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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

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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.

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  1. Klinik für Neurologie, Friedrich-Schiller-Universität Jena, 07740, Jena, Deutschland

    M. Schwab

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

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  • DOI: https://doi.org/10.1007/s00129-007-1969-8

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