Lin Hsiao-Ju, Huang Chiung-Chun, Hsu Kuei-Sen
Department of Pharmacology, College of Medicine, Tainan, Taiwan.
Ann Neurol. 2006 Jun;59(6):939-51. doi: 10.1002/ana.20885.
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.
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.
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.
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.
合成糖皮质激素地塞米松（DEX）常被用作治疗药物以降低早产儿慢性肺病的发病率。令人惊讶的是，对于这种治疗的长期神经发育结局知之甚少。
我们采用与早产儿使用的类似的DEX递减剂量方案，研究了新生儿期DEX治疗对幼鼠海马突触可塑性及其后期联想记忆的影响。
新生儿期DEX治疗改变了突触可塑性的方向，有利于低频刺激诱导的长期抑制，并对抗青春期（5周龄）大鼠高频刺激诱导的长期增强，但这些改变在年轻成年（8周龄）大鼠中消失。发现DEX对长期抑制和长期增强的影响与钙/钙调蛋白依赖性蛋白激酶II自身磷酸化增加和蛋白磷酸酶1活性降低相关。新生儿期DEX治疗还破坏了接受被动回避学习任务的5周龄（而非8周龄）大鼠的记忆保持。
这些结果表明，新生儿期DEX治疗会改变后期生活中的海马突触可塑性和情境恐惧记忆形成，但这些损伤显然不是永久性的。
