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The Effect of Growth Hormone on mRNA Expression of the GABAB1 Receptor Subunit and GH/IGF Axis Genes in a Mouse Model of Prader-Willi Syndrome
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 Title & Authors
The Effect of Growth Hormone on mRNA Expression of the GABAB1 Receptor Subunit and GH/IGF Axis Genes in a Mouse Model of Prader-Willi Syndrome
Lee, Jin Young; Jin, Dong-Kyu;
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Purpose: Growth hormone (GH) therapy substantially improves several cognitive functions in PWS. However, the molecular mechanisms underlying the beneficial effects of GH on cognition remain unclear in PWS. In this study, we investigated the effects of recombinant human GH on the gene expression of GABAB receptor subunits and GH/insulin-like growth factor (IGF) axis genes in the brain regions of PWS-mimicking mice (Snord116del). Methods: Snord116del mice were injected subcutaneously with 1.0 mg/kg GH or saline, once daily for 7 days. The collected brain tissues were analyzed for mRNA content using quantitative PCR (qPCR) in the cerebellum, hippocampus, and cerebral cortex. Results: GH increased the mRNA expression level of the receptor subunit () and IGF-1R in the cerebellum. Furthermore, a significant positive correlation was found between the level of mRNA and the expression of the IGF-1R transcript. GH also induced an increase in the mRNA expression of IGF-2 and IGF-2R in the cerebellum. Conclusion: These data indicate that GH may provide beneficial effects on cognitive function through its influences on the expression of and GH/IGF-1 axis genes in PWS patients.
Prader-Willi syndrome;Snord116del mice;Cognitive impairment;Growth hormone; receptor subunit;
 Cited by
Cassidy SB. Prader-Willi syndrome. J Med Genet (5.703) 1997;34:917-23. crossref(new window)

Swaab DF, Purba JS, Hofman MA. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. J Clin Endocrinol Metab 1995;80:573-9.

Festen DA, Wevers M, Lindgren AC, Böhm B, Otten BJ, Wit JM, et al. Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2008;68:919-25. crossref(new window)

Myers SE, Whitman BY, Carrel AL, Moerchen V, Bekx MT, Allen DB. Two years of growth hormone therapy in young children with Prader-Willi syndrome: physical and neurodevelopmental benefits. Am J Med Genet A 2007;143A:443-8. crossref(new window)

Hoybye C, Thoren M, Bohm B. Cognitive, emotional, physical and social effects of growth hormone treatment in adults with Prader-Willi syndrome. J Intellect Disabil Res 2005;49:245-52. crossref(new window)

Siemensma EP, Tummers-de Lind van Wijngaarden RF, Festen DA, Troeman ZC, van Alfen-van der Velden AA, Otten BJ, et al. Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study. J Clin Endocrinol Metab 2012;97:2307-14. crossref(new window)

Sonntag WE, Ramsey M, Carter CS. Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging. Ageing Res Rev 2005;4:195-212. crossref(new window)

Nyberg F, Hallberg M. Growth hormone and cognitive function. Nat Rev Endocrinol 2013;9:357-65. crossref(new window)

Le Greves M, Zhou Q, Berg M, Le Grevès P, Fhölenhag K, Meyerson B, et al. Growth hormone replacement in hypophysectomized rats affects spatial performance and hippocampal levels of NMDA receptor subunit and PSD-95 gene transcript levels. Exp Brain Res 2006;173:267-73. crossref(new window)

Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, et al. A critical role for IGFII in memory consolidation and enhancement. Nature 2011;469:491-7. crossref(new window)

Nyberg F, Burman P. Growth hormone and its receptors in the central nervous system--location and functional significance. Horm Res 1996;45:18-22.

Pan W, Yu Y, Cain CM, Nyberg F, Couraud PO, Kastin AJ. Permeation of growth hormone across the blood-brain barrier. Endocrinology 2005;146:4898-904. crossref(new window)

Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, et al. GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 1998;396:674-9. crossref(new window)

Goudet C, Magnaghi V, Landry M, Nagy F, Gereau RWt, Pin JP. Metabotropic receptors for glutamate and GABA in pain. Brain Res Rev 2009;60:43-56. crossref(new window)

Benarroch EE. GABAB receptors: structure, functions, and clinical implications. Neurology 2012;78:578-84. crossref(new window)

Gronbladh A, Johansson J, Nyberg F, Hallberg M. Recombinant human growth hormone affects the density and functionality of GABAB receptors in the male rat brain. Neuroendocrinology 2013;97:203-11. crossref(new window)

Walser M, Hansen A, Svensson PA, Jernas M, Oscarsson J, Isgaard J, et al. Peripheral administration of bovine GH regulates the expression of cerebrocortical beta-globin, GABAB receptor 1, and the Lissencephaly-1 protein (LIS-1) in adult hypophysectomized rats. Growth Horm IGF Res 2011;21:16-24. crossref(new window)

Aberg ND, Carlsson B, Rosengren L, Oscarsson J, Isaksson OG, Ronnback L, et al. Growth hormone increases connexin- 43 expression in the cerebral cortex and hypothalamus. Endocrinology 2000;141:3879-86. crossref(new window)

Aramburo C, Alba-Betancourt C, Luna M, Harvey S. Expression and function of growth hormone in the nervous system: a brief review. Gen Comp Endocrinol 2014;203:35-42. crossref(new window)

Davies CH, Starkey SJ, Pozza MF, Collingridge GL. GABA autoreceptors regulate the induction of LTP. Nature 1991; 349:609-11. crossref(new window)

Gronbladh A, Johansson J, Nyberg F, Hallberg M. Administration of growth hormone and nandrolone decanoate alters mRNA expression of the GABA receptor subunits as well as of the GH receptor, IGF-1, and IGF-2 in rat brain. Growth Horm IGF Res 2014;24:60-6. crossref(new window)

Tu H, Xu C, Zhang W, Liu Q, Rondard P, Pin JP, et al. GABAB receptor activation protects neurons from apoptosis via IGF-1 receptor transactivation. J Neurosci 2010;30:749-59. crossref(new window)

Zhang F, Li C, Wang R, Han D, Zhang QG, Zhou C, et al. Activation of GABA receptors attenuates neuronal apoptosis through inhibiting the tyrosine phosphorylation of NR2A by Src after cerebral ischemia and reperfusion. Neuroscience 2007;150:938-49. crossref(new window)

Xu J, Li C, Yin XH, Zhang GY. Additive neuroprotection of GABA A and GABA B receptor agonists in cerebral ischemic injury via PI-3K/Akt pathway inhibiting the ASK1- JNK cascade. Neuropharmacology 2008;54:1029-40. crossref(new window)

Li CJ, Lu Y, Zhou M, et al. Activation of GABAB receptors ameliorates cognitive impairment via restoring the balance of HCN1/HCN2 surface expression in the hippocampal CA1 area in rats with chronic cerebral hypoperfusion. Mol Neurobiol 2014;50:704-20. crossref(new window)

Russo VC, Gluckman PD, Feldman EL, Werther GA. The insulin-like growth factor system and its pleiotropic functions in brain. Endocr Rev 2005;26:916-43. crossref(new window)

Rotwein P, Burgess SK, Milbrandt JD, Krause JE. Differential expression of insulin-like growth factor genes in rat central nervous system. Proc Natl Acad Sci U S A 1988;85:265-9. crossref(new window)

Alba-Betancourt C, Aramburo C, Avila-Mendoza J, Ahumada- Solórzano SM, Carranza M, Rodriguez-Mendez AJ, et al. Expression, cellular distribution, and heterogeneity of growth hormone in the chicken cerebellum during development. Gen Comp Endocrinol 2011;170:528-40. crossref(new window)

Carson MJ, Behringer RR, Brinster RL, McMorris FA. Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. Neuron 1993;10:729-40. crossref(new window)

Alba-Betancourt C, Luna-Acosta JL, Ramirez-Martinez CE, Avila-Gonzalez D, Granados-Avalos E, Carranza M, et al. Neuro-protective effects of growth hormone (GH) after hypoxia-ischemia injury in embryonic chicken cerebellum. Gen Comp Endocrinol 2013;183:17-31. crossref(new window)

Noguchi T, Sugiasaki T, Tsukada Y. Microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit). Neurochem Res 1985;10:1097-106. crossref(new window)