Skip to main content Accessibility help
×
Home
Hostname: page-component-564cf476b6-z65vl Total loading time: 0.299 Render date: 2021-06-21T10:24:51.765Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true }

Altered expression and chromatin structure of the hippocampal IGF1r gene is associated with impaired hippocampal function in the adult IUGR male rat

Published online by Cambridge University Press:  09 January 2012

D. Caprau
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
M. E. Schober
Affiliation:
Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA
K. Bass
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
S. O'Grady
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
X. Ke
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
B. Block
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
C. W. Callaway
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
M. Hale
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
X. Yu
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
R. A. McKnight
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
R. P. Kesner
Affiliation:
Department of Psychology, University of Utah School of Medicine, Salt Lake City, Utah, USA
R. H. Lane
Affiliation:
Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
Corresponding
E-mail address:

Abstract

Exposure to intrauterine growth restriction (IUGR) is an important risk factor for impaired learning and memory, particularly in males. Although the basis of IUGR-associated learning and memory dysfunction is unknown, potential molecular participants may be insulin-like growth factor 1 (Igf1) and its receptor, IGF1r. We hypothesized that transcript levels and protein abundance of Igf1 and IGF1r in the hippocampus, a brain region critical for learning and memory, would be lower in IUGR male rats than in age-matched male controls at birth (postnatal day 0, P0), at weaning (P21) and adulthood (P120). We also hypothesized that changes in messenger Ribonucleic acid (mRNA) transcript levels and protein abundance would be associated with specific histone marks in IUGR male rats. Lastly, we hypothesized that IUGR male rats would perform poorer on tests of hippocampal function at P120. IUGR was induced by bilateral ligation of the uterine arteries in pregnant dams at embryonic day 19 (term is 21 days). Hippocampal Igf1 mRNA transcript levels and protein abundance were unchanged in IUGR male rats at P0, P21 or P120. At P0 and P120, IGF1r expression was increased in IUGR male rats. At P21, IGF1r expression was decreased in IUGR male rats. Increased IGF1r expression was associated with more histone 3 lysine 4 dimethylation (H3K4Me2) in the promoter region. In addition, IUGR male rats performed poorer on intermediate-term spatial working memory testing at P120. We speculate that altered IGF1r expression in the hippocampus of IUGR male rats may play a role in learning and memory dysfunction later in life.

Type
Original Articles
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

Access options

Get access to the full version of this content by using one of the access options below.

Footnotes

D. Caprau and M. Schober contributed equally to this work.

References

1. Gagnon, R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol. 2003; 110 (Suppl 1), S99S107.Google Scholar
2. Fouron, JC, Gosselin, J, Raboisson, MJ, et al. The relationship between an aortic isthmus blood flow velocity index and the postnatal neurodevelopmental status of fetuses with placental circulatory insufficiency. Am J Obstet Gynecol. 2005; 192, 497503.Google Scholar
3. Ley, D, Marsal, K, Dahlgren, J, Hellstrom, A. Abnormal retinal optic nerve morphology in young adults after intrauterine growth restriction. Pediatr Res. 2004; 56, 139143.Google Scholar
4. Leitner, Y, Fattal-Valevski, A, Geva, R, et al. Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study. J Child Neurol. 2007; 22, 580587.Google Scholar
5. Frisk, V, Amsel, R, Whyte, HE. The importance of head growth patterns in predicting the cognitive abilities and literacy skills of small-for-gestational-age children. Dev Neuropsychol. 2002; 22, 565593.Google Scholar
6. Leitner, Y, Fattal-Valevski, A, Geva, R, et al. Six-year follow-up of children with intrauterine growth retardation: long-term, prospective study. J Child Neurol. 2000; 15, 781786.Google Scholar
7. Sung, IK, Vohr, B, Oh, W. Growth and neurodevelopmental outcome of very low birth weight infants with intrauterine growth retardation: comparison with control subjects matched by birth weight and gestational age. J Pediatr. 1993; 123, 618624.Google Scholar
8. Zubrick, SR, Kurinczuk, JJ, McDermott, BM, et al. Fetal growth and subsequent mental health problems in children aged 4 to 13 years. Dev Med Child Neurol. 2000; 42, 1420.Google Scholar
9. Paz, I, Gale, R, Laor, A, et al. The cognitive outcome of full-term small for gestational age infants at late adolescence. Obstet Gynecol. 1995; 85, 452456.Google Scholar
10. Strauss, RS. Adult functional outcome of those born small for gestational age: twenty-six-year follow-up of the 1970 British Birth Cohort. JAMA. 2000; 283, 625632.Google Scholar
11. Rooney, R, Hay, D, Levy, F. Small for gestational age as a predictor of behavioral and learning problems in twins. Twin Res. 2003; 6, 4654.Google Scholar
12. Jarvis, S, Glinianaia, SV, Arnaud, C, et al. Case gender and severity in cerebral palsy varies with intrauterine growth. Arch Dis Child. 2005; 90, 474479.Google Scholar
13. Torres-Aleman, I. Toward a comprehensive neurobiology of IGF-I. Dev Neurobiol. 2010; 70, 384396.Google Scholar
14. Joseph D'Ercole, A, Ye, P. Expanding the mind: insulin-like growth factor I and brain development. Endocrinology. 2008; 149, 59585962.Google Scholar
15. Aberg, ND, Brywe, KG, Isgaard, J. Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain. ScientificWorldJournal. 2006; 6, 5380.Google Scholar
16. Liu, W, Ye, P, O'Kusky, JR, D'Ercole, AJ. Type 1 insulin-like growth factor receptor signaling is essential for the development of the hippocampal formation and dentate gyrus. J Neurosci Res. 2009; 87, 28212832.Google Scholar
17. Chen, MJ, Russo-Neustadt, AA. Running exercise- and antidepressant-induced increases in growth and survival-associated signaling molecules are IGF-dependent. Growth Factors. 2007; 25, 118131.Google Scholar
18. Trejo, JL, Carro, E, Torres-Aleman, I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci. 2001; 21, 16281634.Google Scholar
19. Trejo, JL, Llorens-Martin, MV, Torres-Aleman, I. The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci. 2008; 37, 402411.Google Scholar
20. Trejo, JL, Piriz, J, Llorens-Martin, MV, et al. Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Mol Psychiatry. 2007; 12, 11181128.Google Scholar
21. Tosh, DN, Fu, Q, Callaway, CW, et al. Epigenetics of programmed obesity: alteration in IUGR rat hepatic IGF1 mRNA expression and histone structure in rapid vs. delayed postnatal catch-up growth. Am J Physiol Gastrointest Liver Physiol. 2010; 299, G1023G1029.Google Scholar
22. Chatelain, PG, Nicolino, M, Claris, O, Salle, B, Chaussain, J. Multiple hormone resistance in short children born with intrauterine growth retardation? Horm Res. 1998; 49, 2022.Google Scholar
23. Lee, MH, Jeon, YJ, Lee, SM, et al. Placental gene expression is related to glucose metabolism and fetal cord blood levels of insulin and insulin-like growth factors in intrauterine growth restriction. Early Hum Dev. 2010; 86, 4550.Google Scholar
24. Bai, B, Yao, Y, Li, W, Zeng, Y, Yang, F. The relationships of the serum concentrations of insulin-like growth factors in fetal rats with intrauterine growth retardation. Hua Xi Yi Ke Da Xue Xue Bao. 2001; 32, 307308, 312.Google Scholar
25. Fu, Q, Yu, X, Callaway, CW, Lane, RH, McKnight, RA. Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene. FASEB J. 2009; 23, 24382449.Google Scholar
26. Lu, NZ, Cidlowski, JA. Glucocorticoid receptor isoforms generate transcription specificity. Trends Cell Biol. 2006; 16, 301307.Google Scholar
27. Barros, SP, Offenbacher, S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res. 2009; 88, 400408.Google Scholar
28. El-Osta, A, Brasacchio, D, Yao, D, et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008; 205, 24092417.Google Scholar
29. Cheutin, T, McNairn, AJ, Jenuwein, T, et al. Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science. 2003; 299, 721725.Google Scholar
30. Ng, HH, Bird, A. DNA methylation and chromatin modification. Curr Opin Genet Dev. 1999; 9, 158163.Google Scholar
31. Fu, Q, McKnight, RA, Yu, X, Callaway, CW, Lane, RH. Growth retardation alters the epigenetic characteristics of hepatic dual specificity phosphatase 5. FASEB J. 2006; 20, 21272129.Google Scholar
32. Ke, X, Schober, ME, McKnight, RA, et al. Intrauterine growth retardation affects expression and epigenetic characteristics of the rat hippocampal glucocorticoid receptor gene. Physiol Genomics. 2010; 42, 177189.Google Scholar
33. O'Grady, SP, Caprau, D, Ke, XR, et al. Intrauterine growth restriction alters hippocampal expression and chromatin structure of Cyp19a1 variants. Syst Biol Reprod Med. 2010; 56, 292302.Google Scholar
34. Schober, ME, McKnight, RA, Yu, X, et al. Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi. Am J Physiol Regul Integr Comp Physiol. 2009; 296, R681R692.Google Scholar
35. Ke, X, McKnight, RA, Wang, ZM, et al. Nonresponsiveness of cerebral p53-MDM2 functional circuit in newborn rat pups rendered IUGR via uteroplacental insufficiency. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R1038R1045.Google Scholar
36. Mallard, C, Loeliger, M, Copolov, D, Rees, S. Reduced number of neurons in the hippocampus and the cerebellum in the postnatal guinea-pig following intrauterine growth-restriction. Neuroscience. 2000; 100, 327333.Google Scholar
37. Rees, S, Bocking, AD, Harding, R. Structure of the fetal sheep brain in experimental growth retardation. J Dev Physiol. 1988; 10, 211225.Google Scholar
38. Ke, X, Lei, Q, James, SJ, et al. Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genomics. 2006; 25, 1628.Google Scholar
39. Guiding principles for research involving animals and human beings. Am J Physiol Regul Integr Comp Physiol. 2002; 283, R281R283.Google Scholar
40. Lane, RH, Crawford, SE, Flozak, AS, Simmons, RA. Localization and quantification of glucose transporters in liver of growth-retarded fetal and neonatal rats. Am J Physiol. 1999; 276 (1 Pt 1), E135E142.Google Scholar
41. Menon, RK, Shaufl, A, Yu, JH, Stephan, DA, Friday, RP. Identification and characterization of a novel transcript of the murine growth hormone receptor gene exhibiting development- and tissue-specific expression. Mol Cell Endocrinol. 2001; 172, 135146.Google Scholar
42. Fu, Q, McKnight, RA, Yu, X, et al. Uteroplacental insufficiency induces site-specific changes in histone H3 covalent modifications and affects DNA-histone H3 positioning in day 0 IUGR rat liver. Physiol Genomics. 2004; 20, 108116.Google Scholar
43. Werner, H, Bach, MA, Stannard, B, Roberts, CT Jr, LeRoith, D. Structural and functional analysis of the insulin-like growth factor I receptor gene promoter. Mol Endocrinol. 1992; 6, 15451558.Google Scholar
44. Werner, H, Hernandez-Sanchez, C, Karnieli, E, Leroith, D. The regulation of IGF-I receptor gene expression. Int J Biochem Cell Biol. 1995; 27, 987994.Google Scholar
45. Lan, F, Collins, RE, De Cegli, R, et al. Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression. Nature. 2007; 448, 718722.Google Scholar
46. Lu, Y, Liu, XM, Li, SQ. Effects of L-arginine on the expression of insulin-like growth factors and insulin-like growth factor binding protein 3 in rats with intrauterine growth retardation. Zhongguo Dang Dai Er Ke Za Zhi. 2006; 8, 319322.Google Scholar
47. Yamasaki, H, Prager, D, Melmed, S. Structure-function of the human insulin-like growth factor-I receptor: a discordance of somatotroph internalization and signaling. Mol Endocrinol. 1993; 7, 681685.Google Scholar
48. Pehar, M, O'Riordan, KJ, Burns-Cusato, M, et al. Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death. Aging Cell. 2010; 9, 174190.Google Scholar
49. Maier, B, Gluba, W, Bernier, B, et al. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 2004; 18, 306319.Google Scholar
50. Vaissiere, T, Sawan, C, Herceg, Z. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res. 2008; 659, 4048.Google Scholar
51. Krebs, JE. Moving marks: dynamic histone modifications in yeast. Mol Biosyst. 2007; 3, 590597.Google Scholar
52. Dieker, J, Muller, S. Epigenetic histone code and autoimmunity. Clin Rev Allergy Immunol. 2010; 39, 7884.Google Scholar
53. Cheung, P, Allis, CD, Sassone-Corsi, P. Signaling to chromatin through histone modifications. Cell. 2000; 103, 263271.Google Scholar
54. Bloom, DC, Giordani, NV, Kwiatkowski, DL. Epigenetic regulation of latent HSV-1 gene expression. Biochim Biophys Acta. 2010; 1799, 246256.Google Scholar
55. Taverna, SD, Ilin, S, Rogers, RS, et al. Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs. Mol Cell. 2006; 24, 785796.Google Scholar
56. Stenvers, KL, Lund, PK, Gallagher, M. Increased expression of type 1 insulin-like growth factor receptor messenger RNA in rat hippocampal formation is associated with aging and behavioral impairment. Neuroscience. 1996; 72, 505518.Google Scholar
57. Lee, I, Hunsaker, MR, Kesner, RP. The role of hippocampal subregions in detecting spatial novelty. Behav Neurosci. 2005; 119, 145153.Google Scholar
58. Lee, I, Kesner, RP. Differential roles of dorsal hippocampal subregions in spatial working memory with short versus intermediate delay. Behav Neurosci. 2003; 117, 10441053.Google Scholar
59. Lee, I, Kesner, RP. Differential contributions of dorsal hippocampal subregions to memory acquisition and retrieval in contextual fear-conditioning. Hippocampus. 2004; 14, 301310.Google Scholar
60. Lee, I, Kesner, RP. Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory. Nat Neurosci. 2002; 5, 162168.Google Scholar
61. Vago, DR, Bevan, A, Kesner, RP. The role of the direct perforant path input to the CA1 subregion of the dorsal hippocampus in memory retention and retrieval. Hippocampus. 2007; 17, 977987.Google Scholar
62. Lane, RH, Maclennan, NK, Daood, MJ, et al. IUGR alters postnatal rat skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1 gene expression in a fiber specific manner. Pediatr Res. 2003; 53, 9941000.Google Scholar
63. Simmons, RA, Templeton, LJ, Gertz, SJ. Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes. 2001; 50, 22792286.Google Scholar
Supplementary material: Image

Caprau Supplementary Table

Table S1: Primers and Probes

Download Caprau Supplementary Table(Image)
Image 176 KB
12
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Altered expression and chromatin structure of the hippocampal IGF1r gene is associated with impaired hippocampal function in the adult IUGR male rat
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Altered expression and chromatin structure of the hippocampal IGF1r gene is associated with impaired hippocampal function in the adult IUGR male rat
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Altered expression and chromatin structure of the hippocampal IGF1r gene is associated with impaired hippocampal function in the adult IUGR male rat
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *