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Breed-specific expression of GR exon 1 mRNA variants and profile of GR promoter CpG methylation in the hippocampus of newborn piglets

Published online by Cambridge University Press:  08 July 2014

Q. Sun ,
Y. Jia ,
R. Li ,
X. Li ,
X. Yang  and
R. Zhao
Q. Sun
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
Y. Jia
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
R. Li
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
X. Li
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
X. Yang
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
R. Zhao*
Affiliation:
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P. R. China
*
†E-mail: zhao.ruqian@gmail.com
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Abstract

Glucocorticoid receptor (GR) transcription is driven by alternative promoters to produce different exon 1 mRNA variants. CpG methylation on GR promoters profoundly affects GR transcription. GR in hippocampus is critical for energy homeostasis and stress responses, yet it remains unclear whether hippocampal expression of GR exon 1 mRNA variants and the methylation status of GR promoters differ between Large White (LW) and Erhualian (EHL) pigs showing distinct metabolic and stress-coping characteristics. EHL pigs had higher hippocampus weight relative to BW (P<0.01), which was associated with higher serum cortisol level compared with LW pigs. Hippocampal expression of brain-derived neurotrophic factor (P<0.05) was significantly higher, while Bax, a pro-apoptotic gene, was significantly lower in EHL pigs (P<0.05). Hippocampal expression of total GR did not differ between breeds, yet GR exon 1 to 11 mRNA was significantly higher (P<0.01) in EHL pigs, which was associated with a trend of increase (P=0.057) in GR protein content. No significant breed difference was detected for the methylation status across the whole region of the proximal GR promoter, while CpG334 and CpG266.267 were differentially methylated, in a reversed manner, between breeds. The methylation status of CpGs 248, 259, 260, 268 and 271 was negatively correlated (P<0.05) with GR exon 1 to 11 mRNA abundance. Our results provide fundamental information on the breed-specific characteristics of GR and its mRNA variants expression and the status of DNA methylation on the proximal GR promoter in the pig hippocampus.

Keywords

glucocorticoid receptorhippocampusmethylationpigvariant
Type
Research Article
Information
animal , Volume 8 , Issue 11 , November 2014 , pp. 1851 - 1856
Copyright
© The Animal Consortium 2014 

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References

Bartrup, JT, Moorman, JM and Newberry, NR 1997. BDNF enhances neuronal growth and synaptic activity in hippocampal cell cultures. Neuroreport 8, 3791–3794.Google Scholar
Cao-Lei, L, Suwansirikul, S, Jutavijittum, P, Meriaux, SB, Turner, JD and Muller, CP 2013. Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain. Journal of Psychiatric Research 47, 1597–1607.Google Scholar
Carrion, VG, Weems, CF and Reiss, AL 2007. Stress predicts brain changes in children: a pilot longitudinal study on youth stress, posttraumatic stress disorder, and the hippocampus. Pediatrics 119, 509–516.CrossRefGoogle ScholarPubMed
Cassady, JP 2007. Evidence of phenotypic relationships among behavioral characteristics of individual pigs and performance. Journal of Animal Science 85, 218–224.Google Scholar
Cintra, L, Granados, L, Aguilar, A, Kemper, T, DeBassio, W, Galler, J, Morgane, P, Duran, P and Diaz-Cintra, S 1997. Effects of prenatal protein malnutrition on mossy fibers of the hippocampal formation in rats of four age groups. Hippocampus 7, 184–191.Google Scholar
Desautes, C, Sarrieau, A, Caritez, JC and Mormede, P 1999. Behavior and pituitary-adrenal function in Large White and Meishan pigs. Domestic Animal Endocrinology 16, 193–205.CrossRefGoogle ScholarPubMed
Gadek-Michalska, A, Spyrka, J, Rachwalska, P, Tadeusz, J and Bugajski, J 2013. Influence of chronic stress on brain corticosteroid receptors and HPA axis activity. Pharmacological Reports 65, 1163–1175.CrossRefGoogle ScholarPubMed
Hwang, L, Choi, IY, Kim, SE, Ko, IG, Shin, MS, Kim, CJ, Kim, SH, Jin, JJ, Chung, JY and Yi, JW 2013. Dexmedetomidine ameliorates intracerebral hemorrhage-induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus. International Journal of Molecular Medicine 31, 1047–1056.Google Scholar
Jiang, Z, Qian, L, Zou, H, Jia, Y, Ni, Y, Yang, X and Zhao, R 2014. Porcine glucocorticoid receptor (NR3C1) gene: tissue-specificity of transcriptional strength and glucocorticoid responsiveness of alternative promoters. The Journal of Steroid Biochemistry and Molecular Biology 141C, 87–93.Google Scholar
Joels, M, Verkuyl, JM and Van Riel, E 2003. Hippocampal and hypothalamic function after chronic stress. Annals of the New York Academy of Sciences 1007, 367–378.Google Scholar
Li, X, Yang, X, Shan, B, Shi, J, Xia, D, Wegner, J and Zhao, R 2009. Meat quality is associated with muscle metabolic status but not contractile myofiber type composition in premature pigs. Meat Science 81, 218–223.CrossRefGoogle Scholar
Lillycrop, KA, Slater-Jefferies, JL, Hanson, MA, Godfrey, KM, Jackson, AA and Burdge, GC 2007. Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. The British Journal of Nutrition 97, 1064–1073.Google Scholar
Livak, KJ and Schmittgen, TD 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402–408.Google Scholar
Lu, NZ and Cidlowski, JA 2006. Glucocorticoid receptor isoforms generate transcription specificity. Trends in Cell Biology 16, 301–307.CrossRefGoogle ScholarPubMed
McGowan, PO, Sasaki, A, D’Alessio, AC, Dymov, S, Labonte, B, Szyf, M, Turecki, G and Meaney, MJ 2009. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience 12, 342–348.Google Scholar
Morgane, PJ, Mokler, DJ and Galler, JR 2002. Effects of prenatal protein malnutrition on the hippocampal formation. Neuroscience and Biobehavioral Reviews 26, 471–483.CrossRefGoogle ScholarPubMed
Neeley, EW, Berger, R, Koenig, JI and Leonard, S 2011. Prenatal stress differentially alters brain-derived neurotrophic factor expression and signaling across rat strains. Neuroscience 187, 24–35.CrossRefGoogle ScholarPubMed
Noorlander, CW, Tijsseling, D, Hessel, EV, de Vries, WB, Derks, JB, Visser, GH and de Graan, PN 2014. Antenatal glucocorticoid treatment affects hippocampal development in mice. PLoS One 9, e85671.Google Scholar
Oberlander, TF, Weinberg, J, Papsdorf, M, Grunau, R, Misri, S and Devlin, AM 2008. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3, 97–106.Google Scholar
Peters, A 2011. The selfish brain: competition for energy resources. American Journal of Human Biology 23, 29–34.Google Scholar
Pujols, L, Mullol, J, Roca-Ferrer, J, Torrego, A, Xaubet, A, Cidlowski, JA and Picado, C 2002. Expression of glucocorticoid receptor alpha- and beta-isoforms in human cells and tissues. American Journal of Physiology. Cell Physiology 283, C1324–C1331.CrossRefGoogle ScholarPubMed
Reyer, H, Ponsuksili, S, Wimmers, K and Murani, E 2013. Transcript variants of the porcine glucocorticoid receptor gene (NR3C1). General and Comparative Endocrinology 189, 127–133.Google Scholar
Rose, AJ and Herzig, S 2013. Metabolic control through glucocorticoid hormones: an update. Molecular and Cellular Endocrinology 380, 65–78.Google Scholar
Russcher, H, Vash, D, de Jong, FH, Brinkmann, AO, Hofland, LJ, Lamberts, SWJ and Koper, JW 2007. Associations between promoter usage and alternative splicing of the glucocorticoid receptor gene. Journal of Molecular Endocrinology 38, 91–98.Google Scholar
Schaaf, MJ, de Jong, J, de Kloet, ER and Vreugdenhil, E 1998. Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone. Brain Research 813, 112–120.Google Scholar
Schaefers, AT 2013. Rearing conditions and domestication background determine regulation of hippocampal cell proliferation and survival in adulthood-laboratory CD1 and C57Bl/6 mice versus wild house mice. Neuroscience 228, 120–127.Google Scholar
Turner, JD, Schote, AB, Macedo, JA, Pelascini, LP and Muller, CP 2006. Tissue specific glucocorticoid receptor expression, a role for alternative first exon usage? Biochemical Pharmacology 72, 1529–1537.Google Scholar
Turner, JD, Alt, SR, Cao, L, Vernocchi, S, Trifonova, S, Battello, N and Muller, CP 2010. Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more. Biochemical Pharmacology 80, 1860–1868.Google Scholar
van Steensel, B, van Binnendijk, EP, Hornsby, CD, van der Voort, HT, Krozowski, ZS, de Kloet, ER and van Driel, R 1996. Partial colocalization of glucocorticoid and mineralocorticoid receptors in discrete compartments in nuclei of rat hippocampus neurons. Journal of Cell Science 109 (Pt 4), 787–792.Google Scholar
Weaver, IC, Cervoni, N, Champagne, FA, D’Alessio, AC, Sharma, S, Seckl, JR, Dymov, S, Szyf, M and Meaney, MJ 2004. Epigenetic programming by maternal behavior. Nature Neuroscience 7, 847–854.Google Scholar
Wei, S, Xia, D, Li, LU, Xiao, JS, Bao, JW, Parvizi, N and Zhao, RQ 2010. Breed-specific expression of hippocampal 11 beta-hydroxysteroid dehydrogenases and glucocorticoid receptors in Erhualian and Pietrain pigs exhibiting distinct stress coping characteristics. Livestock Science 131, 240–244.Google Scholar
Yang, XJ, Liu, R, Albrecht, E, Dong, X, Maak, S and Zhao, RQ 2012. Breed-specific patterns of hepatic gluconeogenesis and glucocorticoid action in pigs. Archiv Tierzucht 55, 152–162.Google Scholar
Yau, JL, Noble, J, Chapman, KE and Seckl, JR 2004. Differential regulation of variant glucocorticoid receptor mRNAs in the rat hippocampus by the antidepressant fluoxetine. Brain Research 129, 189–192.Google Scholar
Yu, IT, Lee, SH, Lee, YS and Son, H 2004. Differential effects of corticosterone and dexamethasone on hippocampal neurogenesis in vitro. Biochemical and Biophysical Research Communications 317, 484–490.Google Scholar
Zou, H, Li, R, Jia, Y, Yang, X, Ni, Y, Cong, R, Soloway, PD and Zhao, R 2012. Breed-dependent transcriptional regulation of 5'-untranslated GR (NR3C1) exon 1 mRNA variants in the liver of newborn piglets. PLoS One 7, e40432.Google Scholar
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