Neuropediatrics 2014; 45(06): 354-361
DOI: 10.1055/s-0034-1387167
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Effects of a Single Course of Prenatal Betamethasone on Dendritic Development in Dentate Gyrus Granular Neurons and on Spatial Memory in Rat Offspring

Carlos Bustamante
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
,
Martina Valencia
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
,
Christian Torres
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
,
María José González
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
,
Constanza Carvajal
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
,
Denisse Sandoval
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
,
Cristian Gutiérrez-Rojas
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
,
Rodrigo Pascual
1   Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
› Author Affiliations
Further Information

Publication History

26 January 2014

23 May 2014

Publication Date:
06 August 2014 (online)

Abstract

Background Preterm babies treated with synthetic glucocorticoids (sGC) in utero exhibit behavioral alterations and disturbances in brain maturation during infancy. However, the effects on dentate granule cell morphology and spatial memory in rats that were given clinically equivalent doses of antenatal betamethasone remain unclear.

Methods Pregnant rats were randomly divided into the following two experimental groups: control (CON) and betamethasone-treated (BET) groups. At gestational day 20 (G20), BET dams were subcutaneously injected with a 0.17 mg/kg betamethasone solution, and CON animals received a similar volume of saline. At postnatal days 22 (P22) and P52, BET and CON offsprings were behaviorally evaluated in the Y-Maze test, and the dentate gyrus granular neurons were histologically analyzed.

Results Animals prenatally treated with a single course of betamethasone exhibit a significant decrement in the dendritic outgrowth of dentate granule cells along with impaired spatial memory when evaluated at P52. Moreover, the body and brain weight of the BET group was significantly lower than the CON group at P0, P22, and P52.

Conclusion The current results indicate that a single course of betamethasone in pregnant rats produces significant neuronal and behavioral impairments of the offspring at adolescence along with a decrement in somatic and brain weights at each of the three ages evaluated.

 
  • References

  • 1 Sloviter RS, Sollas AL, Dean E, Neubort S. Adrenalectomy-induced granule cell degeneration in the rat hippocampal dentate gyrus: characterization of an in vivo model of controlled neuronal death. J Comp Neurol 1993; 330 (3) 324-336
  • 2 Rúa C, Trejo JL, Machín C, Arahuetes RM. Effects of maternal adrenalectomy and glucocorticoid administration on the development of rat hippocampus. J Hirnforsch 1995; 36 (4) 473-483
  • 3 Huang WL, Beazley LD, Quinlivan JA, Evans SF, Newnham JP, Dunlop SA. Effect of corticosteroids on brain growth in fetal sheep. Obstet Gynecol 1999; 94 (2) 213-218
  • 4 Antonow-Schlorke I, Schwab M, Li C, Nathanielsz PW. Glucocorticoid exposure at the dose used clinically alters cytoskeletal proteins and presynaptic terminals in the fetal baboon brain. J Physiol 2003; 547 (Pt 1) 117-123
  • 5 NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. Effect of corticosteroids for fetal maturation on perinatal outcomes. JAMA 1995; 273 (5) 413-418
  • 6 Modi N, Lewis H, Al-Naqeeb N, Ajayi-Obe M, Doré CJ, Rutherford M. The effects of repeated antenatal glucocorticoid therapy on the developing brain. Pediatr Res 2001; 50 (5) 581-585
  • 7 French NP, Hagan R, Evans SF, Godfrey M, Newnham JP. Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol 1999; 180 (1 Pt 1) 114-121
  • 8 Bruschettini M, van den Hove DL, Timmers S , et al. Cognition- and anxiety-related behavior, synaptophysin and MAP2 immunoreactivity in the adult rat treated with a single course of antenatal betamethasone. Pediatr Res 2006; 60 (1) 50-54
  • 9 Noorlander CW, Visser GH, Ramakers GM, Nikkels PG, de Graan PN. Prenatal corticosteroid exposure affects hippocampal plasticity and reduces lifespan. Dev Neurobiol 2008; 68 (2) 237-246
  • 10 Liu L, Li A, Matthews SG. Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects. Am J Physiol Endocrinol Metab 2001; 280 (5) E729-E739
  • 11 Owen D, Matthews SG. Glucocorticoids and sex-dependent development of brain glucocorticoid and mineralocorticoid receptors. Endocrinology 2003; 144 (7) 2775-2784
  • 12 Kellendonk C, Gass P, Kretz O, Schütz G, Tronche F. Corticosteroid receptors in the brain: gene targeting studies. Brain Res Bull 2002; 57 (1) 73-83
  • 13 Hosseini-Sharifabad M, Hadinedoushan H. Prenatal stress induces learning deficits and is associated with a decrease in granules and CA3 cell dendritic tree size in rat hippocampus. Anat Sci Int 2007; 82 (4) 211-217
  • 14 Bustamante C, Bilbao P, Contreras W , et al. Effects of prenatal stress and exercise on dentate granule cells maturation and spatial memory in adolescent mice. Int J Dev Neurosci 2010; 28 (7) 605-609
  • 15 Scheepens A, van de Waarenburg M, van den Hove D, Blanco CE. A single course of prenatal betamethasone in the rat alters postnatal brain cell proliferation but not apoptosis. J Physiol 2003; 552 (Pt 1) 163-175
  • 16 Sánchez C, Díaz-Nido J, Avila J. Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog Neurobiol 2000; 61 (2) 133-168
  • 17 Barros VG, Duhalde-Vega M, Caltana L, Brusco A, Antonelli MC. Astrocyte-neuron vulnerability to prenatal stress in the adult rat brain. J Neurosci Res 2006; 83 (5) 787-800
  • 18 Vivar C, van Praag H. Functional circuits of new neurons in the dentate gyrus. Front Neural Circuits 2013; 7 (15) 1-13
  • 19 Krueppel R, Remy S, Beck H. Dendritic integration in hippocampal dentate granule cells. Neuron 2011; 71 (3) 512-528
  • 20 Conrad CD, Grote KA, Hobbs RJ, Ferayorni A. Sex differences in spatial and non-spatial Y-maze performance after chronic stress. Neurobiol Learn Mem 2003; 79 (1) 32-40
  • 21 Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 4th ed.. New York, NY: Academic Press; 1998
  • 22 Redila VA, Christie BR. Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus. Neuroscience 2006; 137 (4) 1299-1307
  • 23 You JM, Yun SJ, Nam KN, Kang C, Won R, Lee EH. Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures. Can J Physiol Pharmacol 2009; 87 (6) 440-447
  • 24 Gao X, Smith GM, Chen J. Impaired dendritic development and synaptic formation of postnatal-born dentate gyrus granular neurons in the absence of brain-derived neurotrophic factor signaling. Exp Neurol 2009; 215 (1) 178-190
  • 25 Rihn LL, Claiborne BJ. Dendritic growth and regression in rat dentate granule cells during late postnatal development. Brain Res Dev Brain Res 1990; 54 (1) 115-124
  • 26 Tijsseling D, Wijnberger LD, Derks JB , et al. Effects of antenatal glucocorticoid therapy on hippocampal histology of preterm infants. PLoS ONE 2012; 7 (3) e33369
  • 27 Davis EP, Sandman CA, Buss C, Wing DA, Head K. Fetal glucocorticoid exposure is associated with preadolescent brain development. Biol Psychiatry 2013; 74 (9) 647-655
  • 28 Mainen ZF, Sejnowski TJ. Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 1996; 382 (6589) 363-366
  • 29 Spear LP, Brake SC. Periadolescence: age-dependent behavior and psychopharmacological responsivity in rats. Dev Psychobiol 1983; 16 (2) 83-109
  • 30 Khalife N, Glover V, Taanila A, Ebeling H, Järvelin MR, Rodriguez A. Prenatal glucocorticoid treatment and later mental health in children and adolescents. PLoS ONE 2013; 8 (11) e81394
  • 31 Moss TJ, Doherty DA, Nitsos I, Sloboda DM, Harding R, Newnham JP. Effects into adulthood of single or repeated antenatal corticosteroids in sheep. Am J Obstet Gynecol 2005; 192 (1) 146-152
  • 32 Murphy KE, Willan AR, Hannah ME , et al; Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study Collaborative Group. Effect of antenatal corticosteroids on fetal growth and gestational age at birth. Obstet Gynecol 2012; 119 (5) 917-923
  • 33 Norberg H, Stålnacke J, Diaz Heijtz R , et al. Antenatal corticosteroids for preterm birth: dose-dependent reduction in birthweight, length and head circumference. Acta Paediatr 2011; 100 (3) 364-369
  • 34 Davis EP, Waffarn F, Uy C, Hobel CJ, Glynn LM, Sandman CA. Effect of prenatal glucocorticoid treatment on size at birth among infants born at term gestation. J Perinatol 2009; 29 (11) 731-737
  • 35 Price WA, Stiles AD, Moats-Staats BM, D'Ercole AJ. Gene expression of insulin-like growth factors (IGFs), the type 1 IGF receptor, and IGF-binding proteins in dexamethasone-induced fetal growth retardation. Endocrinology 1992; 130 (3) 1424-1432
  • 36 Uno H, Lohmiller L, Thieme C , et al. Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques. I. Hippocampus. Brain Res Dev Brain Res 1990; 53 (2) 157-167
  • 37 Spinillo A, Viazzo F, Colleoni R, Chiara A, Maria Cerbo R, Fazzi E. Two-year infant neurodevelopmental outcome after single or multiple antenatal courses of corticosteroids to prevent complications of prematurity. Am J Obstet Gynecol 2004; 191 (1) 217-224