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- Broberger, C, et al.
(författare)
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Neuropeptide Y innervation and neuropeptide-Y-Y1-receptor-expressing neurons in the paraventricular hypothalamic nucleus of the mouse
- 1999
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 70:5, s. 295-305
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Tidskriftsartikel (refereegranskat)abstract
- The paraventricular hypothalamic nucleus (PVH) serves as integrator and link between the neuroendocrine and autonomic nervous systems. Neuropeptide-Y (NPY)-producing neurons in the arcuate nucleus project to the PVH, where neurons expressing NPY Y1 receptor (Y1R) have been demonstrated. This projection has been suggested to be involved in the regulation of parameters related to energy metabolism, e.g. food intake and thermoregulation. The present study aimed at characterizing this pathway and chemically defining Y1R-expressing neurons by means of immunohistochemistry. The densely distributed NPY-immunoreactive (ir) terminals in the PVH co-stained for agouti gene-related protein (AGRP) mainly in the medial parvocellular regions, indicating an origin in the arcuate nucleus. This was in contrast to noradrenergic/adrenergic terminals in the PVH, which were less frequently seen to contain NPY-like immunoreactivity. Furthermore, AGRP-ir terminals were seen forming abundant close appositions on Y1R-ir cell bodies. Double staining revealed co-existence of Y1R-like immunoreactivity and immunoreactivities for thyrotropin-releasing hormone (TRH) and, to a minor extent, cocaine- and amphetamine-regulated transcript peptide in parvocellular neurons. No Y1R-like immunoreactivity was noted in parvocellular neurons expressing corticotropin-releasing hormone or in magnocellular neurons expressing vasopressin or oxytocin. The present results suggest that the arcuatoparaventricular NPY projection targets the TRH neurons preferentially via the Y1R, whereas the NPYergic regulation of corticotropinergic and magnocellular neurons may be relayed through other subtypes of NPY receptors. This study further defines the link between NPY-induced feeding and the hypothalamus-pituitary-thyroid axis.
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- Calza, L, et al.
(författare)
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Thyroid hormone-dependent regulation of galanin synthesis in neurons and glial cells after colchicine administration
- 1998
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 68:6, s. 428-436
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Tidskriftsartikel (refereegranskat)abstract
- Galanin and galanin message-associated peptide (GMAP) synthesis is up-regulated in neurons and glial cells in the adult rat brain by different experimental manipulations, including intracerebroventricular colchicine. We have previously reported that the galanin expression is severely attenuated in some neurons in adult hypothyroidism. In order to further investigate the role of thyroid hormone for the in vivo regulation of galanin gene expression, we have studied the effect of intraventricular administration of colchicine on prepro-galanin (ppGAL) mRNA expression in the brain of normal and hypothyroid, adult male rats. While ppGAL mRNA levels were markedly elevated in a great number of glial cells in the white and gray matter in normal rats, this effect was almost completely abolished in hypothyroid rats. In contrast, colchicine-induced up-regulation of galanin/GMAP expression occurs in the hypothalamic paraventricular nucleus both of euthyroid and hypothyroid rats, although with a slightly different time course.
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- Hakansson, ML, et al.
(författare)
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Transcription factor STAT3 in leptin target neurons of the rat hypothalamus
- 1998
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 68:6, s. 420-427
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipose tissue-derived hormone that regulates body weight via interactions with hypothalamic neuronal circuitries expressing specific leptin receptors (Ob-R). The Ob-Rs act via the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway of signal transduction. Recent evidence suggests that primarily the transcription factor STAT3 mediates leptin’s action in the hypothalamus. We have investigated the presence and cellular localization of STAT3 protein in the rat hypothalamus by means of indirect immunofluorescence histochemistry using a rabbit polyclonal STAT3 antiserum. The antiserum identified a 92-kDa protein using Western blotting on rat hypothalamic homogenates, corresponding to the expected size of STAT3. STAT3 immunoreactivity was demonstrated in Ob-R-containing neurons of the paraventricular nucleus (parvocellular part), periventricular nucleus, arcuate nucleus and in the lateral hypothalamic area. Direct double-labeling showed presence of STAT3 immunoreactivity in neuropeptide Y (NPY)-containing neurons of the ventromedial part of the arcuate nucleus and in proopiomelanocortin (POMC)-containing neurons of the ventrolateral part of the arcuate nucleus. The results provide an anatomical basis for a leptin action mediated by STAT3 in Ob-R-containing NPY and POMC neurons of the arcuate nucleus, as well as by Ob-R-containing neurons of the parvocellular paraventricular nucleus and lateral hypothalamic area.
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- Jacobsson, G, et al.
(författare)
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Isoform-specific exocytotic protein mRNA expression in hypothalamic magnocellular neurons: regulation after osmotic challenge
- 1999
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 70:6, s. 392-401
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Tidskriftsartikel (refereegranskat)abstract
- Exocytosis is regulated by proteins which interact to promote docking and fusion of secretory granules with the plasma membrane. We have used in situ hybridization to study the mRNA expression for <i>v</i>esicle-<i>a</i>ssociated <i>m</i>embrane <i>p</i>rotein (VAMP) isoforms VAMP-1 and VAMP-2, <i>s</i>ynaptosomal-<i>a</i>ssociated <i>p</i>rotein of 25-kDa (SNAP-25) isoforms SNAP-25a and SNAP-25b, <i>m</i>ammalian homologue of <i>unc</i>-18 (munc-18) and Hrs-2 in neurosecretory neurons of the magnocellular paraventricular (PVN) and supraoptic (SON) nuclei of normal and osmotically challenged animals. In PVN and SON neurons of normal animals, strong labeling was demonstrated for VAMP-2 and SNAP-25a mRNA, whereas VAMP-1 or SNAP-25b mRNA could not be detected. Salt-loading (2% NaCl as drinking water), an animal model which increases the expression and secretion of hormones from hypothalamic magnocellular neurons, resulted in significantly increased mRNA levels for VAMP-2 (36%, 28%), munc-18 (74%, 68%) and SNAP-25a (59%, 77%) in the PVN and SON, respectively. There was no significant increase in Hrs-2 mRNA levels in the PVN, whereas a significant increase (22%) was observed in the SON. In the posterior pituitary, immunohistochemistry showed a marked decrease in numbers and intensity of vasopressin-immunoreactive (-IR) nerve endings after salt-loading. There were no obvious changes in numbers or intensity of VAMP-2-, munc-18-, Hrs-2- or SNAP-25-IR fibers. Large varicosities containing VAMP-2- and Hrs-2 immunocreactivity were seen in salt-loaded animals. The results show isoform-specific mRNA expression in neurosecretory neurons and an increased mRNA expression of proteins participating in the molecular regulation of exocytosis during an experimental situation characterized by increased secretion.
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- Petersson, M, et al.
(författare)
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Long-term changes in gastrin, cholecystokinin and insulin in response to oxytocin treatment
- 1999
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 69:3, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- The present study was designed to investigate how repeated injections of oxytocin influence plasma levels of vagally controlled hormones such as gastrin, cholecystokinin (CCK), insulin and somatostatin, as well as of endogenous oxytocin and glucose. Since oxytocin may enhance the activity of centrally located α<sub>2</sub>-adrenoreceptors, a second aim of this study was to explore whether these receptors are involved in the effects. For this purpose, oxytocin (1.0 mg/kg) or NaCl was given subcutaneously (s.c.) once a day during 5 days to male rats. Rats were decapitated 1, 3 and 10 days after the last injection, blood was collected and hormone levels were radioimmunoassayed. The oxytocin treatment caused an elevation of plasma levels of oxytocin 1 day (p < 0.05) but not 3 and 10 days after treatment. Gastrin levels were decreased on day 1, 3 and 10 (ANOVA; p < 0.01). In addition, both insulin and CCK levels were decreased in response to the oxytocin treatment when measured 3 and 10 days after the last injection (ANOVA; insulin p < 0.01, CCK p < 0.05). When the α<sub>2</sub>-adrenoreceptor agonist clonidine (2.5 µg/kg intracerebroventricularly) was administered 3 days after the 5-day treatment period with oxytocin or saline, plasma levels of insulin and CCK increased significantly (p < 0.05) in the oxytocin-treated rats, when compared to saline-treated controls receiving clonidine only. No change in glucose or somatostatin levels was found in response to the oxytocin treatment. In conclusion, these results show that oxytocin induces long-lasting changes in plasma levels of gastrin, CCK and insulin, without affecting somatostatin or glucose levels. These effects may be mediated by changes in vagal nerve activity.
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