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Early handling modulates outcome of neonatal dexamethasone exposure
Sanne E F Claessens1, Nikolaos P Daskalakis, Melly S Oitzl
1Division of Medical Pharmacology, LACDR/LUMC, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. s.e.f.claessens@gmail.com
Insights
Neonatal handling, which enhances maternal care, can mitigate some adverse neurodevelopmental effects of dexamethasone (DEX) treatment in infant rats, improving adult behavioral outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Synthetic glucocorticoids like dexamethasone (DEX) treat infant respiratory issues but can cause neurodevelopmental harm.
- Maternal care positively influences neurodevelopment in rodent models.
- Neonatal handling is a method to increase maternal care.
Purpose of the Study:
- To investigate if neonatal handling can counteract adverse neurodevelopmental effects of early-life dexamethasone (DEX) exposure.
- To assess the impact of handling and DEX on the endocrine and behavioral development of male rats.
Main Methods:
- Neonatal male rats received either DEX treatment or handling (or both) during early life.
- Maternal care was observed, and developmental milestones (eye opening, body weight) were recorded.
- Adult behavioral tests included spatial learning (T-maze, water maze), fear acquisition, startle reactivity, and pre-pulse inhibition.
Main Results:
- Handling increased maternal care; DEX accelerated eye opening and reduced body weight.
- Handling ameliorated DEX-induced spatial learning deficits and reduced susceptibility in the water maze.
- Handling, but not DEX alone, reduced fear acquisition; handling improved pre-pulse inhibition impaired by DEX.
Conclusions:
- Neonatal handling enhances maternal care and significantly attenuates specific DEX-induced neurodevelopmental alterations.
- Early-life handling may serve as a protective intervention against the long-term behavioral consequences of synthetic glucocorticoid exposure.
Abstract:
Synthetic glucocorticoids such as dexamethasone (DEX) are used to prevent or treat respiratory disorders in prematurely born infants. Besides the short-term benefit on lung development, numerous human and animal studies have reported adverse neurodevelopmental side effects. In contrast, maternal care is known to exert a positive influence on neurodevelopmental outcome in rodents. The aim of the current study was therefore to investigate whether neonatal handling (days 1-21), known to induce maternal care, might serve as an intervention strategy modulating the adverse effects of DEX treatment (days 1-3). For this purpose we have measured the outcome of these early-life manipulations on development as well as adult endocrine and behavioral phenotype of male rats. Maternal care was observed during the first week of life and indeed enhanced in response to handling. Eye opening was accelerated and body weight reduced in DEX-treated animals. In adulthood, we report that handling ameliorated impaired spatial learning observed in DEX treated non-handled animals in the T-maze. Additionally, handling reduced susceptibility to the impact of DEX treatment in the water maze. Although DEX treatment and handling both resulted in enhanced negative feedback of the stress-induced corticosterone response and both reduced startle reactivity, the acquisition of fear was only reduced by handling, without effect of DEX. Interestingly, handling had a beneficial effect on pre-pulse inhibition, which was diminished after DEX treatment. In conclusion, these findings indicate that handling of the neonate enhances maternal care and attenuates specific DEX-induced alterations in the adult behavioral phenotype.
