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Neonatal dexamethasone on day 7 causes mild hyperactivity and cerebellar stunting
1Division of Reproductive & Developmental Toxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. sferguson@nctr.fda.gov
Insights
Dexamethasone (DEX) exposure during early development impacts rat brain growth and behavior. Timing of DEX treatment is critical for central nervous system development outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Glucocorticoids are crucial for development but can disrupt it.
- Understanding the impact of synthetic glucocorticoids like dexamethasone (DEX) on the developing central nervous system (CNS) is vital.
Purpose of the Study:
- To examine how dexamethasone (DEX) administration at different early postnatal days affects CNS development in rats.
- To assess the long-term consequences of DEX on brain structure and neurobehavioral outcomes.
Main Methods:
- Rats received DEX (1-3 mg/kg) on postnatal day (PND) 3 or 7.
- Brain weight, DNA, and protein content were analyzed at various time points (PND 28, 84, 112).
- Neurobehavioral tests included nest odor preference, open field activity, running wheel activity, and maze performance.
Main Results:
- DEX treatment on PND 7 reduced brain and regional weights by PND 28, with partial recovery by PND 112.
- Hyperactivity was observed in rats treated with DEX on PND 7.
- Cerebellar and hippocampal development showed sensitivity to DEX exposure, with effects varying by treatment timing.
Conclusions:
- The timing of glucocorticoid exposure significantly influences the severity of CNS insults during development.
- Early-life DEX exposure can lead to lasting neurodevelopmental and behavioral changes.
- These findings highlight the critical developmental windows for brain vulnerability to glucocorticoids.
Abstract:
To investigate the effects of glucocorticoid treatment on central nervous system development, rats were injected with dexamethasone (DEX) (1-3 mg/kg) on postnatal day (PND) 3 or 7. DNA and protein content and concentration were measured in the cerebellum and hippocampus on PND 28 and 112. Whole and regional brain weights were measured at PND 28, 84, and 112. Nest odor preference (PND 10-11), open field activity (PND 18-21), running wheel activity (PND 50-56), and complex maze performance (PND 60-63) were measured in rats treated twice with 1.5 mg/kg DEX on PND 7. DEX treatment on PND 7 resulted in reductions in PND 28 whole brain and regional weights (frontal cortex, cerebellum, and brain stem) and, by PND 112, all except whole brain and cerebellar weights had recovered. A mild syndrome of hyperactivity (increased open field rearing and activity) was apparent in rats treated with DEX on PND 7. These results are discussed in terms of the developmental stage specificity in production of brain, and, specifically, cerebellar insults and their resulting effects.