migration of cells from tissues to blood.

  16. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    Science.gov (United States)

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive.

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    Campbell, Erin J; Mitchell, Caitlin S; Adams, Cameron D; Yeoh, Jiann Wei; Hodgson, Deborah M; Graham, Brett A; Dayas, Christopher V

    2017-10-01

    Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3 h on postnatal days 2-14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5 mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Arcuate nucleus of hypothalamus is involved in mediating the satiety effect of electroacupuncture in obese rats.

    Science.gov (United States)

    Fei Wang; Tian, De Run; Tso, Patrick; Han, Ji Sheng

    2011-12-01

    Obesity is a major health problem in the world. Since effective remedies are rare, researchers are trying to discover new therapies for obesity, and acupuncture is among the most popular alternative approaches. This study investigated the anti-obesity mechanisms of EA, using a rat model of diet-induced obesity. After feeding with a high-fat diet for 9 weeks, a number of rats who gained weight that surpassed the maximal body weight of rats in the chow-fed group were considered obese and employed in the study. A 2 Hz EA treatment at the acupoints ST36/SP6 with the intensity increasing stepwise from 0.5-1-1.5 mA was given once a day for 30 min. Rats treated with EA showed significantly decreased food intake and reduced body weight compared with the rats in DIO and restraint group. EA treatment increased peptide levels of α-MSH and mRNA levels of its precursor POMC in the arcuate nuclear of hypothalamus (ARH) neurons. In addition, the cerebral spinal fluid (CSF) content of α-MSH was elevated by EA application. ARH lesions by monosodium glutamate abolished the inhibition effect of EA on food intake and body weight. A non-acupoint stimulation did not show the benefit effect on food intake inhibition and body weight reduction compared with restraint and ST36/SP6 EA treatment. We concluded that EA treatment at ST36/SP6 acted through ARH to significantly inhibit food intake and body weight gain when fed a high-fat diet and that the stimulation of α-MSH expression and release might be involved in the mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Identification of transcripts related to high egg production in the chicken hypothalamus and pituitary gland.

    Science.gov (United States)

    Shiue, Yow-Ling; Chen, Lih-Ren; Chen, Chih-Feng; Chen, Yi-Ling; Ju, Jhy-Phen; Chao, Ching-Hsien; Lin, Yuan-Ping; Kuo, Yu-Ming; Tang, Pin-Chi; Lee, Yen-Pai

    2006-09-15

    To identify transcripts related to high egg production expressed specifically in the hypothalamus and pituitary gland of the chicken, two subtracted cDNA libraries were constructed. Two divergently selected strains of Taiwan Country Chickens (TCCs), B (sire line) and L2 (dam line) were used; they had originated from a single population and were further subjected (since 1982) to selection for egg production to 40 wk of age and body weight/comb size, respectively. A total of 324 and 370 clones were identified from the L2-B (L2-subtract-B) and the B-L2 subtracted cDNA libraries, respectively. After sequencing and annotation, 175 and 136 transcripts that represented 53 known and 65 unknown non-redundant sequences were characterized in the L2-B subtracted cDNA library. Quantitative reverse-transcription (RT)-PCR was used to screen the mRNA expression levels of 32 randomly selected transcripts in another 78 laying hens from five different strains. These strains included the two original strains (B and L2) used to construct the subtracted cDNA libraries and an additional three commercial strains, i.e., Black- and Red-feather TCCs and Single-Comb White Leghorn (WL) layer. The mRNA expression levels of 16 transcripts were significantly higher in the L2 than in the B strain, whereas the mRNA expression levels of nine transcripts, BDH, NCAM1, PCDHA@, PGDS, PLAG1, PRL, SAR1A, SCG2 and STMN2, were significantly higher in two high egg production strains, L2 and Single-Comb WL; this indicated their usefulness as molecular markers of high egg production.

  20. Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus.

    Science.gov (United States)

    Lee, Hyosang; Kim, Dong-Wook; Remedios, Ryan; Anthony, Todd E; Chang, Angela; Madisen, Linda; Zeng, Hongkui; Anderson, David J

    2014-05-29

    Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1(+) (but not Esr1(-)) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1(+) neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1(+) neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population.

  1. Contributions of HIV infection in the hypothalamus and substance abuse/use to HPT dysregulation

    Science.gov (United States)

    Langford, Dianne; Baron, David; Joy, Javed; Valle, Luis Del; Shack, Jonathon

    2010-01-01

    Over the last two decades, consequences of HIV infection of the CNS on disease severity and clinical neuropsychiatric manifestations have changed. These changes are due, in part, to improved control of peripheral infection by new anti-retroviral medications and more efficient CNS penetration of combination anti-retroviral therapies (cART). While the life spans of HIV-infected patients have been prolonged with successful cART, the spectrum of cognitive alterations observed in these patients has broadened. Recent studies report that there does not appear to be a single prototypical pattern of neuropsychological impairment associated with HIV, but rather it includes diverse manifestations. Some co-morbidities such as substance abuse or depression, likely play significant roles in the neuropsychiatric profiles of some HIV-infected patients. Newly recognized factors contributing to neurocognitive impairments include ageing and unanticipated side effects from cART. Likewise, disturbances in neuroendocrine functioning are emerging as potentially important contributors to HIV-associated neurocognitive alterations. A retrospective review of clinical data from a small cohort of HIV-infected patients admitted to the psychiatric unit of an inner city hospital indicates that thyroid stimulating hormone levels were abnormal in 27% of the patients. Our data from analyses of post-mortem tissues from HIV patients show for the first time HIV infection of the hypothalamus and altered levels of thyroid hormone processing enzymes. Decreased vasopressin and oxytocin immunoreactivity in hypothalamic neurons was also observed. Thus, HIV infection of the CNS may contribute to changes in hypothalamic hormone signaling, thereby resulting in abnormal hypothalamic-pituitary-thyroid axis feedback and neuropsychiatric dysfunction. PMID:21115295

  2. Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis.

    Science.gov (United States)

    Stagi, Stefano; di Tommaso, Mariarosaria; Scalini, Perla; Lapi, Elisabetta; Losi, Stefania; Bencini, Erica; Masoni, Fabrizio; Dosa, Laura; Becciani, Sabrina; de Martino, Maurizio

    2016-06-01

    To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. Cross-sectional study with retrospective analysis. University pediatric hospital. Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years). None. We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus

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    Guilding Clare

    2009-08-01

    Full Text Available Abstract Background In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many brain areas, including those implicated in the regulation of appetite and feeding. The recent development of mice in which clock gene/protein activity is reported by bioluminescent constructs (luciferase or luc now enables us to track molecular oscillations in numerous tissues ex vivo. Consequently we determined both clock activities and responsiveness to metabolic perturbations of cells and tissues within the mediobasal hypothalamus (MBH, a site pivotal for optimal internal homeostatic regulation. Results Here we demonstrate endogenous circadian rhythms of PER2::LUC expression in discrete subdivisions of the arcuate (Arc and dorsomedial nuclei (DMH. Rhythms resolved to single cells did not maintain long-term synchrony with one-another, leading to a damping of oscillations at both cell and tissue levels. Complementary electrophysiology recordings revealed rhythms in neuronal activity in the Arc and DMH. Further, PER2::LUC rhythms were detected in the ependymal layer of the third ventricle and in the median eminence/pars tuberalis (ME/PT. A high-fat diet had no effect on the molecular oscillations in the MBH, whereas food deprivation resulted in an altered phase in the ME/PT. Conclusion Our results provide the first single cell resolution of endogenous circadian rhythms in clock gene expression in any intact tissue outside the SCN, reveal the cellular basis for tissue level damping in extra-SCN oscillators and demonstrate that an oscillator in the ME/PT is responsive to changes in metabolism.

  4. Connectivity from OR37 expressing olfactory sensory neurons to distinct cell types in the hypothalamus

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    Andrea eBader

    2012-11-01

    Full Text Available Olfactory sensory neurons which express a member from the OR37 subfamily of odorant receptor genes are wired to the main olfactory bulb in a unique monoglomerular fashion; from these glomeruli an untypical connectivity into higher brain centers exists. In the present study we have investigated by DiI and transsynaptic tracing approaches how the connection pattern from these glomeruli into distinct hypothalamic nuclei is organized. The application of DiI onto the ventral domain of the bulb which harbors the OR37 glomeruli resulted in the labeling of fibers within the paraventricular and supraoptic nucleus of the hypothalamus; some of these fibers were covered with varicose-like structures. No DiI-labeled cell somata were detectable in these nuclei. The data indicate that projection neurons which originate in the OR37 region of the main olfactory bulb form direct connections into these nuclei. The cells that were labeled by the transsynaptic tracer WGA in these nuclei were further characterized. Their distribution pattern in the paraventricular nucleus was reminiscent of cells which produce distinct neuropeptides. Double labeling experiments confirmed that they contained vasopressin, but not the related neuropeptide oxytocin. Morphological analysis revealed that they comprise of magno- and parvocellular cells. A comparative investigation of the WGA-positive cells in the supraoptic nucleus demonstrated that these were vasopressin-positive, as well, whereas oxytocin-producing cells of this nucleus also contained no transsynaptic tracer. Together, the data demonstrate a connectivity from OR37 expressing sensory neurons to distinct hypothalamic neurons with the same neuropeptide content.

  5. Neurotensin releases norepinephrine differentially from perfused hypothalamus of sated and fasted rat

    International Nuclear Information System (INIS)

    Lee, T.F.; Rezvani, A.H.; Hepler, J.R.; Myers, R.D.

    1987-01-01

    The central injection of neurotensin (NT) has been reported to attenuate the intake of food in the fasted animal. To determine whether endogenous norepinephrine (NE) is involved in the satiating effect of NT, the in vivo activity of NE in circumscribed sites in the hypothalamus of the unanesthetized rat was examined. Bilateral guide tubes for push-pull perfusion were implanted stereotaxically to rest permanently above one of several intended sites of perfusion, which included the paraventricular nucleus (PVN), ventromedial nucleus (VMN), and the lateral hypothalamic (LH) area. After endogenous stores of NE at a specific hypothalamic locus were radiolabeled by microinjection of 0.02-0.5 μCi of [ 3 H]NE, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 μl/min over successive intervals of 5.0 min. When 0.05 or 0.1 μg/μl NT was added to the perfusate, the peptide served either to enhance or educe the local release of NE at 50% of the sites of perfusion. In these experiments, the circumscribed effect of NT on the characteristics of catecholamine efflux depended entirely on the state of hunger or satiety of the rat. That is, when NT was perfused in the fully satiated rat, NE release was augmented within the PVn or VMN; conversely, NE release was inhibited in the LH. in the animal fasted for 18-22 h, NT exerted an opposite effect on the activity of NE within the same anatomical loci in that the efflux of NE was enhanced in the LH but attenuated or unaffected in the PVN or VMN. Taken together, these observations provide experimental support for the view-point that NT could act as a neuromodulator of the activity of hypothalamic noradrenergic neurons that are thought to play a functional role in the regulation of food intake

  6. The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder.

    Science.gov (United States)

    Martín-Blanco, Ana; Ferrer, Marc; Soler, Joaquim; Arranz, Maria Jesús; Vega, Daniel; Calvo, Natalia; Elices, Matilde; Sanchez-Mora, Cristina; García-Martinez, Iris; Salazar, Juliana; Carmona, Cristina; Bauzà, Joana; Prat, Mónica; Pérez, Víctor; Pascual, Juan C

    2016-06-01

    Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

  7. Hubs and spokes of the lateral hypothalamus: cell types, circuits and behaviour

    Science.gov (United States)

    Bonnavion, Patricia; Mickelsen, Laura E.; Fujita, Akie; de Lecea, Luis

    2016-01-01

    Abstract The hypothalamus is among the most phylogenetically conserved regions in the vertebrate brain, reflecting its critical role in maintaining physiological and behavioural homeostasis. By integrating signals arising from both the brain and periphery, it governs a litany of behaviourally important functions essential for survival. In particular, the lateral hypothalamic area (LHA) is central to the orchestration of sleep–wake states, feeding, energy balance and motivated behaviour. Underlying these diverse functions is a heterogeneous assembly of cell populations typically defined by neurochemical markers, such as the well‐described neuropeptides hypocretin/orexin and melanin‐concentrating hormone. However, anatomical and functional evidence suggests a rich diversity of other cell populations with complex neurochemical profiles that include neuropeptides, receptors and components of fast neurotransmission. Collectively, the LHA acts as a hub for the integration of diverse central and peripheral signals and, through complex local and long‐range output circuits, coordinates adaptive behavioural responses to the environment. Despite tremendous progress in our understanding of the LHA, defining the identity of functionally discrete LHA cell types, and their roles in driving complex behaviour, remain significant challenges in the field. In this review, we discuss advances in our understanding of the neurochemical and cellular heterogeneity of LHA neurons and the recent application of powerful new techniques, such as opto‐ and chemogenetics, in defining the role of LHA circuits in feeding, reward, arousal and stress. From pioneering work to recent developments, we review how the interrogation of LHA cells and circuits is contributing to a mechanistic understanding of how the LHA coordinates complex behaviour. PMID:27302606

  8. Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats.

    Science.gov (United States)

    Renzi, A; De Luca, L A; Menani, J V

    2002-09-15

    In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

  9. Lateral Hypothalamus as a Motivation-Cognition Interface in the Control of Feeding Behavior

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    Gorica D. Petrovich

    2018-04-01

    Full Text Available Converging evidence for an essential function of the lateral hypothalamus (LHA in the control of feeding behavior has been accumulating since the classic work conducted almost 80 years ago. The LHA is also important in reward and reinforcement processes and behavioral state control. A unifying function for the LHA across these processes has not been fully established. Nonetheless, it is considered to integrate motivation with behavior. More recent work has demonstrated that the LHA is also required when cognitive processes, such as associative learning and memory control feeding behavior, suggesting it may serve as a motivation-cognition interface. Structurally, the LHA is well positioned within the cerebral hemisphere, with its extensive connectional network across the forebrain-brainstem axis, to link motivational and behavioral systems with cognitive processes. Studies that examined how learned cues control food seeking and consumption have implicated the LHA, but due to methodological limitations could not determine whether it underlies motivation, learning, or the integration of these processes. Furthermore, the identification of specific substrates has been limited by the LHA’s extraordinary complexity and heterogeneity. Recent methodological advancements with chemo-and opto-genetic approaches have enabled unprecedented specificity in interrogations of distinct neurons and their pathways in behaving animals, including manipulations during temporally distinct events. These approaches have revealed novel insights about the LHA structure and function. Recent findings that the GABA LHA neurons control feeding and food-reward learning and memory will be reviewed together with past work within the context of the LHA function as an interface between cognition and motivation.

  10. Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus.

    Science.gov (United States)

    Nguyen, Long The; Saad, Sonia; Tan, Yi; Pollock, Carol; Chen, Hui

    2017-07-01

    Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity. © 2017 Society for Endocrinology.

  11. Colloid cyst of the third ventricle, hypothalamus, and heart: a dangerous link for sudden death

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    Turillazzi Emanuela

    2012-10-01

    Full Text Available Abstract Colloid cysts are rare congenital, intracranial neoplasms, commonly located in the third ventricle. Colloid cysts are endodermal congenital malformations. The cysts commonly range in size from 1–2 cm in diameter, although large cysts >3 cm in size have been reported. The components of the cyst include an outer fibrous capsule over an inner epithelium. The epithelium is usually a single layer of mucin-producing or ciliated cells. Such cysts contain mucoid and gelatinous material, which is positive for both Periodic acid Schiff (PAS and mucicarmen staining. Although colloid cysts usually represent histopathologically benign neoplasms, they can result in sudden, unexpected and potentially lethal complications. The mechanism(s of death is still a controversial subject and several mechanisms have been postulated to explain the sudden onset of severe symptoms and of fatal rapid deterioration in patients with colloid cysts. In this case, macroscopic and histological findings addressed the diagnosis of colloid cyst of the third ventricle with diffuse myocardial injury (coagulative myocytolysis or contraction band necrosis, CBN and led us to conclude that acute cardiac arrest due to hypothalamus stimulation in the context of colloid cyst of the third ventricle was the cause of death. As the hypothalamic structures which are involved in neuroendocrine and autonomic regulation playing a key role in cardiovascular control are located close to the walls of the third ventricle which is the most frequent anatomical site of colloid cyst, this may suggest that reflex cardiac effects due to the compression of the hypothalamic cardiovascular regulatory centers by the cyst explain the sudden death in patients harboring a colloid cyst when signs of hydrocephalus or brain herniation are lacking. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4915842848034158

  12. Acid sensing ion channel 1 in lateral hypothalamus contributes to breathing control.

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    Nana Song

    Full Text Available Acid-sensing ion channels (ASICs are present in neurons and may contribute to chemoreception. Among six subunits of ASICs, ASIC1 is mainly expressed in the central nervous system. Recently, multiple sites in the brain including the lateral hypothalamus (LH have been found to be sensitive to extracellular acidification. Since LH contains orexin neurons and innervates the medulla respiratory center, we hypothesize that ASIC1 is expressed on the orexin neuron and contributes to acid-induced increase in respiratory drive. To test this hypothesis, we used double immunofluorescence to determine whether ASIC1 is expressed on orexin neurons in the LH, and assessed integrated phrenic nerve discharge (iPND in intact rats in response to acidification of the LH. We found that ASIC1 was co-localized with orexinA in the LH. Microinjection of acidified artificial cerebrospinal fluid increased the amplitude of iPND by 70% (pH 7.4 v.s. pH 6.5:1.05±0.12 v.s. 1.70±0.10, n = 6, P<0.001 and increased the respiratory drive (peak amplitude of iPND/inspiratory time, PA/Ti by 40% (1.10±0.23 v.s. 1.50±0.38, P<0.05. This stimulatory effect was abolished by blocking ASIC1 with a nonselective inhibitor (amiloride 10 mM, a selective inhibitor (PcTX1, 10 nM or by damaging orexin neurons in the LH. Current results support our hypothesis that the orexin neuron in the LH can exert an excitation on respiration via ASIC1 during local acidosis. Since central acidification is involved in breathing dysfunction in a variety of pulmonary diseases, understanding its underlying mechanism may improve patient management.

  13. Lipopolysaccharide-induced neuronal activation in the paraventricular and dorsomedial hypothalamus depends on ambient temperature.

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    Samuel P Wanner

    Full Text Available Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS. To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously either in a thermoneutral (30 °C or cool (24 °C environment. At 30 °C, LPS caused fever; at 24 °C, the same dose caused profound hypothermia. Both fever and hypothermia were associated with the induction of c-Fos in many brain areas, including several structures of the anterior preoptic, paraventricular, lateral, and dorsal hypothalamus, the bed nucleus of the stria terminalis, the posterior pretectal nucleus, ventrolateral periaqueductal gray, lateral parabrachial nucleus, area postrema, and nucleus of the solitary tract. Every brain area studied showed a comparable response to LPS at the two different ambient temperatures used, with the exception of two areas: the dorsomedial hypothalamic nucleus (DMH, which we studied together with the adjacent dorsal hypothalamic area (DA, and the paraventricular hypothalamic nucleus (PVH. Both structures had much stronger c-Fos expression during LPS hypothermia than during fever. We propose that PVH and DMH/DA neurons are involved in a circuit, which - depending on the ambient temperature - determines whether the thermoregulatory response to bacterial LPS will be fever or hypothermia.

  14. Angiotensin II Reduces Food Intake by Altering Orexigenic Neuropeptide Expression in the Mouse Hypothalamus

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    Yoshida, Tadashi; Semprun-Prieto, Laura; Wainford, Richard D.; Sukhanov, Sergiy; Kapusta, Daniel R.

    2012-01-01

    Angiotensin II (Ang II), which is elevated in many chronic disease states such as end-stage renal disease and congestive heart failure, induces cachexia and skeletal muscle wasting by increasing muscle protein breakdown and reducing food intake. Neurohormonal mechanisms that mediate Ang II-induced appetite suppression are unknown. Consequently, we examined the effect of Ang II on expression of genes regulating appetite. Systemic Ang II (1 μg/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin, adiponectin, glucagon-like peptide, peptide YY, or cholecystokinin levels. These effects were completely blocked by the Ang II type I receptor antagonist candesartan or deletion of Ang II type 1a receptor. Ang II markedly reduced phosphorylation of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate Npy expression. Intracerebroventricular Ang II infusion (50 ng/kg · min) caused a reduction of food intake, and Ang II dose dependently reduced Npy and orexin expression in the hypothalamus cultured ex vivo. The reduction of Npy and orexin in hypothalamic cultures was completely prevented by candesartan or the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside. Thus, Ang II type 1a receptor-dependent Ang II signaling reduces food intake by suppressing the hypothalamic expression of Npy and orexin, likely via AMPK dephosphorylation. These findings have major implications for understanding mechanisms of cachexia in chronic disease states such as congestive heart failure and end-stage renal disease, in which the renin-angiotensin system is activated. PMID:22234465

  15. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis.

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    Kendall Gillies

    2016-04-01

    Full Text Available Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants or qualitative (relative change from control values approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across

  16. Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation

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    Nasibe Akbari

    2014-02-01

    Full Text Available Introduction: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard.  Methods: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R blocking administered in CSF.  Results: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867 and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity.  Discussion: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process.

  17. 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.

  18. Efferent connections of the parvalbumin-positive (PV1) nucleus in the lateral hypothalamus of rodents.

    Science.gov (United States)

    Celio, Marco R; Babalian, Alexandre; Ha, Quan Hue; Eichenberger, Simone; Clément, Laurence; Marti, Christiane; Saper, Clifford B

    2013-10-01

    A solitary cluster of parvalbumin-positive neurons--the PV1 nucleus--has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the PV1 nucleus using nonspecific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1 nucleus was found to project mainly to the periaqueductal grey matter (PAG), predominantly ipsilaterally. Indirectly in rats and directly in mice, a discrete, longitudinally oriented cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF is particularly dense in the rostral portion, which is located in the supraoculomotor nucleus (Su3). It is spatially interrupted over a short stretch at the level of the trochlear nucleus and abuts caudally on a second parvalbumin-positive (PV2) nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings, which stem from neurons scattered throughout the PV1 nucleus. Topographically, the longitudinal orientation of the PV1-CTF accords with that of the likewise longitudinally oriented functional modules of the PAG, but overlaps none of them. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger-Westphal, the lateral habenular, and the laterodorsal tegmental nuclei. So far, no obvious functions have been attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1 nucleus. © 2013 Wiley Periodicals, Inc.

  19. Plasma, cerebrospinal fluid, and brain distribution of 14C-melatonin in rat: a biochemical and autoradiographic study

    International Nuclear Information System (INIS)

    Vitte, P.A.; Harthe, C.; Lestage, P.; Claustrat, B.; Bobillier, P.

    1988-01-01

    The distribution of 14C-Melatonin (14C-MT) after systemic injection was studied in the plasma, cerebrospinal fluid (CSF), and brain of rats. Chromatographic analysis (thin-layer chromatography and high-performance liquid chromatography) indicated that the radioactivity from biological samples taken at various times following the injection of label was mainly associated with 14C-MT. Computer analysis of plasma 14C-MT kinetics showed a three-compartment system with half-lives of 0.21 +/- 0.05, 5.97 +/- 1.11, and 47.52 +/- 8.86 min. The volume of distribution and the clearance were 1,736 +/- 349 ml.kg-1 and 25.1 +/- 1.7 ml.min-1.kg-1 respectively. The entry of 14C-MT into the CSF was rapid and reached a maximum at 5 min. The decay followed a two-compartment system with half-lives of 16.5 +/- 2.9 and 47.3 +/- 8.6 min. The CSF/plasma concentration ratio was 0.38 at the steady state (30 min). At 2 min the level of 14C-MT in the brain was 3.8 higher than in the CSF. Representative autoradiograms revealed an heterogeneous localization of 14C-MT in the grey matter. The highest regional values, as evaluated by the permeability area product technique, were found in cortex, thalamic nuclei, medial geniculate nucleus, anterior pretectal area, paraventricular nucleus of the hypothalamus, choroid plexuses, and bulb-pons. Thirty minutes later 14C-MT was still detected in most of the brain regions analyzed. These results point to a low but rapid penetration of circulating MT into the brain and the CSF. The heterogeneous distribution and the partial retention of 14C-MT in the brain are compatible with the hypothesis of a central action of this hormone mediated via binding sites

  20. Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review.

    Science.gov (United States)

    Auvinen, H E; Romijn, J A; Biermasz, N R; Havekes, L M; Smit, J W A; Rensen, P C N; Pereira, A M

    2011-12-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the hypothalamus-pituitary-adrenal-axis activation. The aim of this review was to assess the effects of high fat feeding on the activity of the hypothalamus-pituitary-adrenal-axis in mice. PubMed, EMBASE, Web of Science, the Cochrane database, and Science Direct were electronically searched and reviewed by 2 individual researchers. We included only original mouse studies reporting parameters of the hypothalamus-pituitary-adrenal-axis after high fat feeding, and at least 1 basal corticosterone level with a proper control group. Studies with adrenalectomized mice, transgenic animals only, high fat diet for less than 2 weeks, or other interventions besides high fat diet, were excluded. 20 studies were included. The hypothalamus-pituitary-adrenal-axis evaluation was the primary research question in only 5 studies. Plasma corticosterone levels were unchanged in 40%, elevated in 30%, and decreased in 20% of the studies. The effects in the peripheral tissues and the central nervous system were also inconsistent. However, major differences were found between mouse strains, experimental conditions, and the content and duration of the diets. This systematic review demonstrates that the effects of high fat feeding on the basal activity of the hypothalamus-pituitary-adrenal-axis in mice are limited and inconclusive. Differences in experimental conditions hamper comparisons and accentuate the need for standardized evaluations to discern the effects of diet-induced obesity on the hypothalamus-pituitary-adrenal-axis. © Georg Thieme Verlag KG Stuttgart · New York.

  1. In a rat model of night work, activity during the normal resting phase produces desynchrony in the hypothalamus.

    Science.gov (United States)

    Salgado-Delgado, Roberto; Nadia, Saderi; Angeles-Castellanos, M; Buijs, Ruud M; Escobar, Carolina

    2010-12-01

    Internal synchrony among external cycles and internal oscillators allows adaptation of physiology to cyclic demands for homeostasis. Night work and shift work lead to a disrupted phase relationship between external time cues and internal rhythms, also losing internal coherence among oscillations. This process results in internal desynchrony (ID) in which behavioral, hormonal, and metabolic variables cycle out of phase. It is still not clear whether ID originates at a peripheral or at a central level. In order to determine the possible role of hypothalamic oscillators in ID, we explored with a rat model of "night work" daily rhythms of activity and clock gene expression in the hypothalamus. This study provides evidence that wakefulness and activity during the normal resting phase lead to a shift in the diurnal rhythms of c-Fos and induce a rhythm of PER1 in the arcuate and dorsomedial nucleus of the hypothalamus, both associated with metabolism and regulation of the sleep/wake cycle. Moreover, the number of orexin (ORX)-positive neurons and c-Fos in the perifornical area increased during the working period, suggesting a relevant switch of activity in this brain region induced by the scheduled activity; however, the colocalization of c-Fos in ORX-positive cells was not increased. In contrast, the suprachiasmatic nucleus and the paraventricular nucleus remained locked to the light/dark cycle, resulting in ID in the hypothalamus. Present data suggest that ID occurs already at the level of the first output projections from the SCN, relaying nuclei that transmit temporal signals to other brain areas and to the periphery.

  2. Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors.

    Science.gov (United States)

    Follin, Cecilia; Erfurth, Eva Marie

    2016-09-01

    Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.

  3. Preoperative Assessment of Craniopharyngioma Adherence: Magnetic Resonance Imaging Findings Correlated with the Severity of Tumor Attachment to the Hypothalamus.

    Science.gov (United States)

    Prieto, Ruth; Pascual, José M; Rosdolsky, Maria; Barrios, Laura

    2018-02-01

    Craniopharyngioma (CP) adherence represents a heterogeneous pathologic feature that critically influences the potentially safe and radical resection. The aim of this study was to define the magnetic resonance imaging (MRI) predictors of CP adherence severity. This study retrospectively investigated a cohort of 200 surgically treated CPs with their corresponding preoperative conventional MRI scans. MRI findings related to the distortions of anatomic structures along the sella turcica-third ventricle axis caused by CPs, in addition to the tumor's shape and calcifications, were analyzed and correlated with the definitive type of CP adherence observed during the surgical procedures. CP adherence is defined by 3 components, as follows: 1) the specific structures attached to the tumor, 2) the adhesion's extent, and 3) its strength. Combination of these 3 components determines 5 hierarchical levels of adherence severity with gradually increasing surgical risk of hypothalamic injury. Multivariate analysis identified 4 radiologic variables that allowed a correct overall prediction of the levels of CP adherence severity in 81.5% of cases: 1) the position of the hypothalamus in relation to the tumor-the most discriminant factor; 2) the type of pituitary stalk distortion; 3) the tumor shape; and 4) the presence of calcifications. A binary logistic regression model including the first 3 radiologic variables correctly identified the CPs showing the highest level of adherence severity (severe/critical) in almost 90% of cases. A position of the hypothalamus around the middle portion of the tumor, an amputated or infiltrated appearance of the pituitary stalk, and the elliptical shape of the tumor are reliable predictors of strong and extensive CP adhesions to the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Nutrient restriction induces failure of reproductive function and molecular changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.

    Science.gov (United States)

    Zhou, Dongsheng; Zhuo, Yong; Che, Lianqiang; Lin, Yan; Fang, Zhengfeng; Wu, De

    2014-07-01

    People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ≥ 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor α, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function.

  5. α-MSH Influences the Excitability of Feeding-Related Neurons in the Hypothalamus and Dorsal Vagal Complex of Rats

    Directory of Open Access Journals (Sweden)

    Hong-Zai Guan

    2017-01-01

    Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is processed from proopiomelanocortin (POMC and acts on the melanocortin receptors, MC3 and MC4. α-MSH plays a key role in energy homeostasis. In the present study, to shed light on the mechanisms by which α-MSH exerts its anorectic effects, extracellular neuronal activity was recorded in the hypothalamus and the dorsal vagal complex (DVC of anesthetized rats. We examined the impact of α-MSH on glucose-sensing neurons and gastric distension (GD sensitive neurons. In the lateral hypothalamus (LHA, α-MSH inhibited 75.0% of the glucose-inhibited (GI neurons. In the ventromedial nucleus (VMN, most glucose-sensitive neurons were glucose-excited (GE neurons, which were mainly activated by α-MSH. In the paraventricular nucleus (PVN, α-MSH suppressed the majority of GI neurons and excited most GE neurons. In the DVC, among the 20 GI neurons examined for a response to α-MSH, 1 was activated, 16 were depressed, and 3 failed to respond. Nineteen of 24 GE neurons were activated by α-MSH administration. Additionally, among the 42 DVC neurons examined for responses to GD, 23 were excited (GD-EXC and 19 were inhibited (GD-INH. Fifteen of 20 GD-EXC neurons were excited, whereas 11 out of 14 GD-INH neurons were suppressed by α-MSH. All these responses were abolished by pretreatment with the MC3/4R antagonist, SHU9119. In conclusion, the activity of glucose-sensitive neurons and GD-sensitive neurons in the hypothalamus and DVC can be modulated by α-MSH.

  6. Exposure to a complex cocktail of environmental endocrine-disrupting compounds disturbs the kisspeptin/GPR54 system in ovine hypothalamus and pituitary gland.

    Science.gov (United States)

    Bellingham, Michelle; Fowler, Paul A; Amezaga, Maria R; Rhind, Stewart M; Cotinot, Corinne; Mandon-Pepin, Beatrice; Sharpe, Richard M; Evans, Neil P

    2009-10-01

    Ubiquitous environmental chemicals, including endocrine-disrupting chemicals (EDCs), are associated with declining human reproductive health, as well as an increasing incidence of cancers of the reproductive system. Verifying such links requires animal models exposed to "real-life," environmentally relevant concentrations/mixtures of EDC, particularly in utero, when sensitivity to EDC exposure is maximal. We evaluated the effects of maternal exposure to a pollutant cocktail (sewage sludge) on the ovine fetal reproductive neuroendocrine axes, particularly the kisspeptin (KiSS-1)/GPR54 (G-protein-coupled receptor 54) system. KiSS-1, GPR54, and ERalpha (estrogen receptor alpha) mRNA expression was quantified in control (C) and treated (T) maternal and fetal (110-day) hypothalami and pituitary glands using semiquantitative reverse transcription polymerase chain reaction, and colocalization of kisspeptin with LHbeta (luteinizing hormone beta) and ERalpha in C and T fetal pituitary glands quantified using dual-labeling immunohistochemistry. Fetuses exposed in utero to the EDC mixture showed reduced KiSS-1 mRNA expression across three hypothalamic regions examined (rostral, mid, and caudal) and had fewer kisspetin immunopositive cells colocalized with both LHbeta and ERalpha in the pituitary gland. In contrast, treatment had no effect on parameters measured in the adult ewe hypothalamus or pituitary. This study demonstrates that the developing fetus is sensitive to real-world mixtures of environmental chemicals, which cause significant neuroendocrine alterations. The important role of kisspeptin/GPR54 in regulating puberty and adult reproduction means that in utero disruption of this system is likely to have long-term consequences in adulthood and represents a novel, additional pathway through which environmental chemicals perturb human reproduction.

  7. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

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    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  8. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    International Nuclear Information System (INIS)

    Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

    2001-01-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  9. Peripheral Injection of SB203580 Inhibits the Inflammatory-Dependent Synthesis of Proinflammatory Cytokines in the Hypothalamus

    Directory of Open Access Journals (Sweden)

    Andrzej P. Herman

    2014-01-01

    Full Text Available The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL- 1β, IL-6, and tumor necrosis factor (TNF α in the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS (400 ng/kg over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK, which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFα synthesis. Intravenous injection of SB203580 successfully inhibited (P<0.01 synthesis of IL-1β and reduced (P<0.01 the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P<0.01 gene expression of TNFα but its effect was not observed at the level of TNFα protein synthesis. SB203580 also reduced (P<0.01 LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.

  10. Reversible inactivation of the lateral hypothalamus reversed high reward choices in cost-benefit decision-making in rats.

    Science.gov (United States)

    Karimi, Sara; Mesdaghinia, Azam; Farzinpour, Zahra; Hamidi, Gholamali; Haghparast, Abbas

    2017-11-01

    The Lateral hypothalamus (LH) is an important component of the networks underlying the control of feeding and other motivated behaviors. Cost-benefit decision-making is mediated largely by the prefrontal cortex (PFC) which strongly innervates the LH. Therefore, in the current study, we conducted a series of experiments to elucidate the role of the perifornical area of the lateral hypothalamus (PeF-LH) in effort and/or delay-based decision-making. We trained different groups of rats in a delay-based and/or an effort-based form of cost-benefit T-maze decision- making task in which they could either choose to pay the cost to obtain a high reward in one arm or could obtain a low reward in the other arm with no cost. During test days, the rats received local injections of either vehicle or lidocaine4% (0.5 μl/side), in the PeF-LH. In an effort-based decision task, PeF-LH inactivation led to decrease in high reward choice. Similarly, in a delay-based decision task animals' preference changed to a low but immediately available reward. This was not caused by a spatial memory or motor deficit. PeF-LH inactivation modified decision behavior. The results imply that PeF-LH is important for allowing the animal to pay a cost to acquire greater rewards. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. [Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].

    Science.gov (United States)

    Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie

    2003-06-01

    To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.

  12. The tuberal lateral hypothalamus is a major target for GABAA--but not GABAB-mediated control of food intake.

    Science.gov (United States)

    Turenius, Christine I; Charles, Jonathan R; Tsai, Donna H; Ebersole, Priscilla L; Htut, Myat H; Ngo, Phuong T; Lara, Raul N; Stanley, B Glenn

    2009-08-04

    The lateral hypothalamus (LH) is a site of integration for control mechanisms of feeding behavior as it has extensive reciprocal connections with multiple intrahypothalamic and extrahypothalamic brain areas. Evidence suggests that blockade of ionotropric gamma-aminobutyric acid (GABA) receptors in the LH elicits eating in satiated rats. To determine whether this GABA(A) receptor antagonist effect is specific to the LH, the antagonist picrotoxin was injected into one of six nearby sites and food intake was measured. Picrotoxin at 133 pmol elicited eating in the LH, but not in surrounding sites (thalamus, lateral preoptic area, ventral tegmental area, dorsomedial hypothalamus, and entopeduncular nucleus). More specifically, picrotoxin injected into the tuberal LH (tLH) elicited eating, but was ineffective when injected into the anterior or posterior LH. We also investigated whether GABA(B) receptors in the LH participated in the control of food intake and found that neither blockade nor activation of these receptors under multiple conditions changed food intake. Collectively, our findings suggest that GABA(A) but not GABA(B) receptors in the tLH act to suppress feeding behavior.

  13. Evidence for the Presence of Glucosensor Mechanisms Not Dependent on Glucokinase in Hypothalamus and Hindbrain of Rainbow Trout (Oncorhynchus mykiss.

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    Cristina Otero-Rodiño

    Full Text Available We hypothesize that glucosensor mechanisms other than that mediated by glucokinase (GK operate in hypothalamus and hindbrain of the carnivorous fish species rainbow trout and stress affected them. Therefore, we evaluated in these areas changes in parameters which could be related to putative glucosensor mechanisms based on liver X receptor (LXR, mitochondrial activity, sweet taste receptor, and sodium/glucose co-transporter 1 (SGLT-1 6 h after intraperitoneal injection of 5 mL x Kg(-1 of saline solution alone (normoglycaemic treatment or containing insulin (hypoglycaemic treatment, 4 mg bovine insulin x Kg(-1 body mass, or D-glucose (hyperglycaemic treatment, 500 mg x Kg(-1 body mass. Half of tanks were kept at a 10 Kg fish mass x m(-3 and denoted as fish under normal stocking density (NSD whereas the remaining tanks were kept at a stressful high stocking density (70 kg fish mass x m(-3 denoted as HSD. The results obtained in non-stressed rainbow trout provide evidence, for the first time in fish, that manipulation of glucose levels induce changes in parameters which could be related to putative glucosensor systems based on LXR, mitochondrial activity and sweet taste receptor in hypothalamus, and a system based on SGLT-1 in hindbrain. Stress altered the response of parameters related to these systems to changes in glycaemia.

  14. Glucostatic regulation of (+)-[3H]amphetamine binding in the hypothalamus: correlation with Na+, K+-ATPase activity

    International Nuclear Information System (INIS)

    Angel, I.; Hauger, R.L.; Luu, M.D.; Giblin, B.; Skolnick, P.; Paul, S.M.

    1985-01-01

    Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37 0 C) resulted in a time-dependent decrease in specific (+)-[ 3 H]amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-[ 3 H]amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[ 3 H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[ 3 H]amphetamine binding, suggesting the involvement of Na + , K + -ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na + ,K + -ATPase activity and the number of specific high-affinity binding sites for [ 3 H]ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-[ 3 H]amphetamine and [ 3 H]ouabain binding. These data suggest that the (+)-[ 3 H]amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na + ,K + -ATPase activity, and the latter may be involved in the glucostatic regulation of appetite

  15. Effect of chronic exposure to gamma radiation and of hormonal stimulation with serum gonadotropin on catecholamine levels in hypothalamus, epiphysis and adrenals of ewes

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.

    1989-01-01

    The effects were studied of exposure to whole body continuous irradiation and of the administration of serum gonadotropin (SG) on the concentration of catecholamines (epinephrine and norepinephrine) in the hypothalamus, epiphysis and adrenal glands of ewes during the anestric period with synchronized estrus. The first group (young barren ewes) and second group (older ewes) were exposed to continuous radiation of 60 Co for five days. The radiation was applied at a rate of 0.020 Gy per hour. After the termination of irradiation the ewes were subjected to hormonal stimulation by fractionated administration of 1500 I.U. SG. The third and fourth experimental groups of ewes were stimulated with 1500 I.U. SG without irradiation. Catecholamines were separated from the tissue supernatants by adsorption chromatography and the catecholamine contents in the eluates were determined spectrofluorometrically. Chronic exposure to gamma radiation and hormonal stimulation with SG reduced the concentration of norepinephrine in the whole hypothalamus of the sheep. A statistically significant decrease (P<0.001) was recorded in the medial and caudal hypothalamus of the adult ewes and in the rostral and caudal hypothalamus regions of the young ewes. A decrease in norepinephrine concentration, statistically significant in the caudal (P<0.01) and medial hypothalamus was recorded in the group of adult ewes after hormonal stimulation with SG without irradiation. The experimental group of young ewes responded to hormonal stimulation by a greater reduction of norepinephrine contents as compared with combined exposure to radiation and hormonal stimulation. It is assumed that the decrease in catecholamine concentration after hormonal stimulation with SG is associated with the increase in the contents of estrogens which act on the adrenergic receptors of the hypothalamus. (author). 4 figs., 21 refs

  16. Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins, ACTH, MSH and beta-LPH.

    Science.gov (United States)

    Bugnon, C; Bloch, B; Lenys, D; Fellmann, D

    1979-06-27

    In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin.

  17. Hypothalamus-pituitary-thyroid axis disruption in rats with breast cancer is related to an altered endogenous oxytocin/insulin-regulated aminopeptidase (IRAP) system.

    Science.gov (United States)

    Carrera-González, María Pilar; Ramírez-Expósito, María Jesús; de Saavedra, Jose Manuel Arias; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, Jose Manuel

    2011-06-01

    Associations of breast cancer with diseases of the thyroid have been repeatedly reported, but the mechanism underlying this association remains to be elucidated. It has been reported that oxytocin (OXT) attenuates the thyroid-stimulating hormone (TSH) release in response to thyrotrophin-releasing hormone (TRH) and decreased plasma levels of TSH as well as the thyroid hormones by an effect mediated by the central nervous system. Oxytocinase (IRAP) is the regulatory proteolytic enzyme reported to hydrolyze OXT. Changes in IRAP activity have been reported in both human breast cancer and N-methyl-nitrosourea (NMU)-induced rat mammary tumours. Here, we measure IRAP activity fluorometrically using cystyl-β-naphthylamide as the substrate, in the hypothalamus-pituitary-thyroid axis together with the circulating levels of OXT, and its relationship with circulating levels of TSH and free thyroxine (fT4), as markers of thyroid function in control rats and rats with breast cancer induced by NMU. We found decreased thyroid function in rats with breast cancer induced by NMU, supported by the existence of lower serum circulating levels of both TSH and fT4 than their corresponding controls. Concomitantly, we found a decrease of hypothalamic IRAP activity and an increase in circulating levels of OXT. We propose that breast cancer increases OXT pituitary release by decreasing its hypothalamic catabolism through IRAP activity, probably due to the alteration of the estrogenic endocrine status. Thus, high circulating levels of OXT decreased TSH release from the pituitary, and therefore, of thyroid hormones from the thyroid, supporting the association between breast cancer and thyroid function disruption.

  18. Repeated in vivo exposure of cocaine induces long-lasting synaptic plasticity in hypocretin/orexin-producing neurons in the lateral hypothalamus in mice.

    Science.gov (United States)

    Rao, Yan; Mineur, Yann S; Gan, Geliang; Wang, Alex Hanxiang; Liu, Zhong-Wu; Wu, Xinyuan; Suyama, Shigetomo; de Lecea, Luis; Horvath, Tamas L; Picciotto, Marina R; Gao, Xiao-Bing

    2013-04-01

    Hypocretin (orexin), a neuropeptide synthesized exclusively in the perifornical/lateral hypothalamus, is critical for drug seeking and relapse, but it is not clear how the circuitry centred on hypocretin-producing neurons (hypocretin neurons) is modified by drugs of abuse and how changes in this circuit might alter behaviours related to drug addiction. In this study, we show that repeated, but not single, in vivo cocaine administration leads to a long-lasting, experience-dependent potentiation of glutamatergic synapses on hypocretin neurons in mice following a cocaine-conditioned place preference (CPP) protocol. The synaptic potentiation occurs postsynaptically and probably involves up-regulation of AMPA-type glutamate receptors on hypocretin neurons. Phosphorylation of cAMP response element-binding protein (CREB) is also significantly increased in hypocretin neurons in cocaine-treated animals, suggesting that CREB-mediated pathways may contribute to synaptic potentiation in these cells. Furthermore, the potentiation of synaptic efficacy in hypocretin neurons persists during cocaine withdrawal, but reverses to baseline levels after prolonged abstinence. Finally, the induction of long-term potentiation (LTP) triggered by a high-frequency stimulation is facilitated in hypocretin neurons in cocaine-treated mice, suggesting that long-lasting changes in synapses onto hypocretin neurons would probably be further potentiated by other stimuli (such as concurrent environmental cues) paired with the drug. In summary, we show here that hypocretin neurons undergo experience-dependent synaptic potentiation that is distinct from that reported in other reward systems, such as the ventral tegmental area, following exposure to cocaine. These findings support the idea that the hypocretin system is important for behavioural changes associated with cocaine administration in animals and humans.

  19. Effect of thyrotropin-releasing hormone (TRH) on local cerebral glucose utilization, by the autoradiographic 2-deoxy [14C] glucose method, in conscious and pentobarbitalized rats

    International Nuclear Information System (INIS)

    Nagai, Y.; Narumi, S.; Nagawa, Y.; Sakurada, O.; Ueno, H.; Ishii, S.

    1980-01-01

    Effects of TRH and pentobarbital alone, and in combination, on local cerebral glucose utilization of rats were studied by the autoradiographic 2-deoxy[ 14 C] glucose method. TRH (5 mg/kg i.v.) reduced the rate of cerebral glucose utilization slightly in the whole brain. Locally, significant depression was observed in the following structures: frontal and visual cortices, hippocampus Ammon's horn and dentate gyrus, medial and lateral geniculate bodies, nucleus accumbens, caudate-putamen, substantia nigra, pontine gray matter, superior colliculus, superior olivary nucleus, vestibular nucleus, lateral lemniscus and cerebellar cortex. Pentobarbital (30 mg/kg i.v.) produced a marked and diffuse reduction in the rate of glucose utilization throughout the brain. TRH given 15 min after the administration of pentobarbital markedly shortened the pentobarbital sleeping time and caused some reversal of the depression in local cerebral glucose utilization produced by pentobarbital., These effects were almost completely abolished by pretreatment with intracerebroventricular injection of atropine methyl bromide (20 μg/rat). These results indicate that although TRH acts to cause a reduction in the rate of cerebral glucose utilization, it reverses the depression induced by pentobarbital, via a cholinergic mechanism, in a number of structures, some of which are related to monoaminergic systems and the reticulo-thalamo-cortical activating system. (author)

  20. An autoradiographic study of the synthesis of nucleic acids and protein during the cell cycle of synchronously dividing antheridial filaments in Chara vulgaris L

    Energy Technology Data Exchange (ETDEWEB)

    Olszewska, M J; Godlewski, M [Lodz Univ. (Poland)

    1972-01-01

    The synthesis of DNA, RNA, and protein in successive mitotic cycles of the synchronously dividing antheridial filaments of Chara vulgaris was studied autoradiographically. In all the generations examined, which enter the next mitosis, i.e., in the 4-, 8-, 16-, and 32-cell generations, the synthesis of DNA begins as early as telephase and continues into the early stages of interphase. The telephase cells of the 32-cell filaments do not incorporate //sup 3/H/thymidine, because the cells which arise from them do not divide but are transformed into spermatozoa. The DNA synthesis is accompanied by intense synthesis of RNA. The intensity of radioactivity calculated for 100 ..mu../sup 2/ of the area of the nucleus and cytoplasm is similar in all the generations, whereas the radioactivity induced by the incorporation of /8-/sup 14/C/adenine and//sup 3/H/phenylalanine calculated for one cell decreases proportionally to the reduction of the volume of the cytoplasm and nucleus in successive generations. (auth)

  1. Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis

    International Nuclear Information System (INIS)

    Black, J.D.; Dolly, J.O.

    1986-01-01

    Using pharmacological and autoradiographic techniques it has been shown that botulinum neurotoxin (BoNT) is translocated across the motor nerve terminal membrane to reach a postulated intraterminal target. In the present study, the nature of this uptake process was investigated using electron microscopic autoradiography. It was found that internalization is acceptor-mediated and that binding to specific cell surface acceptors involves the heavier chain of the toxin. In addition, uptake was shown to be energy and temperature-dependent and to be accelerated by nerve stimulation, a treatment which also shortens the time course of the toxin-induced neuroparalysis. These results, together with the observation that silver grains were often associated with endocytic structures within the nerve terminal, suggested that acceptor-mediated endocytosis is responsible for toxin uptake. Possible recycling of BoNT acceptors (an important aspect of acceptor-mediated endocytosis of toxins) at motor nerve terminals was indicated by comparing the extent of labeling in the presence and absence of metabolic inhibitors. On the basis of these collective results, it is concluded that BoNT is internalized by acceptor-mediated endocytosis and, hence, the data support the proposal that this toxin inhibits release of acetylcholine by interaction with an intracellular target

  2. Fate and role of macromolecules synthesized during mammalian oocyte meiotic maturation. II. - Autoradiographic topography of (/sup 3/H)-fucose incorporation in pig oocytes cultured in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Pivko, J. (Animal Production Research Institute, Nitra (Czechoslovakia)); Motlik, J. (Institute of Animal Physiology and Genetics, Libechov (Czechoslovakia)); Kopecny, V. (University J.E. Purkyne, Brno (Czechoslovakia)); Flechon, J.E. (I.N.R.A., Station Centrale de Physiologie Animale, Jouy-en-Josas (France))

    1982-01-01

    Pig oocytes in different maturational stages--germinal vesicle (GV), metaphase I (MI) and metaphase II (MII)- were cultured in vitro with (/sup 3/H)-fucose. The incorporation of the precursor was followed by LM or EM autoradiography on air-dried preparations and on semithin or thin sections. The cumulus cells connected with oocytes at the GV stage were intensely labelled, while the labelling of the cumulus of MI and MII oocytes was lower. The cytoplasm of oocytes in the GV stage was characterized by nests of silver grains located mainly in a juxtanuclear position. The accumulation of label in the cortical region, observed in oocytes cultured with an intact cumulus, was less evident in cumulus-deprived oocytes. Lower labelling of the ooplasm, together with uniform distribution of the grains, was observed in later stages of meiosis. EM autoradiographs demonstrated the main localization, at the GV stage, of label in the Golgi apparatus and near the cell surface of oocytes and cumulus cells, as well as in the cytoplasmic processes of corona radiata cells. It is concluded that a relatively intense glycoprotein synthesis takes place in pig oocytes and cumulus cells during resumption of meiosis, at least before GV breakdown. Metabolic cooperation may occur as long as oocytes and cumulus cells keep membrane junctions.

  3. Autoradiographic analysis of 3H-glutamate, 3H-dopamine, and 3H-GABA accumulation in rabbit retina after kainic acid treatment

    International Nuclear Information System (INIS)

    Hampton, C.K.; Redburn, D.A.

    1983-01-01

    We have previously reported that exposure of isolated rabbit retina to 10(-3) M kainic acid produces profound morphological changes in specific retinal neurons (Hampton et al, 1981). We noted specific swelling of horizontal cell bodies and neurites, necrosis of cell bodies in the amacrine and ganglion cell layers, and swelling of elements in the inner plexiform layer. We now report a differential sensitivity to kainic acid of specific subclasses of amacrine cells autoradiographically labeled with 3H-glutamate, 3H-GABA, or 3H-dopamine. Three different effects were observed: (1) Labeling of neurons after incubation in 3H-glutamate was uniformly reduced while labeling of glia was much less affected. (2) The accumulation of 3H-dopamine was also decreased by kainic acid in two of the three labeled bands of the inner plexiform layer. The outermost labeled band was insensitive to kainic acid at the highest concentration tested (10(-2) M). These findings provide a basis for the subclassification of dopaminergic amacrine cells into at least two subclasses based on their sensitivity to kainic acid. (3) Kainic acid caused a dramatic increase in the labeling of GABAergic amacrine cell bodies and their terminals. This increased intensity may reflect a compensatory increase in uptake activity in response to kainic acid-induced depletion of endogenous GABA stores. These results confirm the highly toxic nature of kainic acid and demonstrate a high degree of specificity and complexity in its action in the retina

  4. Evaluation of autoradiographs and images of biological objects with the electronically operating image analyzer 'Densitron II'. II. Determination of the specific and total radioactivity of single cells

    Energy Technology Data Exchange (ETDEWEB)

    Hess, J; Korn, U; Freyer, K; Ermisch, A [Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften; Akademie der Wissenschaften der DDR, Leipzig. Zentralinstitut fuer Isotopen- und Strahlenforschung)

    1976-01-01

    Using the TV image analyzer Densitron, transparencies and areas can be measured by the grey value discrimination method equidensitometry. The time, necessary for one measurement, is approximately 1 min, the standard deviations do not exceed 2%. Microscopical objects such as single cells can be analyzed by this method. Photo-blackings and areas have been measured in autoradiographs of goldfish brain-sections after injection of /sup 3/H-phenylalanine. As a parallel, blacking and area calibration curves were obtained which allowed a conversion of the relative values into absolute ones. Using this conversion method, neurons of different brain regions were in the range from 104 to 1476..mu..m/sup 2/ in area and from 4.17 to 14.43..mu..Ci . cm/sup -3/ in specific radioactivity. The standard deviations of the absolute values were 6 and 4.5%, respectively. On the basis of these and additional values (thickness of section, number of sections per cell), calculations of the total radioactivity of a cell section or the whole cell can be made.

  5. Acetylcholine receptors in the human retina

    International Nuclear Information System (INIS)

    Hutchins, J.B.; Hollyfield, J.G.

    1985-01-01

    Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand 3 H-propylbenzilylcholine mustard ( 3 H-PrBCM) to label muscarinic receptors. 3 H- or 125 I-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that 3 H-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer of the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. This study provides evidence for cholinergic neurotransmission in the human retina

  6. [Age-related changes in biogenic amine content and oxidative stress profile in the rat hypothalamus in hyperhomocysteinemia].

    Science.gov (United States)

    Milyutina, Yu P; Pustygina, A V; Zaloznyaya, I V; Arutjunyan, A V

    2016-01-01

    The article presents a detailed analysis of correlations between the content of a variety of biogenic amines in the hypothalamic structures responsible for the luteinizing hormone releasing hormone synthesis and secretion (the medial preoptic area and median eminence) and such independent factors as total L-homocysteine plasma level elevation induced by L-methionine loading and aging. Both a nature and a pattern of changes in oxidative stress profile were evaluated. It was shown that ageing, when compared to hyperhomocysteinemia, is a determining factor influencing biogenic amine content in the studied hypothalamic structures. Unlike antioxidant defense system profile, considerable changes in macromolecule oxidative modification were not found, which evidences a balanced activity of pro- and antioxidant systems in the hypothalamus.

  7. Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight

    Directory of Open Access Journals (Sweden)

    Saira Hameed

    2017-06-01

    Full Text Available The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs, which function as ligand-inducible transcription factors. The TR-beta isoform (TRβ is expressed in the ventromedial hypothalamus (VMH, a brain area important for control of energy homeostasis. Here, we report that selective knockdown of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis.

  8. [Changes in the monoamine content in different parts of hypothalamus depending on the stages of the estrous cycle].

    Science.gov (United States)

    Babichev, V N; Adamskaia, E I

    1976-01-01

    Fluorimetric determination of monoamines in various regions of the hypothalamus and at different stages of the estral cycle in rats showed that the serotonin, noradrenaline, and particularly dophamine content changed both in the course of the cycle and at different time (10, 15 and 18 hours) of the same stage of the cycle. Dophamine concentration in the arcuate area--the centre of the tonic activity--reached its maximum at 18 hours of the diestrus-2 (D2) and fell to the minimum at 10 hours of the proestrus (P). Noradrenaline level in the preoptic area increased at 18 hours of the D2 and fell at 10 hours of the P. It is supposed that in the hypothalamic regulation of the estral cycle at least two monoamines (dopamine and noradrenaline) took part; the trigger role belongs to noradrenaline of the preoptic area (the cyclic centre).

  9. Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal.

    Directory of Open Access Journals (Sweden)

    Bernadett Pintér-Kübler

    Full Text Available Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH, urocortin 2 (UCN2 and proopiomelanocortin (POMC compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15-30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY and arginine vasopressin (AVP mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls.

  10. Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice.

    Science.gov (United States)

    Laperrousaz, Elise; Moullé, Valentine S; Denis, Raphaël G; Kassis, Nadim; Berland, Chloé; Colsch, Benoit; Fioramonti, Xavier; Philippe, Erwann; Lacombe, Amélie; Vanacker, Charlotte; Butin, Noémie; Bruce, Kimberley D; Wang, Hong; Wang, Yongping; Gao, Yuanqing; Garcia-Caceres, Cristina; Prévot, Vincent; Tschöp, Matthias H; Eckel, Robert H; Le Stunff, Hervé; Luquet, Serge; Magnan, Christophe; Cruciani-Guglielmacci, Céline

    2017-07-01

    Regulation of energy balance involves the participation of many factors, including nutrients, among which are circulating lipids, acting as peripheral signals informing the central nervous system of the energy status of the organism. It has been shown that neuronal lipoprotein lipase (LPL) participates in the control of energy balance by hydrolysing lipid particles enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation of metabolic homeostasis, could also contribute to the regulation of body weight and glucose homeostasis. We injected an adeno-associated virus (AAV) expressing Cre-green fluorescent protein into the MBH of Lpl-floxed mice (and wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then studied energy homeostasis and hypothalamic ceramide content. The partial deletion of Lpl in the MBH in mice led to an increase in body weight compared with controls (37.72 ± 0.7 g vs 28.46 ± 0.12, p < 0.001) associated with a decrease in locomotor activity. These mice developed hyperinsulinaemia and glucose intolerance. This phenotype also displayed reduced expression of Cers1 in the hypothalamus as well as decreased concentration of several C18 species of ceramides and a 3-fold decrease in total ceramide intensity. Conversely, overexpression of Lpl specifically in the MBH induced a decrease in body weight. Our study shows that LPL in the MBH is an important regulator of body weight and glucose homeostasis.

  11. Exposure to chronic isolation modulates receptors mRNAs for oxytocin and vasopressin in the hypothalamus and heart.

    Science.gov (United States)

    Pournajafi-Nazarloo, Hossein; Kenkel, William; Mohsenpour, Seyed Ramezan; Sanzenbacher, Lisa; Saadat, Habibollah; Partoo, Leila; Yee, Jason; Azizi, Fereidoun; Carter, C Sue

    2013-05-01

    The goal of our study was to explore the effect of social isolation stress of varying durations on the plasma oxytocin (OT), messenger ribonucleic acid (mRNA) for oxytocin receptor (OTR), plasma arginine vasopressin (AVP) and mRNA for V1a receptor of AVP (V1aR) expression in the hypothalamus and heart of socially monogamous female and male prairie voles (Microtus ochrogaster). Continuous isolation for 4 weeks (chronic isolation) increased plasma OT level in females, but not in males. One hour of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma AVP level. Chronic isolation, but not repeated isolation, significantly decreased OTR mRNA in the hypothalamus and heart in both sexes. Chronic isolation significantly decreased cardiac V1aR mRNA, but no effect on hypothalamic V1aR mRNA expression. We did not find a gender difference within repeated social isolation groups. The results of the present study reveal that although chronic social isolation can down-regulate gene expression for the OTR in both sexes, the release of the OT peptide was increased after chronic isolation only in females, possibly somewhat protecting females from the negative consequences of isolation. In both sexes repeated, but not chronic, isolation increased plasma AVP, which could be permissive for mobilization and thus adaptive in response to a repeated stressor. The differential effects of isolation on OT and AVP systems may help in understanding mechanisms through social interactions can be protective against emotional and cardiovascular disorders. Published by Elsevier Inc.

  12. Expression of stress hormones AVP and CRH in the hypothalamus of Mus musculus following water and food deprivation.

    Science.gov (United States)

    Yadawa, Arun Kumar; Chaturvedi, Chandra Mohini

    2016-12-01

    Neurohypophyseal hormone, arginine vasopressin (AVP), in addition to acting as antidiuretic hormone is also considered to be stress hormone like hypothalamic corticotropin-releasing hormone (CRH). Present study was designed to investigate the relative response of these stress hormones during water and food deprivation. In this study, male laboratory mice of Swiss strain were divided in 5 groups, control - provided water and food ad libitum, two experimental groups water deprived for 2 and 4days respectively (WD2 and WD4) and another two groups food deprived for 2 and 4days respectively (FD2 and FD4). Results indicate an increased expression of AVP mRNA as well as peptide in the hypothalamus of WD2 mice and the expression was further upregulated after 4days of water deprivation but the expression of CRH remained unchanged compare to their respective controls. On the other hand no change was observed in the expression of hypothalamic AVP mRNA while AVP peptide increased significantly in FD2 and FD4 mice compare to control. Further, the expression of CRH mRNA although increased in hypothalamus of both FD2 and FD4 mice, the immunofluorescent staining shows decreased expression of CRH in PVN of food deprived mice. Based on these findings it is concluded that since during osmotic stress only AVP expression is upregulated but during metabolic stress i.e. food deprivation transcription and translation of both the stress hormones are differentially regulated. Further, it is suggested that role of AVP and CRH may be stress specific. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. CARDIOVASCULAR EFFECTS AND CHANGES IN MIDBRAIN PERIAQUEDUCTAL GRAY NEURONAL-ACTIVITY INDUCED BY ELECTRICAL-STIMULATION OF THE HYPOTHALAMUS IN THE RAT

    NARCIS (Netherlands)

    VANDERPLAS, J; WIERSINGAPOST, JEC; MAES, FW; BOHUS, B

    1995-01-01

    The effects of low-intensity electrical stimulation of sites in the hypothalamus and zona incerta (ZI) on mean blood pressure (MBP), heart rate (HR), and neuronal activity in the midbrain periaqueductal gray (FAG) were investigated in rats. Longlasting depressor responses were elicited from 67 sites

  14. Low dietary protein is associated with an increase in food intake and a decrease in the in vitro release of radiolabeled glutamate and GABA from the lateral hypothalamus.

    Science.gov (United States)

    White, B D; Du, F; Higginbotham, D A

    2003-12-01

    Moderately low-protein diets lead to a rapid increase in food intake and body fat. The increase in feeding is associated with a decrease in the concentration of serum urea nitrogen, suggesting that the low-protein-induced increase in food intake may be related to the decreased metabolism of nitrogen from amino acids. We hypothesized that low dietary protein would be associated with a decrease in the synaptic release of two nitrogen-containing neurotransmitters, GABA and glutamate, whose nitrogen can be derived from amino acids. In this study, we examined the effects of a low-protein diet (10% casein) in Sprague-Dawley rats on the in vitro release of 3H-GABA and 14C-glutamate from the lateral and medial hypothalamus. The low-protein diet increased food intake by about 25% after one day. After four days, the in vitro release of radiolabeled GABA and glutamate was assessed. The calcium-dependent, potassium-stimulated release of radiolabeled GABA and glutamate from the lateral hypothalamus was decreased in rats fed the low-protein diet. The magnitude of neurotransmitter release from the lateral hypothalamus inversely correlated with food intake. No dietary differences in the release of neurotransmitters from the medial hypothalamus were observed. These results support the contention that alterations in nitrogen metabolism are associated with low-protein-induced feeding.

  15. Noradrenaline concentration and turnover in nuclei of the hypothalamus and the medulla oblongata at two stages in the development of renal hypertension in the rat

    NARCIS (Netherlands)

    Wijnen, H.J.L.M.; Kloet, E.R. de; Versteeg, D.H.G.; Jong, Wybren de

    1980-01-01

    The noradrenaline concentration and the α-methyl-para-tyrosine (α-MPT)-induced disappearance of noradrenaline were determined in several nuclei of the hypothalamus and the medulla oblongata of renal hypertensive rats (two-kidney Goldblatt hypertension). A decreased α-MPT-induced disappearance of

  16. Differential effects of recombinant adeno-associated virus-mediated neuropeptide Y overexpression in the hypothalamic paraventricular nucleus and lateral hypothalamus on feeding behavior

    NARCIS (Netherlands)

    Tiesjema, Birgitte; Adan, Roger A. H.; Luijendijk, Mieneke C. M.; Kalsbeek, Andries; la Fleur, Susanne E.

    2007-01-01

    It is well known that neuropeptide Y (NPY) increases food intake. The hypothalamic paraventricular nucleus (PVN) and the lateral hypothalamus (LH) are both involved in the acute, hyperphagic effects of NPY. Although it is obvious that increased energy intake may lead to obesity, it is less

  17. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  18. Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

    NARCIS (Netherlands)

    Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.

    2011-01-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

  19. Biotin augments acetyl CoA carboxylase 2 gene expression in the hypothalamus, leading to the suppression of food intake in mice.

    Science.gov (United States)

    Sone, Hideyuki; Kamiyama, Shin; Higuchi, Mutsumi; Fujino, Kaho; Kubo, Shizuka; Miyazawa, Masami; Shirato, Saya; Hiroi, Yuka; Shiozawa, Kota

    2016-07-29

    It is known that biotin prevents the development of diabetes by increasing the functions of pancreatic beta-cells and improving insulin sensitivity in the periphery. However, its anti-obesity effects such as anorectic effects remain to be clarified. Acetyl CoA carboxylase (ACC), a biotin-dependent enzyme, has two isoforms (ACC1 and ACC2) and serves to catalyze the reaction of acetyl CoA to malonyl CoA. In the hypothalamus, ACC2 increases the production of malonyl CoA, which acts as a satiety signal. In this study, we investigated whether biotin increases the gene expression of ACC2 in the hypothalamus and suppresses food intake in mice administered excessive biotin. Food intake was significantly decreased by biotin, but plasma regulators of appetite, including glucose, ghrelin, and leptin, were not affected. On the other hand, biotin notably accumulated in the hypothalamus and enhanced ACC2 gene expression there, but it did not change the gene expression of ACC1, malonyl CoA decarboxylase (a malonyl CoA-degrading enzyme), and AMP-activated protein kinase α-2 (an ACC-inhibitory enzyme). These findings strongly suggest that biotin potentiates the suppression of appetite by upregulating ACC2 gene expression in the hypothalamus. This effect of biotin may contribute to the prevention of diabetes by biotin treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Effect of inhibitory avoidance trainning, ACTH, beta-endorphin and adrenaline on the incorporation of 14C-leucine into synaptosomal proteins of rat hypothalamus, amygdala and hippocampus

    International Nuclear Information System (INIS)

    Dalmaz, C.; Maia, H.M.M.; Izquierdo, I.

    1986-01-01

    'In vitro' incorporation of leucine to protein was studied in synaptosomes isolated from the hypothalamus, amygdala and hippocampus of rats submitted to inhibitory avoidance training or to the i.p. injection of ACTH, beta-endorphin or adrenaline; or in synaptosomes incubated with these substances. (M.A.C.) [pt

  1. Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: Development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain

    Science.gov (United States)

    Peng, Yu-Hao; Heintz, Ryan; Wang, Zhuo; Guo, Yumei; Myers, Kalisa; Scremin, Oscar; Maarek, Jean-Michel; Holschneider, Daniel

    2014-12-01

    Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex--changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic

  2. Omega 3 (peripheral type benzodiazepine binding) site distribution in the rat immune system: an autoradiographic study with the photoaffinity ligand [3H]PK 14105

    International Nuclear Information System (INIS)

    Benavides, J.; Dubois, A.; Dennis, T.; Hamel, E.; Scatton, B.

    1989-01-01

    The anatomical distribution of omega 3 (peripheral type benzodiazepine binding) sites in the immune system organs of the rat has been studied autoradiographically at both macroscopic and microscopic levels of resolution using either reversible or irreversible (UV irradiation) labeling with [ 3 H]PK 14105. In thymus sections, [ 3 H]PK 14105 labeled with high affinity (Kd, derived from saturation experiments = 10.8 nM) a single population of sites which possessed the pharmacological characteristics of omega 3 sites. In the thymus gland, higher omega 3 site densities were detected in the cortex than in the medulla; in these subregions, silver grains were associated to small (10-18 microns diameter) cells. In the spleen, omega 3 sites were more abundant in the white than in the red pulp. In the white pulp, silver grains were denser in the marginal zone than in the vicinity of the central artery and labeling was, as in the thymus, associated to small cytoplasm-poor cells. In the red pulp, omega 3 site associated silver grains were observed mainly in the Bilroth cords. In the lymph nodes, the medullary region showed a higher labeling than the surrounding follicles and paracortex. A significant accumulation of silver grains was observed in the lymph node medullary cords. In the intestine, Peyer patches were particularly enriched in omega 3 sites (especially in the periphery of the follicles). The distribution of omega 3 sites in the immune system organs suggests a preferential labeling of cells of T and monocytic lineages. This is consistent with the proposed immunoregulatory properties of some omega 3 site ligands

  3. Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329

    International Nuclear Information System (INIS)

    Hill, D.R.; Shaw, T.M.; Graham, W.; Woodruff, G.N.

    1990-01-01

    In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I-Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK-329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK-A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity

  4. Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated (2-D-penicillamine, 5-D-penicillamine)enkephalin ( sup 125 I-DPDPE)

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P.; Kalivas, P.W. (Washington State Univ., Pullman (USA))

    1990-01-01

    The enkephalin analog (2-D-penicillamine, 5-D-penicillamine)enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.

  5. Localization of gonadotropin binding sites in human ovarian neoplasms

    International Nuclear Information System (INIS)

    Nakano, R.; Kitayama, S.; Yamoto, M.; Shima, K.; Ooshima, A.

    1989-01-01

    The binding of human luteinizing hormone and human follicle-stimulating hormone to ovarian tumor biopsy specimens from 29 patients was analyzed. The binding sites for human luteinizing hormone were demonstrated in one tumor of epithelial origin (mucinous cystadenoma) and in one of sex cord-stromal origin (theca cell tumor). The binding sites for human follicle-stimulating hormone were found in three tumors of epithelial origin (serous cystadenoma and mucinous cystadenoma) and in two of sex cord-stromal origin (theca cell tumor and theca-granulosa cell tumor). The surface-binding autoradiographic study revealed that the binding sites for gonadotropins were localized in the stromal tissue. The results suggest that gonadotropic hormones may play a role in the growth and differentiation of a certain type of human ovarian neoplasms

  6. Neurotransmitter properties of the newborn human retina

    International Nuclear Information System (INIS)

    Hollyfield, J.G.; Frederick, J.M.; Rayborn, M.E.

    1983-01-01

    Human retinal tissue from a newborn was examined autoradiographically for the presence of high-affinity uptake and localization of the following putative neurotransmitters: dopamine, glycine, GABA, aspartate, and glutamate. In addition, the dopamine content of this newborn retina was measured by high pressure liquid chromatography. Our study reveals that specific uptake mechanisms for 3 H-glycine, 3 H-dopamine, and 3 H-GABA are present at birth. However, the number and distribution of cells labeled with each of these 3 H-transmitters are not identical to those observed in adult human retinas. Furthermore, the amount of endogenous dopamine in the newborn retina is approximately 1/20 the adult level. Photoreceptor-specific uptake of 3 H-glutamate and 3 H-aspartate are not observed. These findings indicate that, while some neurotransmitter-specific properties are present at birth, significant maturation of neurotransmitter systems occurs postnatally

  7. Autoradiography after incubation of tissue slices in 111 In-pentetreotide. Demonstration of the feasibility of the technique on rat brain slices. Application in two cases of human renal cell carcinoma

    International Nuclear Information System (INIS)

    Montravers, F.; Allard, S.; Fouret, P.; Daty, N.; Talbot, J.N.; Bernaudin, J.F.

    1996-01-01

    We report on a macroscopic autoradiographic technique using 111 In-pentetreotide after in vitro incubation of the slices. The feasibility of this technique has been demonstrated by the actual labeling of the deeper layers of the rat cerebral cortex, corresponding to the known cerebral distribution of somatostatin subtype 2 receptor. This technique has subsequently been applied in two of human renal cell carcinoma and has proven the presence of somatostatin receptors in both tumours. In one of these cases, a preoperative scintigraphy using 111 In-pentetreotide showed the absence of tumour visualization. The mechanism proposed to explain this discrepancy between scintigraphic and autoradiographic results is a lack of accessibility of the somatostatin analog to the receptor in case of voluminous renal tumour. (authors). 19 refs., 2 figs

  8. A molecular census of arcuate hypothalamus and median eminence cell types

    DEFF Research Database (Denmark)

    Campbell, John N; Macosko, Evan Z; Fenselau, Henning

    2017-01-01

    The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult...... mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a new leptin-sensing neuron population, multiple agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) subtypes, and an orexigenic...... somatostatin neuron population. We extended Drop-seq to detect dynamic expression changes across relevant physiological perturbations, revealing cell type-specific responses to energy status, including distinct responses in AgRP and POMC neuron subtypes. Finally, integrating our data with human genome...

  9. Kisspeptin Expression in Guinea Pig Hypothalamus: Effects of 17β-Estradiol

    Science.gov (United States)

    Bosch, Martha A.; Xue, Changhui; Rønnekleiv, Oline K.

    2013-01-01

    Kisspeptin is essential for reproductive functions in humans. As a model for the human we have used the female guinea pig, which has a long ovulatory cycle similar to that of primates. Initially, we cloned a guinea pig kisspeptin cDNA sequence and subsequently explored the distribution and 17β-estradiol (E2) regulation of kisspeptin mRNA (Kiss1) and protein (kisspeptin) by using in situ hybridization, real-time PCR and immunocytochemistry. In ovariectomized females, Kiss1 neurons were scattered throughout the preoptic periventricular areas (PV), but the vast majority of Kiss1 neurons were localized in the arcuate nucleus (Arc). An E2 treatment that first inhibits (negative feedback) and then augments (positive feedback) serum luteinizing hormone (LH) increased Kiss1 mRNA density and number of cells expressing Kiss1 in the PV at both time points. Within the Arc, Kiss1 mRNA density was reduced at both time points. Quantitative real-time PCR confirmed the in situ hybridization results during positive feedback. E2 reduced the number of immunoreactive kisspeptin cells in the PV at both time points, perhaps an indication of increased release. Within the Arc, the kisspeptin immunoreactivity was decreased during negative feedback but increased during positive feedback. Therefore, it appears that in guinea pig both the PV and the Arc kisspeptin neurons act cooperatively to excite gonadotropin-releasing hormone (GnRH) neurons during positive feedback. We conclude that E2 regulation of negative and positive feedback may reflect a complex interaction of the kisspeptin circuitry, and both the PV and the Arc respond to hormone signals to encode excitation of GnRH neurons during the ovulatory cycle. PMID:22173890

  10. Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model

    International Nuclear Information System (INIS)

    Saito, Y.; Rubenstein, R.; Price, R.W.; Fox, J.J.; Watanabe, K.A.

    1984-01-01

    To develop a new approach to the diagnosis of herpes simplex encephalitis, we used a radiolabeled antiviral drug, 2'-fluoro-5-methyl-1-beta-D-arabinosyluracil labeled with carbon 14 ([14C]FMAU), as a probe for selectively imaging brain infection in a rat model by quantitative autoradiography. A high correlation was found between focal infection, as defined by immunoperoxidase viral antigen staining, and increased regional [14C]FMAU uptake in brain sections. Two potential sources of false-positive imaging were defined: high concentrations of drug in the choroid plexus because of its higher permeability compared with brain, and drug sequestration by proliferating uninfected cell populations. Our results support the soundness of the proposed strategy of using a labeled antiviral drug that is selectively phosphorylated by herpes simplex virus type 1 thymidine kinase in conjunction with scanning methods for human diagnosis, and also define some of the factors that must be taken into account when planning clinical application

  11. Quantitative autoradiographic investigations on hairs, skin, and nails with the precursors 35S-cystine or 35S-methionine and 3H-thymidine respectively in animal experiments

    International Nuclear Information System (INIS)

    Schmiegelow, P.; Berndt, G.; Lindner, J.; Puschmann, M.

    1981-01-01

    By quantitative autoradiographic methods we tested the possible influence of the sulphurous amino acid L-cystine on the growth of hair, skin and nails. In the 3 H-thymidine autoradiographic method the tracing index (percentage of traced cell cores in relation to the total number of cell cores of a cell population) is calculated morphologically. In the 35 S-cystine and the 35 S-methionine autoradiography a quantification is carried out by applying the microscopic photometer for the investigation of defined hair root cross-sections. Measured values are indicated which depend on dosage and on the incorporation time. The investigation of other agents provoking negative or positive reactions of the hair growth by means of this method will have to be realized. Unlabelled L-cystine seems to promote the growth of hairs, epidermic basal cells and of germ cells of mouse nails, according to experiences made in animal experiments. The latter findings will have to be completed and confirmed by additional experiments. (orig.) [de

  12. Human brain imaging

    International Nuclear Information System (INIS)

    Kuhar, M.J.

    1987-01-01

    Just as there have been dramatic advances in the molecular biology of the human brain in recent years, there also have been remarkable advances in brain imaging. This paper reports on the development and broad application of microscopic imaging techniques which include the autoradiographic localization of receptors and the measurement of glucose utilization by autoradiography. These approaches provide great sensitivity and excellent anatomical resolution in exploring brain organization and function. The first noninvasive external imaging of receptor distributions in the living human brain was achieved by positron emission tomography (PET) scanning. Developments, techniques and applications continue to progress. Magnetic resonance imaging (MRI) is also becoming important. Its initial clinical applications were in examining the structure and anatomy of the brain. However, more recent uses, such as MRI spectroscopy, indicate the feasibility of exploring biochemical pathways in the brain, the metabolism of drugs in the brain, and also of examining some of these procedures at an anatomical resolution which is substantially greater than that obtainable by PET scanning. The issues will be discussed in greater detail

  13. Magnetic resonance imaging of hypothalamus hypophysis axis lesions; Relationship between posterior pituitary function and posterior bright spot

    Energy Technology Data Exchange (ETDEWEB)

    Shiina, Takeki; Uno, Kimiichi; Arimizu, Noboru; Yoshida, Sho (Chiba Univ. (Japan). School of Medicine); Yamada, Kenichi

    1990-04-01

    Magnetic resonance imaging (MRI) using a 0.5T superconductive machine was performed to the thirty three cases with a variety of the sellar and parasellar tumors and with dysfunction of the hypothalamus-hypophysis axis. Posterior pituitary bright spot (PBS) on T1 weighted image was evaluated with the pituitary hormonal function. These cases were 12 cases of post-treated tumors including pituitary adenoma (9 patients), suprasellar germinoma (2 patients) and craniopharyngioma (one patient), and non-tumorous conditions including 15 cases of central diabetes insipidus (DI), Syndrome of inappropriate secretion of ADH (SIADH) (one patient), Sheehan's syndrome (3 patients) and anorexia nervosa (2 patients). Pituitary bright spot was not seen in all 19 cases with overt DI. On the other hand, PBS was not seen in 9 cases without overt DI. Three cases of these 9 cases showing Sheehan's syndrome with insufficient antidiuretic hormone (ADH) secretion was considered as the state of subclinical DI. Posterior bright spot was not seen in all 13 cases of empty sella including partial empty sella. The results suggested that disappearance of PBS represents abnormality or loss of posterior pituitary function and also it was considered to be closely related to the empty sella. (author).

  14. Differential regulation of proopiomelanocortin (POMC mRNA expression in hypothalamus and anterior pituitary following repeated cyanamide with ethanol administration

    Directory of Open Access Journals (Sweden)

    Kinoshita Hiroshi

    2005-01-01

    Full Text Available Background/Aim. We have investigated proopiomelanocortin (POMC mRNA expression in the arcuate nucleus of the hypothalamus (ARC and the anterior lobe of the pituitary (AL following repeated cyanamide-ethanol reaction (CER. Methods. Adult male Sprague -Dawley rats (250 −290 gr were housed in a temperature and humidity controlled environment with free access to food and water. Four experimental groups were used as follows: saline (as control, cyanamide alone, ethanol alone and ethanol with cyanamide. The animals received daily intraperitoneal injections (i.p. of cyanamide (10mg/kg, 60 min before ethanol dosing with or without ethanol (1g/kg for 5 consecutive days, and were sacrificed 60 min after the last dosing of ethanol. The results were presented as the mean ± SEM for each group. All groups within each data set were compared by one-way ANOVA followed by Fisher PLSD test for multiple comparisons. A value of p<0.05 was considered significant. Results. The POMC mRNA levels in ARC were significantly decreased with cyanamide compared to the control and ethanol alone (p<0.05 and p<0.05 respectively, but increased in AL following repeated CER. Conclusion. We speculate that this differential regulation of POMC mRNA expression may be partially involved in the preventive effects on alcohol intake in response to CER.

  15. Glutamate AMPA/kainate receptors, not GABA(A) receptors, mediate estradiol-induced sex differences in the hypothalamus.

    Science.gov (United States)

    Todd, Brigitte J; Schwarz, Jaclyn M; Mong, Jessica A; McCarthy, Margaret M

    2007-02-15

    Sex differences in brain morphology underlie physiological and behavioral differences between males and females. During the critical perinatal period for sexual differentiation in the rat, gonadal steroids act in a regionally specific manner to alter neuronal morphology. Using Golgi-Cox impregnation, we examined several parameters of neuronal morphology in postnatal day 2 (PN2) rats. We found that in the ventromedial nucleus of the hypothalamus (VMN) and in areas just dorsal and just lateral to the VMN that there was a sex difference in total dendritic spine number (males greater) that was abolished by treating female neonates with exogenous testosterone. Dendritic branching was similarly sexually differentiated and hormonally modulated in the VMN and dorsal to the VMN. We then used spinophilin, a protein that positively correlates with the amount of dendritic spines, to investigate the mechanisms underlying these sex differences. Estradiol, which mediates most aspects of masculinization and is the aromatized product of testosterone, increased spinophilin levels in female PN2 rats to that of males. Muscimol, an agonist at GABA(A) receptors, did not affect spinophilin protein levels in either male or female neonates. Kainic acid, an agonist at glutamatergic AMPA/kainate receptors, mimicked the effect of estradiol in females. Antagonizing AMPA/kainate receptors with NBQX prevented the estradiol-induced increase in spinophilin in females but did not affect spinophilin level in males. (c) 2007 Wiley Periodicals, Inc.

  16. An Estrogen-Responsive Module in the Ventromedial Hypothalamus Selectively Drives Sex-Specific Activity in Females

    Directory of Open Access Journals (Sweden)

    Stephanie M. Correa

    2015-01-01

    Full Text Available Estrogen-receptor alpha (ERα neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1+ VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα+ neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

  17. Microstructure alterations in the hypothalamus in cranially radiated childhood leukaemia survivors but not in craniopharyngioma patients unaffected by hypothalamic damage.

    Science.gov (United States)

    Follin, Cecilia; Fjalldal, Sigridur; Svärd, Daniel; van Westen, Danielle; Gabery, Sanaz; Petersén, Åsa; Lätt, Jimmy; Rylander, Lars; Erfurth, Eva Marie

    2017-10-01

    Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors. Case-control study. Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls. DTI parameters of the HT were measured and body composition. Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls. Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT. © 2017 John Wiley & Sons Ltd.

  18. The hypothalamus-pituitary-thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

    Science.gov (United States)

    Carr, J.A.; Patino, R.

    2011-01-01

    Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health. ?? 2010 Elsevier Inc.

  19. Leucine deprivation stimulates fat loss via increasing CRH expression in the hypothalamus and activating the sympathetic nervous system.

    Science.gov (United States)

    Cheng, Ying; Zhang, Qian; Meng, Qingshu; Xia, Tingting; Huang, Zhiying; Wang, Chunxia; Liu, Bin; Chen, Shanghai; Xiao, Fei; Du, Ying; Guo, Feifan

    2011-09-01

    We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three β-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis.

  20. Na+ pump in renal tubular cells is regulated by endogenous Na+-K+-ATPase inhibitor from hypothalamus

    International Nuclear Information System (INIS)

    Cantiello, H.F.; Chen, E.; Ray, S.; Haupert, G.T. Jr.

    1988-01-01

    Bovine hypothalamus contains a high affinity, specific, reversible inhibitor of mammalian Na + -K + -ATPase. Kinetic analysis using isolated membrane fractions showed binding and dissociation rates of the hypothalamic factor (HF) to be (like ouabain) relatively long (off rate = 60 min). To determine whether the kinetics of inhibition in intact cells might be more consistent with regulation of physiological processes in vivo, binding and dissociation reactions of HF in intact renal epithelial cells (LLC-PK 1 ) were studied using 86 Rb + uptake and [ 3 H]ouabain binding. As with membranes, a 60-min incubation with HF inhibited Na + -K + -ATPase in LLC-PK 1 cells. In contrast to membrane studies, no prolonged incubation with LLC-PK 1 was needed to observe inhibition of Na + -K + -ATPase. HF caused a 33% inhibition of ouabain-sensitive 86 Rb + influx within 10 min. Incubation of cells with HF followed by washout showed rapid reversal of pump inhibition and a doubling of pump activity. The dose-response curve for HF inhibition of LLC-PK 1 86 Rb + uptake showed a sigmoidal shape consistent with an allosteric binding reaction. Thus HF is a potent regulator of Na + -K + -ATPase activity in intact renal cells, with binding and dissociation reactions consistent with relevant physiological processes