Antenatal betamethasone treatment reduces synaptophysin immunoreactivity in presynaptic terminals in the fetal sheep brain

Knowledge of morphofunctional effects on the fetal brain induced by exogeno us glucocorticoids is limited. Recently, we reported alterations of both th e neuronal cytoskeleton and electrocortical function in the ovine fetal bra in after antenatal betamethasone treatment in doses used in perinatal medic ine. In the present study we examined whether these changes are accompanied by morphological alterations of synapses. Chronically instrumented fetal s heep at 0.87 of gestation were treated either with isotonic saline (n = 7) or 10 mug/h betamethasone (n = 7) over 48 h administered directly to the fe tal jugular vein. Paraffin sections of the frontal neocortex, caudate putam en and hippocampus were stained with a monoclonal antibody against synaptop hysin, a specific membrane protein of presynaptic vesicles and quantified m orphometrically. Synaptophysin-like immunoreactivity (synaptophysin-LI) sho wed a widespread granular pattern in the neuropil. Betamethasone exposure r educed synaptophysin-ll in the frontal neocortex, caudate putamen and hippo campus by 46.9, 41.0 and 55.4%, respectively, (P < 0.05) that was not accom panied by irreversible neuronal damage. These results suggest that clinical doses of betamethasone have acute effects on presynaptic terminals in the fetal sheep brain that could contribute to the altered complexity of electr ocortical function that we have shown previously to occur following fetal e xposure to betamethasone. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.