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Published on: August 25, 2014
Prenatal corticosteroid exposure alters early developmental seizures and behavior
1Department of Cell Biology & Anatomy, Department of Pediatrics, New York Medical College, 15 Dana Rd., Valhalla, NY, USA. Libor Velisek@nymc.edu
Insights
Prenatal corticosteroid exposure, like betamethasone, can alter seizure susceptibility and behaviors in offspring. Effects vary by corticosteroid type, impacting neurodevelopment and anxiety in young animals.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Prenatal corticosteroid administration is used to enhance lung development in preterm neonates.
- Maternal stress and corticosteroid exposure in pregnancy are linked to behavioral issues and potential epileptic spasms in children.
Purpose of the Study:
- To investigate the impact of prenatal corticosteroid exposure on postnatal seizure susceptibility and behavior in a rat model.
- To determine if different corticosteroids (hydrocortisone, betamethasone) have distinct effects on neurodevelopment and behavior.
Main Methods:
- Pregnant rats received hydrocortisone, betamethasone, or vehicle on gestational day 15.
- Seizures were induced on postnatal day 15 using flurothyl or kainic acid.
- Behavioral tests including horizontal bar holding and elevated plus maze were conducted.
Main Results:
- Betamethasone reduced susceptibility to flurothyl-induced seizures but not kainic acid-induced seizures.
- Hydrocortisone decreased postnatal weight but did not alter seizure susceptibility.
- Combined prenatal hydrocortisone and postnatal seizures increased anxiety; canrenoic acid amplified hydrocortisone's effects.
Conclusions:
- Prenatal corticosteroid exposure significantly alters postnatal seizure susceptibility and behavior.
- The specific effects on neurodevelopment and behavior are dependent on the type of corticosteroid administered.
Abstract:
In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2×10mg/kg), betamethasone (2×0.4mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species.
