Expression Profiles of the Nuclear Receptors and Their Transcriptional Coregulators During Differentiation of Neural Stem Cells

A. Androutsellis-Theotokis; G. P. Chrousos; R. D. McKay; A. H. DeCherney; T. Kino

doi:10.1055/s-0032-1321789

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2013; 45(02): 159-168
DOI: 10.1055/s-0032-1321789

Original Basic

Expression Profiles of the Nuclear Receptors and Their Transcriptional Coregulators During Differentiation of Neural Stem Cells

A. Androutsellis-Theotokis

¹Department of Medicine, University of Dresden and Center for Regenerative Therapies-Dresden, Dresden, Germany

,

G. P. Chrousos

²First Department of Pediatrics, Athens University Medical School, Athens, Greece

,

R. D. McKay

³Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

,

A. H. DeCherney

⁴Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

,

T. Kino

⁴Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

› Institutsangaben

Abstract

Neural stem cells (NSCs) are pluripotent precursors with the ability to proliferate and differentiate into 3 neural cell lineages, neurons, astrocytes and oligodendrocytes. Elucidation of the mechanisms underlying these biologic processes is essential for understanding both physiologic and pathologic neural development and regeneration after injury. Nuclear hormone receptors (NRs) and their transcriptional coregulators also play crucial roles in neural development, functions and fate. To identify key NRs and their transcriptional regulators in NSC differentiation, we examined mRNA expression of 49 NRs and many of their coregulators during differentiation (0–5 days) of mouse embryonic NSCs induced by withdrawal of fibroblast growth factor-2 (FGF2). 37 out of 49 NRs were expressed in NSCs before induction of differentiation, while receptors known to play major roles in neural development, such as THRα, RXRs, RORs, TRs, and COUP-TFs, were highly expressed. CAR, which plays important roles in xenobiotic metabolism, was also highly expressed. FGF2 withdrawal induced mRNA expression of RORγ, RXRγ, and MR by over 20-fold. Most of the transcriptional coregulators examined were expressed basally and throughout differentiation without major changes, while FGF2 withdrawal strongly induced mRNA expression of several histone deacetylases (HDACs), including HDAC11. Dexamethasone and aldosterone, respectively a synthetic glucocorticoid and natural mineralocorticoid, increased NSC numbers and induced differentiation into neurons and astrocytes. These results indicate that the NRs and their coregulators are present and/or change their expression during NSC differentiation, suggesting that they may influence development of the central nervous system in the absence or presence of their ligands.

Key words

central nervous system - histone deacetylase - glucocorticoid - mineralocorticoid - neuron

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References
1 Burris TP. The nuclear receptor superfamily. In: Burris TP, McCabe ERB. (eds.) Nuclear receptors and genetic disease. London: Academic Press; 2001: 1-58
2 Horn S, Heuer H. Thyroid hormone action during brain development: More questions than answers. Mol Cell Endocrinol 2010; 315: 19-26
3 Wolkowitz OM, Burke H, Epel ES, Reus VI. Glucocorticoids. Mood, memory, and mechanisms. Ann N Y Acad Sci 2009; 1179: 19-40
4 Hughes ZA, Liu F, Marquis K, Muniz L, Pangalos MN, Ring RH, Whiteside GT, Brandon NJ. Estrogen receptor neurobiology and its potential for translation into broad spectrum therapeutics for CNS disorders. Curr Mol Pharmacol 2009; 2: 215-236
5 Kino T, Chrousos GP. Glucocorticoid effect on gene expression. In: Steckler T, Kalin NH, Reul JMHM. eds. Handbook on Stress and the Brain. Amsterdam: Elsevier BV; 2005: 295-312
6 McKenna NJ, Lanz RB, O’Malley BW. Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 1999; 20: 321-344
7 Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal 2010; 3: ra8
8 Androutsellis-Theotokis A, Murase S, Boyd JD, Park DM, Hoeppner DJ, Ravin R, McKay RD. Generating neurons from stem cells. Methods Mol Biol 2008; 438: 31-38
9 Androutsellis-Theotokis A, Rueger MA, Park DM, Mkhikian H, Korb E, Poser SW, Walbridge S, Munasinghe J, Koretsky AP, Lonser RR, McKay RD. Targeting neural precursors in the adult brain rescues injured dopamine neurons. Proc Natl Acad Sci USA 2009; 106: 13570-13575
10 Androutsellis-Theotokis A, Rubin de Celis MF, Ehrhart-Bornstein M, Bornstein SR. Common features between chromaffin and neural progenitor cells. Mol Psychiatry 2012; 17: 351
11 Bornstein SR, Ehrhart-Bornstein M, Androutsellis-Theotokis A, Eisenhofer G, Vukicevic V, Licinio J, Wong ML, Calissano P, Nistico G, Preziosi P, Levi-Montalcini R. Chromaffin cells: the peripheral brain. Mol Psychiatry 2012; 17: 354-358
12 Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD. Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 2006; 442: 823-826
13 Androutsellis-Theotokis A, Rueger MA, Mkhikian H, Korb E, McKay RD. Signaling pathways controlling neural stem cells slow progressive brain disease. Cold Spring Harb Symp Quant Biol 2008; 73: 403-410
14 Kittappa R, Bornstein SR, Androutsellis-Theotokis A. The role of eNSCs in neurodegenerative disease. Mol Neurobiol 2012; in press
15 Ng SS, Chang TH, Tailor P, Ozato K, Kino T. Virus-induced differential expression of nuclear receptors and coregulators in dendritic cells: Implication to interferon production. FEBS Lett 2011; 585: 1331-1337
16 Kino T, Ichijo T, Amin ND, Kesavapany S, Wang Y, Kim N, Rao S, Player A, Zheng YL, Garabedian MJ, Kawasaki E, Pant HC, Chrousos GP. Cyclin-dependent kinase 5 differentially regulates the transcriptional activity of the glucocorticoid receptor through phosphorylation: Clinical Implications for the nervous system response to glucocorticoids and stress. Mol Endocrinol 2007; 21: 1552-1568
17 van Neerven S, Kampmann E, Mey J. RAR/RXR and PPAR/RXR signaling in neurological and psychiatric diseases. Prog Neurobiol 2008; 85: 433-451
18 Pereira FA, Qiu Y, Tsai MJ, Tsai SY. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) expression during mouse embryogenesis. J Steroid Biochem Mol Biol 1995; 53: 503-508
19 Levesque D, Rouillard C. Nur77 and retinoid X receptors: Crucial factors in dopamine-related neuroadaptation. Trends Neurosci 2007; 30: 22-30
20 Hall MG, Quignodon L, Desvergne B. Peroxisome proliferator-activated receptor β/δ in the brain: Facts and hypothesis. PPAR Res 2008; 2008: 780452
21 Lee YF, Lee HJ, Chang C. Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily. J Steroid Biochem Mol Biol 2002; 81: 291-308
22 Schnegg CI, Robbins ME. Neuroprotective mechanisms of PPARδ: Modulation of oxidative stress and inflammatory processes. PPAR Res 2011; 2011: 373560
23 Real MA, Heredia R, Davila JC, Guirado S. Efferent retinal projections visualized by immunohistochemical detection of the estrogen-related receptor β in the postnatal and adult mouse brain. Neurosci Lett 2008; 438: 48-53
24 Grgurevic N, Tobet S, Majdic G. Widespread expression of liver receptor homolog 1 in mouse brain. Neuro Endocrinol Lett 2005; 26: 541-547
25 Seckl JR, Walker BR. Minireview: 11β-hydroxysteroid dehydrogenase type 1 – a tissue-specific amplifier of glucocorticoid action. Endocrinology 2001; 142: 1371-1376
26 Almad A, McTigue DM. Chronic expression of PPAR-δ by oligodendrocyte lineage cells in the injured rat spinal cord. J Comp Neurol 2010; 518: 785-799
27 D’Angelo B, Benedetti E, Di Loreto S, Cristiano L, Laurenti G, Ceru MP, Cimini A. Signal transduction pathways involved in PPARβ/δ-induced neuronal differentiation. J Cell Physiol 2011; 226: 2170-2180
28 Schnegg CI, Kooshki M, Hsu FC, Sui G, Robbins ME. PPARδ prevents radiation-induced proinflammatory responses in microglia via transrepression of NF-κB and inhibition of the PKCα/MEK1/2/ERK1/2/AP-1 pathway. Free Radic Biol Med 2012; 52: 1734-1743
29 Siegel DA, Davies P, Dobrenis K, Huang M. Tomoregulin-2 is found extensively in plaques in Alzheimer’s disease brain. J Neurochem 2006; 98: 34-44
30 Zhou XE, Suino-Powell KM, Xu Y, Chan CW, Tanabe O, Kruse SW, Reynolds R, Engel JD, Xu HE. The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor. J Biol Chem 2011; 286: 2877-2885
31 Sousa N, Almeida OF. Corticosteroids: Sculptors of the hippocampal formation. Rev Neurosci 2002; 13: 59-84
32 Kino T, Chrousos GP. Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes. J Endocrinol 2001; 169: 437-445
33 Chrousos GP. Glucocorticoid therapy. In: Felig P, Frohman LA. eds. Endocrinology & Metablism. 4^th ed. New York: McGraw-Hill; 2001: 609-632
34 Aimone JB, Wiles J, Gage FH. Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 2006; 9: 723-727
35 Kukolja J, Thiel CM, Wolf OT, Fink GR. Increased cortisol levels in cognitively challenging situations are beneficial in young but not older subjects. Psychopharmacology (Berl) 2008; 201: 293-304
36 Gass P, Kretz O, Wolfer DP, Berger S, Tronche F, Reichardt HM, Kellendonk C, Lipp HP, Schmid W, Schutz G. Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice. EMBO Rep 2000; 1: 447-451
37 Yu S, Yang S, Holsboer F, Sousa N, Almeida OF. Glucocorticoid regulation of astrocytic fate and function. PLoS One 2011; 6: e22419
38 Yu S, Patchev AV, Wu Y, Lu J, Holsboer F, Zhang JZ, Sousa N, Almeida OF. Depletion of the neural precursor cell pool by glucocorticoids. Ann Neurol 2010; 67: 21-30
39 Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 2008; 7: 854-868
40 Sun G, Yu RT, Evans RM, Shi Y. Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc Natl Acad Sci USA 2007; 104: 15282-15287
41 Sun G, Fu C, Shen C, Shi Y. Histone deacetylases in neural stem cells and induced pluripotent stem cells. J Biomed Biotechnol 2011; 2011: 835968
42 Chateauvieux S, Morceau F, Dicato M, Diederich M. Molecular and therapeutic potential and toxicity of valproic acid. J Biomed Biotechnol 2010; 2010: 479364
43 Faraco G, Cavone L, Chiarugi A. The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis. Mol Med 2011; 17: 442-447
44 Fischer A, Sananbenesi F, Mungenast A, Tsai LH. Targeting the correct HDAC(s) to treat cognitive disorders. Trends Pharmacol Sci 2010; 31: 605-617
45 Shein NA, Shohami E. Histone deacetylase inhibitors as therapeutic agents for acute central nervous system injuries. Mol Med 2011; 17: 448-456

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