Preterm birth: A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury

Science Translational Medicine

Volumn 3, Issue 105, 2011, Pages

  Heine, Vivi M ^a,b,d   Griveau, Amelie ^a,b   Chapin, Cheryl ^a   Ballard, Philip L ^a   Chen, James K ^c   Rowitch, David H ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

NEUROPROTECTIVE AGENT; SONIC HEDGEHOG SMOOTHENED SMALL MOLECULE AGONIST; UNCLASSIFIED DRUG; CYCLOHEXYLAMINE DERIVATIVE; G PROTEIN COUPLED RECEPTOR; GLUCOCORTICOID; PREDNISOLONE; SAG COMPOUND; SHH PROTEIN, MOUSE; SMO PROTEIN, MOUSE; SONIC HEDGEHOG PROTEIN; THIOPHENE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; CEREBELLUM INJURY; CONTROLLED STUDY; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG EFFECT; DRUG SAFETY; FEMALE; FETUS; FETUS LUNG MATURATION; HUMAN; HUMAN TISSUE; IN VIVO STUDY; LOW DRUG DOSE; LUNG DEVELOPMENT; MALE; MOUSE; NEUROPROTECTION; NEUROTOXICITY; NEWBORN; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR VASCULARIZATION; ANIMAL; BRAIN INJURY; C57BL MOUSE; CELL CULTURE; CEREBELLUM; CHEMICALLY INDUCED DISORDER; DRUG POTENTIATION; INJURY;

ANIMALS; BRAIN INJURIES; CELLS, CULTURED; CEREBELLUM; CYCLOHEXYLAMINES; GLUCOCORTICOIDS; HEDGEHOG PROTEINS; MICE; MICE, INBRED C57BL; PREDNISOLONE; RECEPTORS, G-PROTEIN-COUPLED; THIOPHENES;

EID: 80054783712     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002731     Document Type: Article

References (44)

1. M. C. Allen, Neurodevelopmental outcomes of preterm infants. Curr. Opin. Neurol. 21, 123-128 (2008).
2. L. W. Doyle, P. J. Anderson, Adult outcome of extremely preterm infants. Pediatrics 126, 342-351 (2010).
3. M. Yanney, N. Marlow, Paediatric consequences of fetal growth restriction. Semin. Fetal Neonatal Med. 9, 411-418 (2004).
4. M. P. Allin, S. Salaria, C. Nosarti, J. Wyatt, L. Rifkin, R. M. Murray, Vermis and lateral lobes of the cerebellum in adolescents born very preterm. Neuroreport 16, 1821-1824 (2005).
5. J. B. Bodensteiner, S. D. Johnsen, Cerebellar injury in the extremely premature infant: Newly recognized but relatively common outcome. J. Child Neurol. 20, 139-142 (2005).
6. C. Limperopoulos, J. S. Soul, K. Gauvreau, P. S. Huppi, S. K. Warfield, H. Bassan, R. L. Robertson, J. J. Volpe, A. J. du Plessis, Late gestation cerebellar growth is rapid and impeded by premature birth. Pediatrics 115, 688-695 (2005).
7. J. J. Volpe, Cerebellum of the premature infant: Rapidly developing, vulnerable, clinically important. J. Child Neurol. 24, 1085-1104 (2009).
8. A. Tavano, R. Grasso, C. Gagliardi, F. Triulzi, N. Bresolin, F. Fabbro, R. Borgatti, Disorders of cognitive and affective development in cerebellar malformations. Brain 130, 2646-2660 (2007).
9. A. M. Kenney, H. R. Widlund, D. H. Rowitch, Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Development 131, 217-228 (2004).
10. J. D. Corrales, S. Blaess, E. M. Mahoney, A. L. Joyner, The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation. Development 133, 1811-1821 (2006).
11. R. J. Wechsler-Reya, M. P. Scott, Control of neuronal precursor proliferation in the cerebellum by Sonic hedgehog. Neuron 22, 103-114 (1999).
12. P. Rakic, R. L. Sidman, Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J. Comp. Neurol. 139, 473-500 (1970).
13. R. D. Adams, M. Victor, A. H. Ropper, Principles of Neurology (McGraw-Hill, New York, 1997), p. 1618.
14. P. M. Lewis, A. Gritli-Linde, R. Smeyne, A. Kottmann, A. P. McMahon, Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev. Biol. 270, 393-410 (2004).
15. 1 cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol. Cell. Biol. 20, 9055-9067 (2000).
16. A. M. Kenney, M. D. Cole, D. H. Rowitch, Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130, 15-28 (2003).
17. A. M. Dubuc, P. A. Northcott, S. Mack, H. Witt, S. Pfister, M. D. Taylor, The genetics of pediatric brain tumors. Curr. Neurol. Neurosci. Rep. 10, 215-223 (2010).
18. U. Schüller, V. M. Heine, J. Mao, A. T. Kho, A. K. Dillon, Y. G. Han, E. Huillard, T. Sun, A. H. Ligon, Y. Qian, Q. Ma, A. Alvarez-Buylla, A. P. McMahon, D. H. Rowitch, K. L. Ligon, Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14, 123-134 (2008).
19. M. F. Beers, H. Shuman, H. G. Liley, J. Floros, L. W. Gonzales, N. Yue, P. L. Ballard, Surfactant protein B in human fetal lung: Developmental and glucocorticoid regulation. Pediatr. Res. 38, 668-675 (1995).
20. V. M. Heine, D. H. Rowitch, Hedgehog signaling has a protective effect in glucocorticoid-induced mouse neonatal brain injury through an 11bHSD2-dependent mechanism. J. Clin. Invest. 119, 267-277 (2009).
21. C. R. Edwards, R. Benediktsson, R. S. Lindsay, J. R. Seckl, 11b-Hydroxysteroid dehydrogenases: Key enzymes in determining tissue-specific glucocorticoid effects. Steroids 61, 263-269 (1996).
22. M. C. Holmes, M. Sangra, K. L. French, I. R. Whittle, J. Paterson, J. J. Mullins, J. R. Seckl, 11β- Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids. Neuroscience 137, 865-873 (2006).
23. F. J. Frey, G. Escher, B. M. Frey, Pharmacology of 11β- hydroxysteroid dehydrogenase. Steroids 59, 74-79 (1994).
24. R. Diaz, R. W. Brown, J. R. Seckl, Distinct ontogeny of glucocorticoid and mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase types I and II mRNAs in the fetal rat brain suggest a complex control of glucocorticoid actions. J. Neurosci. 18, 2570-2580 (1998).
25. M. Beato, A. Sánchez-Pacheco, Interaction of steroid hormone receptors with the transcription initiation complex. Endocr. Rev. 17, 587-609 (1996).
26. N. A. Datson, M. C. Morsink, O. C. Meijer, E. R. de Kloet, Central corticosteroid actions: Search for gene targets. Eur. J. Pharmacol. 583, 272-289 (2008).
27. J. K. Chen, J. Taipale, K. E. Young, T. Maiti, P. A. Beachy, Small molecule modulation of Smoothened activity. Proc. Natl. Acad. Sci. U.S.A. 99, 14071-14076 (2002).
28. M. Frank-Kamenetsky, X. M. Zhang, S. Bottega, O. Guicherit, H. Wichterle, H. Dudek, D. Bumcrot, F. Y. Wang, S. Jones, J. Shulok, L. L. Rubin, J. A. Porter, Small-molecule modulators of Hedgehog signaling: Identification and characterization of Smoothened agonists and antagonists. J. Biol. 1, 10 (2002).
29. O. J. Becher, D. Hambardzumyan, E. I. Fomchenko, H. Momota, L. Mainwaring, A. M. Bleau, A. M. Katz, M. Edgar, A. M. Kenney, C. Cordon-Cardo, R. G. Blasberg, E. C. Holland, Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas. Cancer Res. 68, 2241-2249 (2008).
30. L. Lum, P. A. Beachy, The Hedgehog response network: Sensors, switches, and routers. Science 304, 1755-1759 (2004).
31. H. Masuya, M. Inoue, Y. Wada, A. Shimizu, J. Nagano, A. Kawai, A. Inoue, T. Kagami, T. Hirayama, A. Yamaga, H. Kaneda, K. Kobayashi, O. Minowa, I. Miura, Y. Gondo, T. Noda, S. Wakana, T. Shiroishi, Implementation of the modified-SHIRPA protocol for screening of dominant phenotypes in a large-scale ENU mutagenesis program. Mamm. Genome 16, 829-837 (2005).
32. J. D. Kessler, H. Hasegawa, S. N. Brun, B. A. Emmenegger, Z. J. Yang, J. W. Dutton, F. Wang, R. J. Wechsler-Reya, N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma. Genes Dev. 23, 157-170 (2009).
33. K. K. Noguchi, K. C. Walls, D. F. Wozniak, J. W. Olney, K. A. Roth, N. B. Farber, Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death. Cell Death Differ. 15, 1582-1592 (2008).
34. S. R. Hintz, D. E. Kendrick, D. E. Wilson-Costello, A. Das, E. F. Bell, B. R. Vohr, R. D. Higgins; NICHD Neonatal Research Network, Early-childhood neurodevelopmental outcomes are not improving for infants born at <25 weeks' gestational age. Pediatrics 127, 62-70 (2011).
35. S. R. Dalziel, V. K. Lim, A. Lambert, D. McCarthy, V. Parag, A. Rodgers, J. E. Harding, Antenatal exposure to betamethasone: Psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ 331, 665 (2005).
36. G. C. Liggins, R. N. Howie, A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 50, 515-525 (1972).
37. D. Wilson-Costello, M. C. Walsh, J. C. Langer, R. Guillet, A. R. Laptook, B. J. Stoll, S. Shankaran, N. N. Finer, K. P. Van Meurs, W. A. Engle, A. Das; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Impact of postnatal corticosteroid use on neurodevelopment at 18 to 22 months' adjusted age: Effects of dose, timing, and risk of bronchopulmonary dysplasia in extremely low birth weight infants. Pediatrics 123, e430-e437 (2009).
38. T. F. Yeh, Y. J. Lin, H. C. Lin, C. C. Huang, W. S. Hsieh, C. H. Lin, C. H. Tsai, Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N. Engl. J. Med. 350, 1304-1313 (2004).
39. E. W. Y. Tam, V. Chau, D. M. Ferriero, A. J. Barkovich, K. J. Poskitt, C. Studholme, E. D.-Y. Fok, R. E. Grunau, D. V. Glidden, S. P. Miller, Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids. Sci. Transl. Med. 3, 105ra105 (2011).
40. L. V. Goodrich, L. Milenković, K. M. Higgins, M. P. Scott, Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109-1113 (1997).
41. J. T. Romer, T. Curran, Medulloblastoma and retinoblastoma: Oncology recapitulates ontogeny. Cell Cycle 3, 917-919 (2004).
42. L. W. Gonzales, P. L. Ballard, R. Ertsey, M. C. Williams, Glucocorticoids and thyroid hormones stimulate biochemical and morphological differentiation of human fetal lung in organ culture. J. Clin. Endocrinol. Metab. 62, 678-691 (1986).
43. V. C. Venkatesh, D. M. Iannuzzi, R. Ertsey, P. L. Ballard, Differential glucocorticoid regulation of the pulmonary hydrophobic surfactant proteins SP-B and SP-C. Am. J. Respir. Cell Mol. Biol. 8, 222-228 (1993).
44. Acknowledgments: We thank A. M. Barette, S. Kaing, and M. Wong for expert technical assistance; J. Otero, E. Huang, B. Hann, and the UCSF Comprehensive Cancer Center pathology core for blood and whole-body solid tumor screening; L. Gonzales for fetal lung cultures; and E. Holland for providing Gli-luciferase mice. Funding: V.M.H. thanks the Netherlands Organization for Scientific Research for a TALENT stipend. A.G. is grateful for support by a fellowship from the American Brain Tumor Association. This work was supported by grants from the March of Dimes Foundation (to D.H.R.) and NIH (R01 CA136574 to J.K.C.; R01 NS047527 to D.H.R.; RO1 HL086323 and PO1 HL024075 to P.L.B.). D.H.R. is a Howard Hughes Medical Institute Investigator. Author contributions: V.M.H., C.C., and A.G. acquired and analyzed the data. V.M.H., J.K.C., and D.H.R. conceived the study. All authors designed the experiments and wrote the manuscript. Competing interests: The authors declare that they have no competing interests. The SAG compound was synthesized at Stanford University and is available under a materials transfer agreement.