Skip to main content

Fetale Hirnentwicklung und Programmierung von zerebralen Funktionsstörungen

Einfluss von pränataler Mangelernährung, Stress und Glukokortikoiden

Fetal brain development and the programming of cerebral disorders

Effects of prenatal malnutrition, stress and glucocorticoids

Zusammenfassung

Epigenetische Einflüsse, insbesondere solche, die mit einer fetalen Mangelversorgung oder erhöhten fetalen Stresshormonkonzentrationen einhergehen, scheinen eine größere Rolle bei der Entwicklung der fetalen Hirnfunktion zu spielen als angenommen. Schon eine moderate Mangelernährung hat einen direkten Effekt auf die strukturelle und funktionelle Hirnentwicklung und führt zu einer Erhöhung von mütterlichen Stresshormonkonzentrationen im fetalen Kreislauf. Auch erhöhte fetale Stresshormonkonzentrationen führen zu Störungen der strukturellen und funktionellen Hirnentwicklung. Erhöhte Stresshormonkonzentrationen in den letzten Wochen der Schwangerschaft induzieren aufgrund einer dauerhaften Desensitivierung von Glukokortikoidrezeptoren im Hippocampus eine verminderte negative Rückkopplung der HHN-Achse mit der Folge einer verstärkten Kortisolausschüttung und einer erhöhten Stressempfindlichkeit im späteren Leben. Die Hyperaktivität der Stressachse bewirkt Störungen der Aktivität von Neurotransmittersystemen und eine Verschlechterung des Schlaganfalloutcomes.

Abstract

Epigenetic influences during intrauterine life seem to play a larger part in the development of the fetal brain than was hitherto assumed, those associated with fetal malnutrition and enhanced stress hormone levels having the most pronounced effects on brain function in later life. Even modest malnutrition has direct effects on structural and functional brain development and leads to enhanced concentrations of maternal stress hormones in the fetal circulation. Increased fetal cortisol concentrations also lead to impaired structural and functional brain development. Elevated cortisol concentrations during the last weeks of pregnancy induce permanent desensitization of glucocorticoid receptors in the hippocampus, with a consequent decline in negative feedback regulation of the HPA axis; the result is enhanced cortisol excretion and elevated susceptibility to stress in later life. Hyperactivity of the stress axis leads to impaired activity of the neurotransmitter systems and makes for a poor prognosis in the event of stroke.

This is a preview of subscription content, access via your institution.

Abb. 1

Literatur

  1. 1.

    Brand SR, Engel SM, Canfield R L et al. (2006)The effect of maternal PTSD following in utero trauma exposure on behavior and temperament in the 9-month-old infant. Ann N Y Acad Sci 1071: 454–458

    Article  PubMed  Google Scholar 

  2. 2.

    Collaborative Group on Antenatal Steroid Therapy (1984) Effects of antenatal dexamethasone administration in the infant: long-term follow-up. J Pediatr 104: 259–267

    PubMed  Google Scholar 

  3. 3.

    Dalziel SR, Lim VK, Lambert A et al. (2005) Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ 331: 665–668

    Article  PubMed  Google Scholar 

  4. 4.

    Dessens AB, Haas HS, Koppe JG (2000) Twenty-year follow-up of antenatal corticosteroid treatment. Pediatrics 105: E77

    Article  PubMed  Google Scholar 

  5. 5.

    French NP, Hagan R, Evans SF et al. (2005) Repeated antenatal corticoisteroids: effects on cerebral palsy and childhood behaviour. Am J Obstet Gynecol 190: 588–595

    Article  Google Scholar 

  6. 6.

    Hanley NR, Van de Kar LD (2003) Serotonin and the neuroendocrine regulation of the hypothalamic-pituitary-adrenal axis in health and disease. Vitam Horm 66: 189–255

    PubMed  Google Scholar 

  7. 7.

    Huizink AC, Mulder EJ, Buitelaar JK (2004) Prenatal stress and risk for psychopathology: specific effects or induction of general susceptibility? Psychol Bull 130: 115–142

    Article  PubMed  Google Scholar 

  8. 8.

    Kyle UG, Pichard C (2006) The Dutch famine of 1944–1945: a pathophysiological model of long-term consequences of wasting disease. Curr Opin Clin Nutr Metab Care 9: 388–394

    PubMed  Google Scholar 

  9. 9.

    Lemaire V, Koehl M, Le Moal M et al. (2000) Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci USA 97: 11032–11037

    Article  PubMed  Google Scholar 

  10. 10.

    Leonard BE (2005) The HPA and immune axes in stress: the involvement of the serotonergic system. Eur Psychiatry 20: S302–S306

    Article  PubMed  Google Scholar 

  11. 11.

    MacArthur BA, Howie RN, DeZoete JA et al. (1982) School progress and cognitive development of 6-year old children whose mothers were treated antenatally with betamethasone. Pediatrics 70: 99–105

    PubMed  Google Scholar 

  12. 12.

    Matte TD, Bresnahan M, Begg MD et al. (2001) Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study. Br Med J 323: 310–314

    Article  Google Scholar 

  13. 13.

    Matthews SG (2001) Antenatal glucocorticoids and the developing brain: mechanisms of action. Semin Neonatol 6: 309–317

    Article  PubMed  Google Scholar 

  14. 14.

    McMillen IC, Robinson JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85: 571–633

    Article  PubMed  Google Scholar 

  15. 15.

    Meyer-Bahlburg HF, Dolezal C, Baker SW et al. (2004) Cognitive and motor development of children with and without congenital adrenal hyperplasia after early-prenatal dexamethasone. J Clin Endocrinol Metab 89: 610–614

    Article  PubMed  Google Scholar 

  16. 16.

    Morgane PJ, Mokler DJ, Galler JR (2002) Effects of prenatal protein malnutrition on the hippocampal formation. Neurosci Biobehav Rev 26: 471–483

    Article  PubMed  Google Scholar 

  17. 17.

    Olness K (2003) Effects on brain development leading to cognitive impairment: a worldwide epidemic. J Dev Behav Pediatr 24: 120–130

    PubMed  Google Scholar 

  18. 18.

    Richards M, Hardy R, Kuh D et al. (2002) Birthweight, postnatal growth and cognitive function in a national UK birth cohort. Int J Epidemiol 31: 342–348

    Article  PubMed  Google Scholar 

  19. 19.

    Sapolsky RM, Pulsinelli WA (1985) Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications. Science 229: 1397–1400

    Article  PubMed  Google Scholar 

  20. 20.

    Schmand B, Neuvel J, Smolders-deHaas H et al. (1990) Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. Pediatrics 86: 58–64

    PubMed  Google Scholar 

  21. 21.

    Sloboda DM, Challis JR, Moss TJ et al. (2005) Synthetic glucocorticoids: antenatal administration and long-term implications. Curr Pharm Des 11: 1459–1472

    Article  PubMed  Google Scholar 

  22. 22.

    Sontag LW (1941) The significance of environmental differences. Am J Obstet Gynecol 42: 996–1003

    Google Scholar 

  23. 23.

    St Clair D, Xu M, Wang P et al. (2005) Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. JAMA 294: 557–562

    Article  PubMed  Google Scholar 

  24. 24.

    Sugo N, Hurn PD, Morahan MB et al. (2002) Social stress exacerbates focal cerebral ischemia in mice. Stroke 33: 1660–1664

    Article  PubMed  Google Scholar 

  25. 25.

    Thakur A, Sase M, Lee JJ et al. (2000) Effect of dexamethasone on insulin-like growth factor-1 expression in a rabbit model of growth retardation. J Pediatr Surg 35: 898–904

    Article  PubMed  Google Scholar 

  26. 26.

    Thompson C, Syddall H, Rodin I et al. (2001) Birth weight and the risk of depressive disorder in late life. Br J Psychiatry 179: 450–455

    Article  PubMed  Google Scholar 

  27. 27.

    Van den Bergh BR, Mulder EJ, Mennes M et al. (2005) Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev 29: 237–258

    Article  PubMed  Google Scholar 

  28. 28.

    Vythilingam M, Vermetten E, Anderson GM et al. (2004) Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiatry 56: 101–112

    Article  PubMed  Google Scholar 

  29. 29.

    Weinstock M (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65: 427–451

    Article  PubMed  Google Scholar 

  30. 30.

    Welberg LA, Seckl JR (2001) Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 13: 113–128

    Article  PubMed  Google Scholar 

  31. 31.

    Yeh TF, Lin YJ, Lin HC et al. (2004) Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 350: 1304–1313

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Author information

Affiliations

Authors

Corresponding author

Correspondence to M. Schwab.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schwab, M. Fetale Hirnentwicklung und Programmierung von zerebralen Funktionsstörungen. Gynäkologe 40, 256–263 (2007). https://doi.org/10.1007/s00129-007-1969-8

Download citation

Schlüsselwörter

  • Pränatale Mangelernährung
  • Pränataler Stress
  • Glukokortikoide
  • Fetale Programmierung
  • Gehirn

Keywords

  • Prenatal malnutrition
  • Prenatal stress
  • Glucocorticoids
  • Fetal programming
  • Brain