Effects of neonatal corticosteroid treatment on hippocampal synaptic function.
There is growing concern about long-term neurodevelopmental outcomes after neonatal corticosteroid treatment for chronic lung disease (CLD). Here, we use a protocol with tapering doses of dexamethasone (DEX) or hydrocortisone (HC) proportional to those used in preterm infants to examine the long-term consequences of these treatments on hippocampal synaptic plasticity and associative memory in later life. We found that neonatal DEX, but not HC, treatment impairs long-term potentiation (LTP) but enhances long-term depression (LTD) induction in adolescent rats. The effects of neonatal DEX treatment on LTP and LTD were prevented when the animals were given glucocorticoid receptor antagonist, RU38486, before DEX administration. We also found that neonatal DEX, but not HC, treatment induces a profound increase in the autophosphorylation of a isoform of Ca2+/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. In addition, only neonatal DEX treatment disrupts memory retention in rats subjected to passive avoidance learning tasks. These results demonstrate that only neonatal DEX treatment alters the hippocampal synaptic plasticity and associative memory formation in later life and thus suggest that HC may be a safer alternative to DEX for the treatment of CLD in the neonatal period.
Huang
Chiung-Chun
CC
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan.
Lin
Hsiue-Ru
HR
Liang
Ying-Ching
YC
Hsu
Kuei-Sen
KS
D000293:Adolescent; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001362:Avoidance Learning / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004594:Electrophysiology; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology* / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008171:Lung Diseases / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone; D003907:Dexamethasone; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D006854:Hydrocortisone