Download PDF
Horm Metab Res 2001; 33(9): 525-531
DOI: 10.1055/s-2001-17210
Original Basic

© Georg Thieme Verlag Stuttgart · New York

Distribution of 1,25-Dihydroxyvitamin D3 Receptor Immunoreactivity in the Limbic System of the Rat

T. Walbert 1 , G. F. Jirikowski 1 , K. Prüfer 1, 2
  • 1 Institut für Anatomie/Anatomie II, Friedrich-Schiller Universität Jena, Germany
  • 2 NIH, NIDDK, LCBB, Bethesda, MD, USA
Further Information

Publication History

Publication Date:
17 September 2001 (online)

Also available at
    Permissions and Reprints

We used immunocytochemistry to obtain a complete cellular and subcellular mapping of the 1,25-dihydroxyvitamin D3 receptor protein (VDR) in the rat limbic system. We observed specific VDR immunostaining in the nucleus as well as in the perinuclear cytoplasm of neuronal cells. The limbic system consists of a variety of neuronal structures, and is known to have influence on memory, behavior, emotions and reproduction. In the hippocampal formation, we found strong nuclear staining as well as less distinguished cytoplasmic VDR staining in CA1, CA3 and CA4. The CA2 area showed a unique cytoplasmic predominance of VDR. The amygdala was found to exhibit specific patterns of VDR distribution in the various regions of the nucleus. We observed distinct differences of VDR localization within the limbic preoptic areas of the hypothalamus. Further parts of the brain we analyzed included the mammillary bodies, the indusium griseum and the cingulate cortex. The subcellular distribution of VDR in regions of the limbic system suggests a specific functional role of the receptor protein and indicates a role for calcitriol as a neuroactive steroid.

Key words:

 Steroid - 1,25-Dihydroxyvitamin D3 - Limbic System - Rat - Vitamin D Receptor

References

  • 1 Ayer-LeLievre C, Olson L, Ebendal T, Seiger A, Persson H. Expression of the beta-nerve growth factor gene in hippocampal neurons.  Science. 1988;  240 1339-1341
    PubMedGoogle Scholar
  • 2 Barsony J, Renyi I, McKoy W. Subcellular distribution of normal and mutant vitamin D receptors in living cells. Studies with a novel fluorescent ligand.  J Biol Chem. 1997;  272 5774-5782
    CrossrefPubMedGoogle Scholar
  • 3 Bechara A, Tranel D, Damasio H, Adolphs R, Rockland C, Damasio A R. Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans.  Science. 1995;  269 1115-1118
    CrossrefPubMedGoogle Scholar
  • 4 Berger U. Immunocytochemical detection of 1,25-dihydroxyvitamin D3 receptors in normal human tissues.  J Clin Endocrinol Metab. 1988;  67 607-613
    CrossrefPubMedGoogle Scholar
  • 5 Bidmon H J, Stumpf W E. Distribution of target cells for 1,25-dihydroxyvitamin D3 in the brain of the yellow bellied turtle trachemys scripta.  Brain Res. 1994;  640 277-285
    CrossrefPubMedGoogle Scholar
  • 6 Bidmon H J, Stumpf W E. Vitamin D target systems in the brain of the green lizard Anolis carolinensis.  Anat Embryol (Berlin). 1996;  193 145-160
    PubMedGoogle Scholar
  • 7 Clemens T L, Garrett K P, Zhou X Y, Pike J W, Haussler M R, Dempster D W. Immunocytochemical localization of the 1,25-dihydroxyvitamin D3 receptor in target cells.  Endocrinology. 1988;  122 1224-1230
    PubMedGoogle Scholar
  • 8 DeLuca H F. The vitamin D story: a collaborative effort of basic science and clinical medicine.  FASEB J . 1988;  2 224-236
    PubMedGoogle Scholar
  • 9 Doebler J A, Markesbery W R, Anthony A, Rhoads R E. Neuronal RNA in relation to neuronal loss and neurofibrillary pathology in the hippocampus in Alzheimer's disease.  J Neuropathol Exp Neurol. 1987;  46 28-39
    PubMedGoogle Scholar
  • 10 Glaser S D, Veenstra T D, Jirikowski G F, Prüfer K. Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the rat olfactory system.  Cell Mol Neurobiol. 1999;  19 613-624
    CrossrefPubMedGoogle Scholar
  • 11 Jirikowski G F, Celeda D, Jantz M, Prufer K, Lee J S. Sense- and antisense-targeting of oxytocinergic systems in the rat hypothalamus. In: Oxytocin, cellular and molecular approaches in medicine and research.  Adv Exp Med Biol. 1995;  395 59-65
    PubMedGoogle Scholar
  • 12 Johnson J A, Grande J P, Roche P C, Sweeney W E Jr, Avner E D, Kumar R. 1 alpha, 25-dihydroxyvitamin D3 receptor ontogenesis in fetal renal development.  Am J Physiol. 1995;  269 F419-F428
    PubMedGoogle Scholar
  • 13 Johnson J A, Grande J P, Windebank A J, Kumar R. 1,25-Dihydroxyvitamin D(3) receptors in developing dorsal root ganglia of fetal rats.  Brain Res Dev Brain Res. 1996;  92 120-124
    PubMedGoogle Scholar
  • 14 Keddie K M. Severe depressive illness in the context of hypervitaminosis D.  Br J Psychiatry. 1987;  150 394-396
    PubMedGoogle Scholar
  • 15 Kumar R. Metabolism of 1,25-dihydroxyvitamin D3.  Physiol Rev. 1984;  64 478-504
    PubMedGoogle Scholar
  • 16 Kumar R, Schaefer J, Wieben E. The expression of milligram amounts of functional human 1,25- dihydroxyvitamin D3 receptor in a bacterial expression system.  Biochem Biophys Res Commun. 1992;  189 1417-1423
    CrossrefPubMedGoogle Scholar
  • 17 Lansdowne A T, Provost S C. Vitamin D3 enhances mood in healthy subjects during winter.  Psychopharmacology. 1998;  135 319-323
    CrossrefPubMedGoogle Scholar
  • 18 MacLean P D. Psychosomatic disease and the “visceral brain”: Recent developments bearing on the Papez theory of emotion.  Psychosom Med. 1949;  11 338-353
    PubMedGoogle Scholar
  • 19 Mirzahosseini S, Karabelyos C, Dobozy O, Csaba G. Changes in sexual behavior of adult male and female rats neonatally treated with vitamin D3.  Hum Exp Toxicol. 1996;  15 573-576
    PubMedGoogle Scholar
  • 20 Musiol I M, Feldman D. 1,25-dihydroxyvitamin D3 induction of nerve growth factor in L929 mouse fibroblasts: effect of vitamin D receptor regulation and potency of vitamin D3 analogs.  Endocrinology. 1997;  138 12-18
    CrossrefPubMedGoogle Scholar
  • 21 Musiol I M, Stumpf W E, Bidmon H J, Heiss C, Mayerhofer A, Bartke A. Vitamin D nuclear binding to neurons of the septal, substriatal and amygdaloid area in the Siberian hamster (Phodopus sungorus) brain.  Neuroscience. 1992;  48 841-848
    CrossrefPubMedGoogle Scholar
  • 22 Neveu I, Naveilhan P, Jehan F, Baudet C, Wion D, De Luca H F, Brachet P. 1,25-Dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells.  Mol Brain Res. 1994;  24 70-76
    CrossrefPubMedGoogle Scholar
  • 23 Olson L. NGF and the treatment of Alzheimer's disease.  Exp Neurol. 1993;  124 5-15
    CrossrefPubMedGoogle Scholar
  • 24 Papez J W. A proposed mechanism of emotion.  Arch Neurol Psychiatry. 1937;  38 725-743
    PubMedGoogle Scholar
  • 25 Paxinos G, Watson C. The rat brain in stereotaxic coordinates.  San Diego/USA:; Academic Press, 1997 3rd compact edition
    Google Scholar
  • 26 Prüfer K, Jirikowski G F. 1.25-Dihydroxyvitamin D3 receptor is partly colocalized with oxytocin immunoreactivity in neurons of the male rat hypothalamus.  Cell Mol Biol. 1997;  43 543-548
    PubMedGoogle Scholar
  • 27 Prüfer K, Veenstra T D, Jirikowski G F, Kumar R. Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the rat brain and spinal cord.  J Chem Neuroanat. 1999;  16 135-145
    CrossrefPubMedGoogle Scholar
  • 28 Racz A, Barsony J. Hormone-dependent translocation of vitamin D receptors is linked to transactivation.  J Biol Chem. 1999;  274 19 352-19 360
    PubMedGoogle Scholar
  • 29 Reichrath J, Collins E D, Epple S, Kerber A, Norman A W, Bahmer F A. Immunohistochemical detection of 1,25-dihydroxyvitamin D3 receptors (VDR) in human skin. A comparison of five antibodies.  Pathol Res Pract. 1996;  192 281-289
    PubMedGoogle Scholar
  • 30 Saporito M S, Brown E R, Hartpence K C, Wilcox H M, Vaught J L, Carswell S. Chronic 1,25-dihydroxyvitamin D3-mediated induction of nerve growth factor mRNA and protein in L929 fibroblasts and in adult rat brain.  Brain Res. 1994;  633 189-196
    CrossrefPubMedGoogle Scholar
  • 31 Saporito M S, Wilcox H M, Hartpence K C, Lewis M E, Vaught J L, Carswell S. Pharmacological induction of nerve growth factor mRNA in adult rat brain.  Exp Neurol. 1993;  123 295-302
    CrossrefPubMedGoogle Scholar
  • 32 Sonnenberg J, Luine V N, Krey L C, Christakos S. 1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei.  Endocrinology. 1986;  118 1433-1439
    PubMedGoogle Scholar
  • 33 Stumpf W E. Vitamin D sites and mechanisms of action: a histochemical perspective. Reflections on the utility of autoradiography and cytopharmacology for drug targeting.  Histochem Cell Biol. 1995;  104 417-427
    CrossrefPubMedGoogle Scholar
  • 34 Stumpf W E, Bidmon H J, Li L, Pilgrim C, Bartke A, Mayerhofer A, Heiss C. Nuclear receptor sites for vitamin D-soltriol in midbrain and hindbrain of Siberian hamster (Phodopus sungorus) assessed by autoradiography.  Histochemistry. 1992;  98 155-164
    CrossrefPubMedGoogle Scholar
  • 35 Stumpf W E, Privette T H. Light, vitamin D and psychiatry. Role of 1,25 dihydroxyvitamin D3 (soltriol) in etiology and therapy of seasonal affective disorder and other mental processes.  Psychopharmacology. 1989;  97 285-294
    CrossrefPubMedGoogle Scholar
  • 36 Sutherland R J. Configural association theory: The role of the hippocampal formation in learning, memory, and amnesia.  Psychobiology. 1989;  17 129-144
    PubMedGoogle Scholar
  • 37 Sutherland M K, Somerville M J, Yoong L K, Bergeron C, Haussler M R, McLachlan D R. Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: correlation with calbindin-28k mRNA levels.  Brain Res Mol Brain Res. 1992;  13 239-250
    CrossrefPubMedGoogle Scholar
  • 38 Veenstra T D, Londowski J M, Windebank A J, Brimijoin S, Kumar R. Effects of 1,25-dihydroxyvitamin D3 on growth of mouse neuroblastoma cells.  Dev Brain Res. 1997;  99 53-60
    CrossrefPubMedGoogle Scholar
  • 39 Walters M R. Newly identified actions of the vitamin D endocrine system.  Endocr Rev. 1992;  13 719-764
    CrossrefPubMedGoogle Scholar
  • 40 Walters M R, Fischette C T, Fetzer C, May B, Riggle P C, Tibaldo-Bongiorno M, Christakos S. Specific 1,25-dihydroxyvitamin D3 binding sites in choroid plexus.  Eur J Pharmacol. 1992;  213 309-311
    CrossrefPubMedGoogle Scholar
  • 41 Wion D, MacGrogan D, Neveu I, Jehan F, Houlgatte R, Brachet P. 1,25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis.  J Neurosci Res. 1991;  28 110-114
    CrossrefPubMedGoogle Scholar

Prof. Dr. G. Jirikowski

Institut für Anatomie ll
Klinikum der FSU

Teichgraben 7
07743 Jena
Germany


Phone: + 49 (3641) 938553

Fax: + 49 (3641) 938552

Email: gjir@mti.n.mti.uni-jena.de

      >