Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys
1 Department of Neuroscience, Karolinska Institutet, S-171 77, Stockholm, Sweden
2 Stockholm Brain Institute, Sweden
3 Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, S-171 776, Stockholm, Sweden
4 Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany
5 Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology-Zurich, CH-8603 Schwerzenbach, Switzerland
6 Clinic for Affective Disorders and General Psychiatry, Psychiatric University Hospital Zurich, CH-8008 Zurich, Switzerland
Behavioral and Brain Functions 2010, 6:18 doi:10.1186/1744-9081-6-18Published: 22 March 2010
Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood.
In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy.
In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment.
These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences.