角色扮演
奶油
内分泌学
蛋白激酶A
内科学
记忆巩固
莫里斯水上航行任务
睡眠剥夺
海马结构
PDE10A型
磷酸二酯酶抑制剂
快速眼动睡眠
化学
磷酸二酯酶
神经科学
海马体
心理学
药理学
医学
磷酸化
酶
昼夜节律
生物化学
眼球运动
基因
转录因子
作者
Ahmed Maher,Nesrine S. El Sayed,Heba Nafea,Mohamed Z. Gad
出处
期刊:Cns & Neurological Disorders-drug Targets
[Bentham Science]
日期:2022-08-01
卷期号:21 (7): 631-639
被引量:9
标识
DOI:10.2174/1871527320666210816105144
摘要
Background: Over the last few years, the number of people suffering from sleeping disorders has increased significantly despite negative effects on cognition and an association with brain inflammation. Objectives: We assessed memory deficits caused by Sleep Deprivation (SD) to determine the therapeutic effect of phosphodiesterase 4 (PDE4) inhibitors on SD-induced memory deficits and to investigate whether the modulation of memory deficits by PDE4 inhibitors is mediated by a protein kinase A (PKA)-independent pathway in conjunction with a PKA-dependent pathway. Methods: Adult male mice were divided into four groups. Three SD groups were deprived of Rapid Eye Movement (REM) sleep for 12 h a day for six consecutive days. They were tested daily in the Morris water maze to evaluate learning and memory. One of the SD groups was injected with a PDE4 inhibitor, rolipram (1 mg/kg ip), whereas another had rolipram co-administered with chlorogenic acid (CHA, 20 mg/kg ip), an inhibitor of PKA. After 6 days, the mice were sacrificed, and the hippocampi were evaluated for cyclic AMP (cAMP) and nuclear factor Nrf-2 levels. The hippocampal expression of PKA, phosphorylated cAMP Response Element-Binding Protein (CREB), and phosphorylated glycogen synthase 3β (Ser389) were also evaluated. Results: SD caused a significant decrease in cAMP levels in the brain and had a detrimental effect on learning and memory. The administration of rolipram or rolipram+CHA resulted in an improvement in cognitive function. Conclusion: The present study provides evidence that restoration of memory with PDE4 inhibitors occurs through a dual mechanism involving the PKA and Epac pathways.
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