the role of growth retardation in lasting effects of neonatal dexamethasone treatment on hippocampal synaptic function生长迟缓的作用持久的新生儿地塞米松治疗海马突触功能的影响.pdfVIP

The Role of Growth Retardation in Lasting Effects of Neonatal Dexamethasone Treatment on Hippocampal Synaptic Function 1 1 1,2 Yu-Chen Wang , Chiung-Chun Huang , Kuei-Sen Hsu * 1 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, 2 Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan, Taiwan Abstract Background: Dexamethasone (DEX), a synthetic glucocorticoid, is commonly used to prevent or lessen the morbidity of chronic lung disease in preterm infants. However, evidence is now increasing that this clinical practice negatively affects somatic growth and may result in long-lasting neurodevelopmental deficits. We therefore hypothesized that supporting normal somatic growth may overcome the lasting adverse effects of neonatal DEX treatment on hippocampal function. Methodology/Principal Findings: To test this hypothesis, we developed a rat model using a schedule of tapering doses of DEX similar to that used in premature infants and examined whether the lasting influence of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance are correlated with the deficits in somatic growth. We confirmed that neonatal DEX treatment switched the direction of synaptic plasticity in hippocampal CA1 region, favoring low- frequency stimulation- and group I metabotropic glutamate receptor agonist (S)-3,5,-dihydroxyphenylglycine-induced long- term depression (LTD), and opposing the induction of long-term potentiation (LTP) by high-frequency stimulation in the adolescent period. The effects of DEX on LTP and LTD were correlated with an increase in the autophosphorylation of Ca2+/ calmodulin-dependent protein kinase II at threonine-286 and a decrease in the