Injectable dexamethasone administration enhances cortical GABAergic neuronal differentiation in a novel model of postnatal steroid therapy in mice.
Injectable dexamethasone (DXM) is widely used during the postnatal period in premature infants. However, this treatment has been associated with an increased incidence of neuromotor disorders. Few studies have directly addressed the impact of DXM therapy on neuronal differentiation. We used a murine model of postnatal steroid therapy in which mouse pups aged 3 and 4 postnatal days (P) received intraperitoneal injections of 1 mg . kg(-1) . 12 h(-1) of an injectable preparation that contained DXM and sulfites (DXM), pure DXM, or sulfites. The animals were weighed before they were killed on P5, P10, or P21, and their brains were investigated by immunohistochemistry with markers for neuronal differentiation. DXM administration was associated with a 20-30% reduction in body and brain weight gains and in cortical thickness on P5 and P10. gamma-Amino-butyric acid+ (GABA+) interneuron density was significantly increased (+50%) in the cerebral cortex of the animals given injectable DXM on P5 to P21 compared with controls (p < 0.01). In parallel, the density of cortical neurons expressing two interneuron markers (calbindin 28-kD and calretinin) increased significantly. These alterations occurred with injectable DXM but not with pure DXM or sulfites alone. In contrast, none of the study treatments modified the expression of other markers for neuronal transmission or axon myelination. In the animals that were given injectable DXM, cleaved caspase 3 antibody showed increased neuronal cell death, but calbindin antibody did not. In conclusion, in a murine model of postnatal steroid therapy, injectable DXM induced a selective increase in GABAergic neurons in the cerebral cortex.
Baud
Olivier
O
Laboratoire de Neurobiologie de Dévelopment, INSERM E9935, Paris, France. o.baud@rdb.ap-hop-paris.fr
Verney
Catherine
C
Evrard
Philippe
P
Gressens
Pierre
P
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D016923:Cell Death; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D013256:Steroids / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005938:Glucocorticoids; D013256:Steroids; D005680:gamma-Aminobutyric Acid; D003907:Dexamethasone