Huang Chiung-Chun, Lin Hsiue-Ru, Liang Ying-Ching, Hsu Kuei-Sen
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan.
Pediatr Res. 2007 Sep;62(3):267-70. doi: 10.1203/PDR.0b013e318123f744.
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.
对于新生儿慢性肺病（CLD）采用皮质类固醇治疗后的长期神经发育结局，人们越来越关注。在此，我们采用一种方案，给予地塞米松（DEX）或氢化可的松（HC）的剂量逐渐减少，其比例与早产儿使用的剂量相当，以研究这些治疗对后期海马体突触可塑性和联想记忆的长期影响。我们发现，新生儿期DEX治疗而非HC治疗会损害青春期大鼠的长时程增强（LTP），但增强长时程抑制（LTD）的诱导。当在给予DEX之前给动物注射糖皮质激素受体拮抗剂RU38486时，可预防新生儿期DEX治疗对LTP和LTD的影响。我们还发现，新生儿期DEX治疗而非HC治疗会导致钙/钙调蛋白依赖性蛋白激酶II的一种异构体在苏氨酸-286处的自磷酸化显著增加，以及蛋白磷酸酶1表达减少。此外，仅新生儿期DEX治疗会破坏接受被动回避学习任务的大鼠的记忆保持。这些结果表明，仅新生儿期DEX治疗会改变后期海马体突触可塑性和联想记忆形成，因此提示在新生儿期治疗CLD时，HC可能是比DEX更安全的选择。
