Effects of neonatal dexamethasone treatment on hippocampal synaptic function.
OBJECTIVE
Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Surprisingly, little is known about the long-term neurodevelopmental outcomes of this therapy.


METHODS
Using a schedule of tapering doses of DEX similar to that used in premature infants, we examined the consequences of neonatal DEX treatment on hippocampal synaptic plasticity of infants and associative memory later in their lives.


RESULTS
Neonatal DEX treatment changed the direction of synaptic plasticity, favoring low-frequency, stimulation-induced, long-term depression and opposing the induction of long-term potentiation by high-frequency stimulation in adolescent (5-week-old) rats, but these alterations disappeared in young adult (8-week-old) rats. The effects of DEX on long-term depression and long-term potentiation were found to correlate with an increase in the autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase II and a decrease in the protein phosphatase 1 activity. Neonatal DEX treatment also disrupted memory retention in 5-week-old (but not 8-week-old) rats subjected to passive avoidance learning tasks.


CONCLUSIONS
These results suggest that neonatal DEX treatment alters hippocampal synaptic plasticity and contextual fear memory formation in later life, but these impairments apparently are not permanent.
Lin
Hsiao-Ju
HJ
Department of Pharmacology, College of Medicine, Tainan, Taiwan.
Huang
Chiung-Chun
CC
Hsu
Kuei-Sen
KS
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009924:Organ Culture Techniques; D010749:Phosphoprotein Phosphatases / Q000187:drug effects / Q000378:metabolism; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D054645:Protein Phosphatase 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D005938:Glucocorticoids; D003907:Dexamethasone; D011494:Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1