Antenatal betamethasone treatment reduces synaptophysin immunoreactivity in presynaptic terminals in the fetal sheep brain.
Knowledge of morphofunctional effects on the fetal brain induced by exogenous glucocorticoids is limited. Recently, we reported alterations of both the neuronal cytoskeleton and electrocortical function in the ovine fetal brain after antenatal betamethasone treatment in doses used in perinatal medicine. In the present study we examined whether these changes are accompanied by morphological alterations of synapses. Chronically instrumented fetal sheep at 0.87 of gestation were treated either with isotonic saline (n=7) or 10 microg/h betamethasone (n=7) over 48 h administered directly to the fetal jugular vein. Paraffin sections of the frontal neocortex, caudate putamen and hippocampus were stained with a monoclonal antibody against synaptophysin, a specific membrane protein of presynaptic vesicles and quantified morphometrically. Synaptophysin-like immunoreactivity (synaptophysin-LI) showed a widespread granular pattern in the neuropil. Betamethasone exposure reduced synaptophysin-LI in the frontal neocortex, caudate putamen and hippocampus by 46.9, 41.0 and 55.4%, respectively, (P<0.05) that was not accompanied 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 electrocortical function that we have shown previously to occur following fetal exposure to betamethasone.
Antonow-Schlorke
I
I
Department of Neurology, Friedrich Schiller University Jena, D-07740, Jena, Germany.
Kühn
B
B
Müller
T
T
Schubert
H
H
Sliwka
U
U
Nathanielsz
P W
PW
Schwab
M
M
D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005333:Fetus; D005625:Frontal Lobe / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D012756:Sheep; D016708:Synaptophysin / Q000378:metabolism*
D016708:Synaptophysin; D001623:Betamethasone