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
-
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
-
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
-
4
Berger U.
Immunocytochemical detection of 1,25-dihydroxyvitamin D3 receptors in normal human tissues.
J Clin Endocrinol Metab.
1988;
67
607-613
-
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
-
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
-
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
-
8
DeLuca H F.
The vitamin D story: a collaborative effort of basic science and clinical medicine.
FASEB J .
1988;
2
224-236
-
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
-
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
-
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
-
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
-
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
-
14
Keddie K M.
Severe depressive illness in the context of hypervitaminosis D.
Br J Psychiatry.
1987;
150
394-396
-
15
Kumar R.
Metabolism of 1,25-dihydroxyvitamin D3.
Physiol Rev.
1984;
64
478-504
-
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
-
17
Lansdowne A T, Provost S C.
Vitamin D3 enhances mood in healthy subjects during winter.
Psychopharmacology.
1998;
135
319-323
-
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
-
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
-
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
-
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
-
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
-
23
Olson L.
NGF and the treatment of Alzheimer's disease.
Exp Neurol.
1993;
124
5-15
-
24
Papez J W.
A proposed mechanism of emotion.
Arch Neurol Psychiatry.
1937;
38
725-743
-
25 Paxinos G, Watson C. The rat brain in stereotaxic coordinates. San Diego/USA:; Academic Press, 1997 3rd compact edition
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
36
Sutherland R J.
Configural association theory: The role of the hippocampal formation in learning, memory, and amnesia.
Psychobiology.
1989;
17
129-144
-
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
-
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
-
39
Walters M R.
Newly identified actions of the vitamin D endocrine system.
Endocr Rev.
1992;
13
719-764
-
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
-
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
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
